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Diehl, Louis Frederic

Overview:

Research interests include Hodgkin disease, non-Hodgkin lymphomas, Chronic Lymphocytic Leukemia, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, Myelodysplasia.

Positions:

Professor of Medicine

Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1975

M.D. — Georgetown University

Medical Resident, Medicine

Walter Reed Army Medical Center

Fellow In Hematology Oncology, Medicine

Walter Reed Army Medical Center

News:

Publications:

(18)F-fluorodeoxyglucose-positron emission tomography/computed tomography after one cycle of chemotherapy in patients with diffuse large B-cell lymphoma: results of a Nordic/US intergroup study.

We evaluated the predictive value of interim positon emission tomography (I-PET) after one course of chemoimmunotherapy in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). One hundred and twelve patients with DLBCL were enrolled. All patients had PET/computed tomography (CT) scans performed after one course of chemotherapy (PET-1). I-PET scans were categorized according to International Harmonization Project criteria (IHP), Deauville 5-point scale (D 5PS) with scores 1-3 considered negative (D 5PS > 3) and D 5PS with scores 1-4 considered negative (D 5PS = 5). Ratios of tumor maximum standardized uptake value (SUVmax) to liver SUVmax were also analyzed. We found no difference in progression-free survival (PFS) between PET-negative and PET-positive patients according to IHP and D 5PS > 3. The 2-year PFS using D 5PS = 5 was 50.9% in the PET-positive group and 84.8% in the PET-negative group (p = 0.002). A tumor/liver SUVmax cut-off of 3.1 to distinguish D 5PS scores of 4 and 5 provided the best prognostic value. PET after one course of chemotherapy was not able to safely discriminate PET-positive and PET-negative patients in different prognostic groups.

Authors
Mylam, KJ; Kostakoglu, L; Hutchings, M; Coleman, M; Lamonica, D; Czuczman, MS; Diehl, LF; Nielsen, AL; Jensen, P; Loft, A; Hendel, HW; Iyer, V; Leppä, S; Jyrkkiö, S; Holte, H; Eriksson, M; Gillstrøm, D; Hansen, PB; Seppänen, M; Hjorthaug, K; Brown, PDN; Pedersen, LM
MLA Citation
Mylam, KJ, Kostakoglu, L, Hutchings, M, Coleman, M, Lamonica, D, Czuczman, MS, Diehl, LF, Nielsen, AL, Jensen, P, Loft, A, Hendel, HW, Iyer, V, Leppä, S, Jyrkkiö, S, Holte, H, Eriksson, M, Gillstrøm, D, Hansen, PB, Seppänen, M, Hjorthaug, K, Brown, PDN, and Pedersen, LM. "(18)F-fluorodeoxyglucose-positron emission tomography/computed tomography after one cycle of chemotherapy in patients with diffuse large B-cell lymphoma: results of a Nordic/US intergroup study." Leukemia & lymphoma 56.7 (July 2015): 2005-2012.
PMID
25330442
Source
epmc
Published In
Leukemia & Lymphoma (Informa)
Volume
56
Issue
7
Publish Date
2015
Start Page
2005
End Page
2012
DOI
10.3109/10428194.2014.975800

Low-dose consolidation radiation therapy for early stage unfavorable Hodgkin lymphoma.

PURPOSE: The German Hodgkin Study Group (GHSG) trial HD11 established 4 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and 30 Gy of radiation therapy (RT) as a standard for early stage (I, II), unfavorable Hodgkin lymphoma (HL). Additional cycles of ABVD may allow for a reduction in RT dose and improved toxicity profile. METHODS AND MATERIALS: Patients treated with combined modality therapy at the Duke Cancer Institute for early stage, unfavorable HL by GHSG criteria from 1994 to 2012 were included. Patients who did not undergo post-chemotherapy functional imaging (positron emission tomography or gallium imaging) or who failed to achieve a complete response were excluded. Clinical outcomes were estimated using the Kaplan-Meier method. Late effects were also evaluated. RESULTS: A total of 90 patients met inclusion criteria for analysis. Median follow-up was 5 years. Chemotherapy consisted primarily of ABVD (88%) with a median number of 6 cycles. The median dose of consolidation RT was 23.4 Gy. Four patients had relapses, 2 of which were in-field. Ten-year progression-free survival (PFS) and overall survival (OS) were 93% (95% confidence interval [CI]: 0.82-0.97) and 98% (95% CI: 0.92-0.99), respectively. For the subset of patients (n=46) who received 5 to 6 cycles of chemotherapy and ≤ 24 Gy, the 10-year PFS and OS values were 88% (95% CI: 70%-96%) and 98% (95% CI: 85% - 99%), respectively. The most common late effect was hypothyroidism (20%) with no cardiac complications. Seven secondary malignancies were diagnosed, with only 1 arising within the RT field. CONCLUSIONS: Lower doses of RT may be sufficient when combined with more than 4 cycles of ABVD for early stage, unfavorable HL and may result in a more favorable toxicity profile than 4 cycles of ABVD and 30 Gy of RT.

Authors
Torok, JA; Wu, Y; Prosnitz, LR; Kim, GJ; Beaven, AW; Diehl, LF; Kelsey, CR
MLA Citation
Torok, JA, Wu, Y, Prosnitz, LR, Kim, GJ, Beaven, AW, Diehl, LF, and Kelsey, CR. "Low-dose consolidation radiation therapy for early stage unfavorable Hodgkin lymphoma." International journal of radiation oncology, biology, physics 92.1 (May 2015): 54-59.
PMID
25863754
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
92
Issue
1
Publish Date
2015
Start Page
54
End Page
59
DOI
10.1016/j.ijrobp.2015.02.003

Peripheral T-cell lymphoma, NOS, and anaplastic large cell lymphoma.

Peripheral T-cell lymphomas (PTCL), with the exception of anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL), have a very poor prognosis. Although current first line chemotherapy continues to be a CHOP-like (cyclophosphamide, doxorubicin, vincristine, prednisone) regimen there is now data suggesting that the addition of etoposide in younger patients improves outcomes. Even for those patients who do have a response to therapy, the risk of relapse remains quite high. Although autologous transplant in first remission is often used, its role as consolidation therapy in first remission remains unclear and may preferentially benefit low-risk patients. In the relapsed setting, major advances have occurred with Food and Drug Administration (FDA) approval of 4 new agents (pralatrexate, romidepsin, belinostat, brentuximab vedotin) for relapsed/refractory PTCL since 2009. These 4 drugs represent the first agents ever approved specifically for this indication. Unfortunately, with the exception of ALCL for which brentuximab vedotin will likely substantially change our approach to treatment, there are still many patients for whom available drugs will not be effective, and it is for these patients that further advances are urgently needed.

Authors
Beaven, AW; Diehl, LF
MLA Citation
Beaven, AW, and Diehl, LF. "Peripheral T-cell lymphoma, NOS, and anaplastic large cell lymphoma." Hematology. American Society of Hematology. Education Program 2015 (January 2015): 550-558.
PMID
26637771
Source
epmc
Published In
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program
Volume
2015
Publish Date
2015
Start Page
550
End Page
558
DOI
10.1182/asheducation-2015.1.550

Improving outcomes in advanced DLBCL: systemic approaches and radiotherapy.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Approximately half of patients will present with advanced (stage III/IV) disease. The cornerstone of treatment is a combination of chemotherapy and immunotherapy, most commonly R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Efforts to improve upon R-CHOP-including more chemotherapy cycles, dose-dense chemotherapy, alternative drug combinations, high-dose chemotherapy with autologous stem cell transplant, and maintenance rituximab-have generally proved unsuccessful. There is a growing body of retrospective and prospective data, however, suggesting a benefit for consolidation radiation therapy (RT) in select patients with advanced DLBCL. Consolidation RT has been shown to improve outcomes for patients with advanced DLBCL generally, and in specific instances including initially bulky disease, bone involvement, or in the setting of a partial response to systemic therapy. In these settings consolidation RT is highly efficacious at achieving local disease control and improving overall outcomes.

Authors
Boyle, J; Beaven, AW; Diehl, LF; Prosnitz, LR; Kelsey, CR
MLA Citation
Boyle, J, Beaven, AW, Diehl, LF, Prosnitz, LR, and Kelsey, CR. "Improving outcomes in advanced DLBCL: systemic approaches and radiotherapy." Oncology (Williston Park, N.Y.) 28.12 (December 2014): 1074-1084.
PMID
25510806
Source
epmc
Published In
Oncology
Volume
28
Issue
12
Publish Date
2014
Start Page
1074
End Page
1084

In vivo treatment sensitivity testing with positron emission tomography/computed tomography after one cycle of chemotherapy for Hodgkin lymphoma.

PURPOSE: Negative [(18)F]fluorodeoxyglucose (FDG) -positron emission tomography (PET)/computed tomography (CT) after two cycles of chemotherapy indicates a favorable prognosis in Hodgkin lymphoma (HL). We hypothesized that the negative predictive value would be even higher in patients responding rapidly enough to be PET negative after one cycle. This prospective study aimed to assess the prognostic value of PET after one cycle of chemotherapy in HL and to assess the dynamics of FDG uptake after one cycle (PET1) and after two cycles (PET2). PATIENTS AND METHODS: All PET scans were read by two blinded, independent reviewers in different countries, according to the Deauville five-point scale. The main end point was progression-free survival (PFS) after 2 years. RESULTS: A total of 126 patients were included, and all had PET1; 89 patients had both PET1 and PET2. The prognostic value of PET1 was statistically significant with respect to both PFS and overall survival. Two-year PFS for PET1-negative and PET1-positive patients was 94.1% and 40.8%, respectively. Among those with both PET1 and PET2, 2-year PFS was 98.3% and 38.5% for PET1-negative and PET1-positive patients and 90.2% and 23.1% for PET2-negative and PET2-positive patients, respectively. No PET1-negative patient was PET2 positive. CONCLUSION: PET after one cycle of chemotherapy is highly prognostic in HL. No other prognostic tool identifies a group of patients with HL with a more favorable outcome than those patients with a negative PET1. In the absence of precise pretherapeutic predictive markers, PET1 is the best method for response-adapted strategies designed to select patients for less intensive treatment.

Authors
Hutchings, M; Kostakoglu, L; Zaucha, JM; Malkowski, B; Biggi, A; Danielewicz, I; Loft, A; Specht, L; Lamonica, D; Czuczman, MS; Nanni, C; Zinzani, PL; Diehl, L; Stern, R; Coleman, M
MLA Citation
Hutchings, M, Kostakoglu, L, Zaucha, JM, Malkowski, B, Biggi, A, Danielewicz, I, Loft, A, Specht, L, Lamonica, D, Czuczman, MS, Nanni, C, Zinzani, PL, Diehl, L, Stern, R, and Coleman, M. "In vivo treatment sensitivity testing with positron emission tomography/computed tomography after one cycle of chemotherapy for Hodgkin lymphoma." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 32.25 (September 2014): 2705-2711.
PMID
25071108
Source
epmc
Published In
Journal of Clinical Oncology
Volume
32
Issue
25
Publish Date
2014
Start Page
2705
End Page
2711
DOI
10.1200/jco.2013.53.2838

Phase II open label study of the oral vascular endothelial growth factor-receptor inhibitor PTK787/ZK222584 (vatalanib) in adult patients with refractory or relapsed diffuse large B-cell lymphoma.

PTK787/ZK222584 (vatalanib), an orally active inhibitor of vascular endothelial growth factor receptors (VEGFRs), was evaluated in this phase II study of 20 patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Patients received once-daily PTK787/ZK222584 at a target dose of 1250 mg. Eighteen patients were evaluable for response: one patient had a complete response (CR), six patients had stable disease but subsequently progressed, 10 patients had progressive disease by three cycles and one subject withdrew before response evaluation. The patient who attained a CR underwent autologous stem cell transplant and remains disease-free 76 months after study completion. There were no grade 4 toxicities. Grade 3 thrombocytopenia occurred in 20% and grade 3 hypertension occurred in 10%. There were no episodes of grade 3 proteinuria. In conclusion, PTK787/ZK222584 was well tolerated in a heavily pretreated population of patients with DLBCL, although its therapeutic potential as a single agent in DLBCL appears limited.

Authors
Brander, D; Rizzieri, D; Gockerman, J; Diehl, L; Shea, TC; Decastro, C; Moore, JO; Beaven, A
MLA Citation
Brander, D, Rizzieri, D, Gockerman, J, Diehl, L, Shea, TC, Decastro, C, Moore, JO, and Beaven, A. "Phase II open label study of the oral vascular endothelial growth factor-receptor inhibitor PTK787/ZK222584 (vatalanib) in adult patients with refractory or relapsed diffuse large B-cell lymphoma." Leuk Lymphoma 54.12 (December 2013): 2627-2630.
PMID
23488610
Source
pubmed
Published In
Leukemia & Lymphoma (Informa)
Volume
54
Issue
12
Publish Date
2013
Start Page
2627
End Page
2630
DOI
10.3109/10428194.2013.784969

A Phase I study of arsenic trioxide (Trisenox), ascorbic acid, and bortezomib (Velcade) combination therapy in patients with relapsed/refractory multiple myeloma.

PURPOSE: This Phase I study assessed the feasibility of concomitant arsenic trioxide (ATO), ascorbic acid (AA), and bortezomib (Velcade™) (AAV) for patients with relapsed/refractory multiple myeloma. EXPERIMENTAL DESIGN: ATO (0.25 mg/kg) and AA (1 g) were given with an escalating dose of bortezomib (1 mg/m(2) or 1.3 mg/m(2) IV bolus on days 1 and 8 of a 21-day cycle). RESULTS: Ten patients (median age 62 years), with a median of 3 prior regimens, were enrolled. Four (40%) patients achieved clinical benefit, with one patient achieving a durable partial response. No formal DLTs were encountered. CONCLUSION: AAV combination was feasible and demonstrated some benefits in this heavily pretreated population.

Authors
Held, LA; Rizzieri, D; Long, GD; Gockerman, JP; Diehl, LF; de Castro, CM; Moore, JO; Horwitz, ME; Chao, NJ; Gasparetto, C
MLA Citation
Held, LA, Rizzieri, D, Long, GD, Gockerman, JP, Diehl, LF, de Castro, CM, Moore, JO, Horwitz, ME, Chao, NJ, and Gasparetto, C. "A Phase I study of arsenic trioxide (Trisenox), ascorbic acid, and bortezomib (Velcade) combination therapy in patients with relapsed/refractory multiple myeloma." Cancer Invest 31.3 (March 2013): 172-176.
PMID
23406188
Source
pubmed
Published In
Cancer Investigation (Informa)
Volume
31
Issue
3
Publish Date
2013
Start Page
172
End Page
176
DOI
10.3109/07357907.2012.756109

Re-induction therapy decisions based on day 14 bone marrow biopsy in acute myeloid leukemia.

PURPOSE: The decision to re-induce patients with acute myeloid leukemia (AML) based on results of the day 14 bone marrow (BM) biopsy is variable and lacks evidence based data. The aim of our review was to evaluate the accuracy of a day 14 BM biopsy in determining the need for re-induction chemotherapy. METHODS: Seventy-four patients with newly diagnosed de novo AML treated with induction chemotherapy were retrospectively reviewed for the purpose of evaluating treatment decisions and outcomes based on their day 14 BM biopsy. Response to therapy in this analysis was based on morphology alone. RESULTS: Of the 74 patients undergoing standard induction, 45 patients (61%) had no evidence of leukemia on their day 14 BM biopsy. Eighteen patients (24%) had definitive residual disease (RD), and 11 patient's (15%) were classified as indeterminate response (IR). Fifteen patients with RD and one with IR underwent re-induction chemotherapy. However, thirteen patients (3 RD and 10 IR) were observed until count recovery without any re-induction therapy. Eleven of these 13 patients who were observed eventually attained a morphologic complete remission (CR), including two patients with RD. CONCLUSIONS: A day 14 BM biopsy may have suboptimal sensitivity for the detection of residual leukemia. Some patients with an IR on day 14 may not require re-induction chemotherapy, but instead, may benefit from careful observation until count recovery to avoid the mortality and morbidity associated with re-induction chemotherapy.

Authors
Morris, TA; DeCastro, CM; Diehl, LF; Gockerman, JP; Lagoo, AS; Li, Z; Moore, JO; Rizzieri, DA; Rao, AV
MLA Citation
Morris, TA, DeCastro, CM, Diehl, LF, Gockerman, JP, Lagoo, AS, Li, Z, Moore, JO, Rizzieri, DA, and Rao, AV. "Re-induction therapy decisions based on day 14 bone marrow biopsy in acute myeloid leukemia." Leuk Res 37.1 (January 2013): 28-31.
PMID
23046833
Source
pubmed
Published In
Leukemia Research: clinical and laboratory studies
Volume
37
Issue
1
Publish Date
2013
Start Page
28
End Page
31
DOI
10.1016/j.leukres.2012.09.016

Chronic lymphocytic leukemia and regulatory B cells share IL-10 competence and immunosuppressive function.

Chronic lymphocytic leukemia (CLL) can be immunosuppressive in humans and mice, and CLL cells share multiple phenotypic markers with regulatory B cells that are competent to produce interleukin (IL)-10 (B10 cells). To identify functional links between CLL cells and regulatory B10 cells, the phenotypes and abilities of leukemia cells from 93 patients with overt CLL to express IL-10 were assessed. CD5(+) CLL cells purified from 90% of the patients were IL-10-competent and secreted IL-10 following appropriate ex vivo stimulation. Serum IL-10 levels were also significantly elevated in CLL patients. IL-10-competent cell frequencies were higher among CLLs with IgV(H) mutations, and correlated positively with TCL1 expression. In the TCL1-transgenic (TCL1-Tg) mouse model of CLL, IL-10-competent B cells with the cell surface phenotype of B10 cells expanded significantly with age, preceding the development of overt, CLL-like leukemia. Malignant CLL cells in TCL1-Tg mice also shared immunoregulatory functions with mouse and human B10 cells. Serum IL-10 levels varied in TCL1-Tg mice, but in vivo low-dose lipopolysaccharide treatment induced IL-10 expression in CLL cells and high levels of serum IL-10. Thus, malignant IL-10-competent CLL cells exhibit regulatory functions comparable to normal B10 cells that may contribute to the immunosuppression observed in patients and TCL1-Tg mice.

Authors
DiLillo, DJ; Weinberg, JB; Yoshizaki, A; Horikawa, M; Bryant, JM; Iwata, Y; Matsushita, T; Matta, KM; Chen, Y; Venturi, GM; Russo, G; Gockerman, JP; Moore, JO; Diehl, LF; Volkheimer, AD; Friedman, DR; Lanasa, MC; Hall, RP; Tedder, TF
MLA Citation
DiLillo, DJ, Weinberg, JB, Yoshizaki, A, Horikawa, M, Bryant, JM, Iwata, Y, Matsushita, T, Matta, KM, Chen, Y, Venturi, GM, Russo, G, Gockerman, JP, Moore, JO, Diehl, LF, Volkheimer, AD, Friedman, DR, Lanasa, MC, Hall, RP, and Tedder, TF. "Chronic lymphocytic leukemia and regulatory B cells share IL-10 competence and immunosuppressive function." Leukemia 27.1 (January 2013): 170-182.
PMID
22713648
Source
pubmed
Published In
Leukemia
Volume
27
Issue
1
Publish Date
2013
Start Page
170
End Page
182
DOI
10.1038/leu.2012.165

Chronic lymphocytic leukemia and regulatory B cells share IL-10 competence and immunosuppressive function

Chronic lymphocytic leukemia (CLL) can be immunosuppressive in humans and mice, and CLL cells share multiple phenotypic markers with regulatory B cells that are competent to produce interleukin (IL)-10 (B10 cells). To identify functional links between CLL cells and regulatory B10 cells, the phenotypes and abilities of leukemia cells from 93 patients with overt CLL to express IL-10 were assessed. CD5 + CLL cells purified from 90% of the patients were IL-10-competent and secreted IL-10 following appropriate ex vivo stimulation. Serum IL-10 levels were also significantly elevated in CLL patients. IL-10-competent cell frequencies were higher among CLLs with IgV H mutations, and correlated positively with TCL1 expression. In the TCL1-transgenic (TCL1-Tg) mouse model of CLL, IL-10-competent B cells with the cell surface phenotype of B10 cells expanded significantly with age, preceding the development of overt, CLL-like leukemia. Malignant CLL cells in TCL1-Tg mice also shared immunoregulatory functions with mouse and human B10 cells. Serum IL-10 levels varied in TCL1-Tg mice, but in vivo low-dose lipopolysaccharide treatment induced IL-10 expression in CLL cells and high levels of serum IL-10. Thus, malignant IL-10-competent CLL cells exhibit regulatory functions comparable to normal B10 cells that may contribute to the immunosuppression observed in patients and TCL1-Tg mice. © 2013 Macmillan Publishers Limited All rights reserved.

Authors
Dilillo, DJ; Weinberg, JB; Yoshizaki, A; Horikawa, M; Bryant, JM; Iwata, Y; Matsushita, T; Matta, KM; Chen, Y; Venturi, GM; Russo, G; Gockerman, JP; Moore, JO; Diehl, LF; Volkheimer, AD; Friedman, DR; Lanasa, MC; Hall, RP; Tedder, TF
MLA Citation
Dilillo, DJ, Weinberg, JB, Yoshizaki, A, Horikawa, M, Bryant, JM, Iwata, Y, Matsushita, T, Matta, KM, Chen, Y, Venturi, GM, Russo, G, Gockerman, JP, Moore, JO, Diehl, LF, Volkheimer, AD, Friedman, DR, Lanasa, MC, Hall, RP, and Tedder, TF. "Chronic lymphocytic leukemia and regulatory B cells share IL-10 competence and immunosuppressive function." Leukemia 27.1 (2013): 170-182.
Source
scival
Published In
Leukemia
Volume
27
Issue
1
Publish Date
2013
Start Page
170
End Page
182
DOI
10.1038/leu.2012.165

Combined-modality therapy for early-stage Hodgkin lymphoma: maintaining high cure rates while minimizing risks.

Multiple randomized studies have demonstrated that chemotherapy, most commonly ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, dacarbazine), followed by consolidation radiation therapy is the most effective treatment program for early-stage Hodgkin lymphoma. With a combined-modality approach, the great majority of patients are cured of their disease. It is also apparent that both chemotherapy and radiation therapy can increase the risk of complications in the decades following treatment, with second cancers and cardiac disease being the most common. Most studies,evaluating such risks primarily include patients treated in decades past with what are now considered outdated approaches, including high-dose, wide-field radiation therapy. The treatment of Hodgkin lymphoma has evolved significantly, particularly in regard to radiation therapy. In combination with chemotherapy, much lower doses and smaller fields are employed, with success equivalent to that achieved using older methods. Many studies have shown a significant decline in both the rates of second cancers and the risk of cardiac disease with low-dose radiation confined to the original extent of disease. In favorable patients, as few as 2 cycles of ABVD have been shown to be effective. The current combined-modality approach seeks to maintain high cure rates but minimize risks by optimizing both chemotherapy and radiation therapy

Authors
Kelsey, CR; Beaven, AW; Diehl, LF; Prosnitz, LR
MLA Citation
Kelsey, CR, Beaven, AW, Diehl, LF, and Prosnitz, LR. "Combined-modality therapy for early-stage Hodgkin lymphoma: maintaining high cure rates while minimizing risks." Oncology (Williston Park) 26.12 (December 2012): 1182-1193. (Review)
PMID
23413599
Source
pubmed
Published In
Oncology
Volume
26
Issue
12
Publish Date
2012
Start Page
1182
End Page
1193

Impact of consolidation radiation therapy in stage III-IV diffuse large B-cell lymphoma with negative post-chemotherapy radiologic imaging.

PURPOSE: While consolidation radiation therapy (i.e., RT administered after chemotherapy) is routine treatment for patients with early-stage diffuse large B-cell lymphoma (DLBCL), the role of consolidation RT in stage III-IV DLBCL is controversial. METHODS AND MATERIALS: Cases of patients with stage III-IV DLBCL treated from 1991 to 2009 at Duke University, who achieved a complete response to chemotherapy were reviewed. Clinical outcomes were calculated using the Kaplan-Meier method and were compared between patients who did and did not receive RT, using the log-rank test. A multivariate analysis was performed using Cox proportional hazards model. RESULTS: Seventy-nine patients were identified. Chemotherapy (median, 6 cycles) consisted of anti-CD20 antibody rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; 65%); cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP; 22%); or other (13%). Post-chemotherapy imaging consisted of positron emission tomography (PET)/computed tomography (CT) (73%); gallium with CT (14%); or CT only (13%). Consolidation RT (median, 25 Gy) was given to involved sites of disease in 38 (48%) patients. Receipt of consolidation RT was associated with improved in-field control (92% vs. 69%, respectively, p = 0.028) and event-free survival (85% vs. 65%, respectively, p = 0.014) but no difference in overall survival (85% vs. 78%, respectively, p = 0.15) when compared to patients who did not receive consolidation RT. On multivariate analysis, no RT was predictive of increased risk of in-field failure (hazard ratio [HR], 8.01, p = 0.014) and worse event-free survival (HR, 4.3, p = 0.014). CONCLUSIONS: Patients with stage III-IV DLBCL who achieve negative post-chemotherapy imaging have improved in-field control and event-free survival with low-dose consolidation RT.

Authors
Dorth, JA; Prosnitz, LR; Broadwater, G; Diehl, LF; Beaven, AW; Coleman, RE; Kelsey, CR
MLA Citation
Dorth, JA, Prosnitz, LR, Broadwater, G, Diehl, LF, Beaven, AW, Coleman, RE, and Kelsey, CR. "Impact of consolidation radiation therapy in stage III-IV diffuse large B-cell lymphoma with negative post-chemotherapy radiologic imaging." Int J Radiat Oncol Biol Phys 84.3 (November 1, 2012): 762-767.
PMID
22420972
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
84
Issue
3
Publish Date
2012
Start Page
762
End Page
767
DOI
10.1016/j.ijrobp.2011.12.067

Phase II study of cenersen, an antisense inhibitor of p53, in combination with fludarabine, cyclophosphamide and rituximab for high-risk chronic lymphocytic leukemia.

Patients with chronic lymphocytic leukemia (CLL) with deletion or mutation of TP53 have exceedingly poor clinical outcomes. Cenersen, an oligonucleotide targeting TP53, has been shown to abrogate the activity of TP53 gain-of-function mutants and to increase sensitivity of lymphoma cells to cytotoxic chemotherapy in vitro. We combined cenersen with fludarabine, cyclophosphamide and rituximab (FCR) as treatment for patients with high-risk CLL. The purpose of this phase II study was to determine the overall response rate, response duration and toxicity of cenersen administered in combination with FCR. Twenty patients with relapsed or high-risk CLL were evaluated. Nineteen patients were previously treated. The complete response rate was 18%; the overall response rate was 53%. Median progression-free and overall survival was 5.3 and 10.6 months, respectively. The most common serious adverse events were neutropenia and thrombocytopenia. In this single arm phase II study, cenersen combined with FCR yielded clinical responses with acceptable toxicity in patients with high-risk CLL.

Authors
Lanasa, MC; Davis, PH; Datto, M; Li, Z; Gockerman, JP; Moore, JO; DeCastro, CM; Friedman, DR; Diehl, LF; Rehder, C; Cook, H; Daugherty, FJ; Matta, KMB; Weinberg, JB; Rizzieri, D
MLA Citation
Lanasa, MC, Davis, PH, Datto, M, Li, Z, Gockerman, JP, Moore, JO, DeCastro, CM, Friedman, DR, Diehl, LF, Rehder, C, Cook, H, Daugherty, FJ, Matta, KMB, Weinberg, JB, and Rizzieri, D. "Phase II study of cenersen, an antisense inhibitor of p53, in combination with fludarabine, cyclophosphamide and rituximab for high-risk chronic lymphocytic leukemia." Leuk Lymphoma 53.2 (February 2012): 218-224.
PMID
21827374
Source
pubmed
Published In
Leukemia & Lymphoma (Informa)
Volume
53
Issue
2
Publish Date
2012
Start Page
218
End Page
224
DOI
10.3109/10428194.2011.610012

Phase I study of dose dense induction and consolidation with gemtuzumab ozogamicin and high dose cytarabine in older adults with AML

Objective: Older adults with acute myeloid leukemia (AML) tend to have worse complete remission (CR) rates and overall survival compared to their younger counterparts. At least one reason for this is increased expression of the multidrug resistance gene (MDR1). Dose dense, high intensity chemotherapy may overcome the MDR1 effect, possibly when combined with anti-CD33 monoclonal antibody gemtuzumab ozogamicin (GO,Mylotarg™), which has been studied in older adults with relapsed AML. This phase I study was aimed at establishing safety by defining a maximum tolerated dose (MTD) by treating older AML patients with two cycles of dose-dense therapy with high dose cytarabine (HiDAC) combined with targeted therapy using GO. Materials and methods: Nine patients ≥60years with newly diagnosed, untreated CD33+ AML with adequate renal and hepatic function, and ECOG PS 0-2 were eligible. HiDAC was administered at two dose levels: 3000mg/m 2 every 12h for 6 doses (cohort 1), or 9 doses (cohort 2). GO was administered at 6mg/m 2 on days 1 and 8. Results: The MTD was HiDAC 3000mg/m 2 for six doses along with GO 6mg/m 2. All patients had grades 3-4 pancytopenia, and two patients developed reversible grade 2 neurotoxicity. There were no cases of veno-occlusive disease. Seven of nine patients had a complete response (CR or CRp). Conclusions: There was no difference in relapse-free survival in our patients when compared to historical data. However, despite high toxicity, two of nine patients treated in this dose-dense fashion remained in CR for > 60 months. © 2012 Elsevier Inc.

Authors
Rao, AV; Rizzieri, DA; DeCastro, CM; Diehl, LF; Lagoo, AS; Moore, JO; Gockerman, JP
MLA Citation
Rao, AV, Rizzieri, DA, DeCastro, CM, Diehl, LF, Lagoo, AS, Moore, JO, and Gockerman, JP. "Phase I study of dose dense induction and consolidation with gemtuzumab ozogamicin and high dose cytarabine in older adults with AML." Journal of Geriatric Oncology 3.3 (2012): 220-227.
Source
scival
Published In
Journal of Geriatric Oncology
Volume
3
Issue
3
Publish Date
2012
Start Page
220
End Page
227
DOI
10.1016/j.jgo.2012.02.002

Combined-modality therapy for early-stage Hodgkin lymphoma: Maintaining high cure rates while minimizing risks

Multiple randomized studies have demonstrated that chemotherapy, most commonly ABVD (doxorubicin [Adriamycin], bleomycin(Drug information on bleomycin), vinblastine(Drug information on vinblastine), dacarbazine(Drug information on dacarbazine)), followed by consolidation radiation therapy is the most effective treatment program for early-stage Hodgkin lymphoma. With a combined-modality approach, the great majority of patients are cured of their disease. It is also apparent that both chemotherapy and radiation therapy can increase the risk of complications in the decades following treatment, with second cancers and cardiac disease being the most common. Most studies evaluating such risks primarily include patients treated in decades past with what are now considered outdated approaches, including high-dose, wide-field radiation therapy. The treatment of Hodgkin lymphoma has evolved significantly, particularly in regard to radiation therapy. In combination with chemotherapy, much lower doses and smaller fields are employed, with success equivalent to that achieved using older methods. Many studies have shown a significant decline in both the rates of second cancers and the risk of cardiac disease with low-dose radiation confined to the original extent of disease. In favorable patients, as few as 2 cycles of ABVD have been shown to be effective. The current combined-modality approach seeks to maintain high cure rates but minimize risks by optimizing both chemotherapy and radiation therapy.

Authors
Kelsey, CR; Beaven, AW; Diehl, LF; Prosnitz, LR
MLA Citation
Kelsey, CR, Beaven, AW, Diehl, LF, and Prosnitz, LR. "Combined-modality therapy for early-stage Hodgkin lymphoma: Maintaining high cure rates while minimizing risks." ONCOLOGY (United States) 26.12 (2012).
Source
scival
Published In
Oncology
Volume
26
Issue
12
Publish Date
2012

SET oncoprotein overexpression in B-cell chronic lymphocytic leukemia and non-Hodgkin lymphoma: a predictor of aggressive disease and a new treatment target.

B-cell chronic lymphocytic leukemia (CLL), an incurable leukemia, is characterized by defective apoptosis. We found that the SET oncoprotein, a potent inhibitor of the protein phosphatase 2A (PP2A) tumor suppressor, is overexpressed in primary CLL cells and B-cell non-Hodgkin lymphoma (NHL) cell line cells. In CLL, increased levels of SET correlated significantly with disease severity (shorter time to treatment and overall survival). We developed SET antagonist peptides that bound SET, increased cellular PP2A activity, decreased Mcl-1 expression, and displayed selective cytotoxicity for CLL and NHL cells in vitro. In addition, shRNA for SET was cytotoxic for NHL cells in vitro. The SET antagonist peptide COG449 inhibited growth of NHL tumor xenografts in mice. These data demonstrate that SET is a new treatment target in B-cell malignancies and that SET antagonists represent novel agents for treatment of CLL and NHL.

Authors
Christensen, DJ; Chen, Y; Oddo, J; Matta, KM; Neil, J; Davis, ED; Volkheimer, AD; Lanasa, MC; Friedman, DR; Goodman, BK; Gockerman, JP; Diehl, LF; de Castro, CM; Moore, JO; Vitek, MP; Weinberg, JB
MLA Citation
Christensen, DJ, Chen, Y, Oddo, J, Matta, KM, Neil, J, Davis, ED, Volkheimer, AD, Lanasa, MC, Friedman, DR, Goodman, BK, Gockerman, JP, Diehl, LF, de Castro, CM, Moore, JO, Vitek, MP, and Weinberg, JB. "SET oncoprotein overexpression in B-cell chronic lymphocytic leukemia and non-Hodgkin lymphoma: a predictor of aggressive disease and a new treatment target." Blood 118.15 (October 13, 2011): 4150-4158.
PMID
21844565
Source
pubmed
Published In
Blood
Volume
118
Issue
15
Publish Date
2011
Start Page
4150
End Page
4158
DOI
10.1182/blood-2011-04-351072

The impact of radiation therapy in patients with diffuse large B-cell lymphoma with positive post-chemotherapy FDG-PET or gallium-67 scans.

BACKGROUND: 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography (PET) and gallium-67 citrate (gallium) response after chemotherapy are powerful prognostic factors in diffuse large B-cell lymphoma (DLBCL). However, clinical outcomes when consolidation radiation therapy (RT) is administered are less defined. PATIENTS AND METHODS: We reviewed 99 patients diagnosed with DLBCL from 1996 to 2007 at Duke University who had a post-chemotherapy response assessment with either PET or gallium and who subsequently received consolidation RT. Clinical outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: Median follow-up was 4.4 years. Stage distribution was I-II in 70% and III-IV in 30%. Chemotherapy was R-CHOP or CHOP in 88%. Median RT dose was 30 Gy. Post-chemotherapy PET (n = 79) or gallium (n = 20) was positive in 21 of 99 patients and negative in 78 of 99 patients. Five-year in-field control was 95% with a negative PET/gallium scan versus 71% with a positive scan (P < 0.01). Five-year event-free survival (EFS; 83% versus 65%, P = 0.04) and overall survival (89% versus 73%, P = 0.04) were also significantly better when the post-chemotherapy PET/gallium was negative. CONCLUSIONS: A positive PET/gallium scan after chemotherapy is associated with an increased risk of local failure and death. Consolidation RT, however, still results in long-term EFS in 65% of patients.

Authors
Dorth, JA; Chino, JP; Prosnitz, LR; Diehl, LF; Beaven, AW; Coleman, RE; Kelsey, CR
MLA Citation
Dorth, JA, Chino, JP, Prosnitz, LR, Diehl, LF, Beaven, AW, Coleman, RE, and Kelsey, CR. "The impact of radiation therapy in patients with diffuse large B-cell lymphoma with positive post-chemotherapy FDG-PET or gallium-67 scans." Ann Oncol 22.2 (February 2011): 405-410.
PMID
20675560
Source
pubmed
Published In
Annals of Oncology
Volume
22
Issue
2
Publish Date
2011
Start Page
405
End Page
410
DOI
10.1093/annonc/mdq389

A Phase II trial of gemcitabine and mitoxantrone for patients with acute myeloid leukemia in first relapse.

INTRODUCTION: We evaluated the complete remission (CR) rate in patients with acute myeloid leukemia (AML) in first relapse treated with fixed-dose-rate gemcitabine and mitoxantrone. In addition, we measured multidrug resistance (MDR) proteins on pretreatment bone marrows and correlated expression with outcome. PATIENTS AND METHODS: The study was performed in a 2-stage design. Pretreatment bone marrows were assayed for the MDR proteins (LRP, MDR1, MRP1, SLC28-29A1/A2, ABCC4/C5, and GSTP1) by immunohistochemistry and reverse-transcriptase polymerase chain reaction (RT-PCR). RESULTS: Only 5 of the first 24 patients (21%) achieved CR; therefore, the study was terminated. Eleven patients (46%) had poor-risk cytogenetics and the median duration of first CR was 7.3 months. Patients had significant expression of the various MDR genes, with 70% of patients expressing moderate to high levels of GSTP1 by immunohistochemistry. Higher sum total of ABCC4 and SLC29A2 expression measured by RT-PCR was associated with not achieving CR (20.6 vs. 12.1; P = .006). In addition, there was a trend for higher expression of the sum total of the 10 MDR genes (measured by RT-PCR) and not achieving CR (P = .06). CONCLUSION: The CR rate in this study was comparable to other regimens used in poor-risk patients. Of interest, ABCC4 and SLC29A2 expression were predictive of achieving CR. The high expression of GSTP1 suggests that this may be a therapeutic target for relapsed AML. Finally, the rapidity and ease of using RT-PCR to quantify MDR in this study may have clinical utility in future trials.

Authors
Advani, AS; Shadman, M; Ali-Osman, F; Barker, A; Rybicki, L; Kalaycio, M; Sekeres, MA; de Castro, CM; Diehl, LF; Moore, JO; Beaven, A; Copelan, E; Sobecks, R; Talea, P; Rizzieri, DA
MLA Citation
Advani, AS, Shadman, M, Ali-Osman, F, Barker, A, Rybicki, L, Kalaycio, M, Sekeres, MA, de Castro, CM, Diehl, LF, Moore, JO, Beaven, A, Copelan, E, Sobecks, R, Talea, P, and Rizzieri, DA. "A Phase II trial of gemcitabine and mitoxantrone for patients with acute myeloid leukemia in first relapse." Clin Lymphoma Myeloma Leuk 10.6 (December 2010): 473-476.
PMID
21156465
Source
pubmed
Published In
Clinical Lymphoma, Myeloma and Leukemia
Volume
10
Issue
6
Publish Date
2010
Start Page
473
End Page
476
DOI
10.3816/CLML.2010.n.082

Radiation therapy in the management of diffuse large B-cell lymphoma: still relevant?

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in the United States. Historically, radiation therapy (RT) was the primary treatment for patients with localized disease. Several randomized trials have demonstrated that the addition of systemic therapy improves outcomes. Additional randomized trials have shown that the combination of RT and systemic therapy is superior to systemic therapy alone. The role of RT in advanced-stage DLBCL has not been firmly established, but some prospective phase III trials, as well as retrospective studies, suggest a benefit for advanced disease also. For patients with relapsed or primary refractory disease, autologous stem cell transplantation is the treatment of choice. Here too, consolidation RT appears to improve outcomes compared with autologous stem cell transplant alone. Finally, for patients with advanced DLBCL who are no longer responsive to systemic therapy, RT may provide rapid and durable palliation of local lymphoma-related symptoms.

Authors
Kelsey, CR; Beaven, AW; Diehl, LF; Prosnitz, LR
MLA Citation
Kelsey, CR, Beaven, AW, Diehl, LF, and Prosnitz, LR. "Radiation therapy in the management of diffuse large B-cell lymphoma: still relevant?." Oncology (Williston Park) 24.13 (November 30, 2010): 1204-1212.
PMID
21192559
Source
pubmed
Published In
Oncology
Volume
24
Issue
13
Publish Date
2010
Start Page
1204
End Page
1212

LMP-420: a novel purine nucleoside analog with potent cytotoxic effects for CLL cells and minimal toxicity for normal hematopoietic cells.

B-cell chronic lymphocytic leukemia (CLL) is characterized by slow accumulation of malignant cells, which are supported in the microenvironment by cell-cell interactions and soluble cytokines such as tumor necrosis factor (TNF). We evaluated the effect of the small molecule TNF inhibitor LMP-420 on primary CLL cells. The mean concentration of LMP-420 required to induce 50% cytotoxicity (ED50) at 72 h was 245 n. LMP-420-induced time- and dose-dependent apoptosis, as shown by annexin V staining, caspase activation and DNA fragmentation. These changes were associated with decreased expression of anti-apoptotic proteins Mcl-1, Bcl-xL and Bcl-2. CLL cells from patients with poor prognostic indicators showed LMP-420 sensitivity equal to that for cells from patients with favorable characteristics. In addition, LMP-420 potentiated the cytotoxic effect of fludarabine and inhibited in vitro proliferation of stimulated CLL cells. Gene expression profiling indicated that the mechanism of action of LMP-420 may involve suppression of nuclear factor-kappaB and immune response pathways in CLL cells. LMP-420 had minimal effects on normal peripheral blood mononuclear cell, B- and T-cell function, and hematopoietic colony formation. Our data suggest that LMP-420 may be a useful treatment for CLL with negligible hematologic toxicities.

Authors
Mowery, YM; Weinberg, JB; Kennedy, MN; Bond, KM; Moore, JO; Lanasa, MC; Gockerman, JP; Diehl, LF; Pizzo, SV; Cianciolo, GJ; Friedman, DR
MLA Citation
Mowery, YM, Weinberg, JB, Kennedy, MN, Bond, KM, Moore, JO, Lanasa, MC, Gockerman, JP, Diehl, LF, Pizzo, SV, Cianciolo, GJ, and Friedman, DR. "LMP-420: a novel purine nucleoside analog with potent cytotoxic effects for CLL cells and minimal toxicity for normal hematopoietic cells." Leukemia 24.9 (September 2010): 1580-1587.
PMID
20613784
Source
pubmed
Published In
Leukemia
Volume
24
Issue
9
Publish Date
2010
Start Page
1580
End Page
1587
DOI
10.1038/leu.2010.150

Overcoming drug resistance in mantle cell lymphoma using a combination of dose-dense and intense therapy.

We present a study of the prevalence of genetic polymorphisms and expression of genes encoding the drug-resistance proteins glutathione S-transferases (GSTs) in order to gain insights into the pattern of failure evident in mantle cell lymphoma. We note a high preponderance of genetic alterations conferring resistance to standard chemotherapy in this illness. Concurrent with this investigation, we present a series of patients who were provided dose-dense and intense chemotherapy to circumvent these drug-resistance mechanisms. High responses were noted, though durable remissions were few, indicating non-traditional chemotherapy options are important to investigate in this illness.

Authors
Crout, CA; Koh, L-P; Gockerman, JP; Moore, JO; Decastro, C; Long, GD; Diehl, L; Gasparetto, C; Niedzwiecki, D; Edwards, J; Prosnitz, L; Horwitz, M; Chute, J; Morris, A; Davis, P; Beaven, A; Chao, NJ; Ali-Osman, F; Rizzieri, DA
MLA Citation
Crout, CA, Koh, L-P, Gockerman, JP, Moore, JO, Decastro, C, Long, GD, Diehl, L, Gasparetto, C, Niedzwiecki, D, Edwards, J, Prosnitz, L, Horwitz, M, Chute, J, Morris, A, Davis, P, Beaven, A, Chao, NJ, Ali-Osman, F, and Rizzieri, DA. "Overcoming drug resistance in mantle cell lymphoma using a combination of dose-dense and intense therapy." Cancer Invest 28.6 (July 2010): 654-660.
PMID
20521909
Source
pubmed
Published In
Cancer Investigation (Informa)
Volume
28
Issue
6
Publish Date
2010
Start Page
654
End Page
660
DOI
10.3109/07357901003631015

"Short course" bortezomib plus melphalan and prednisone as induction prior to transplant or as frontline therapy for nontransplant candidates in patients with previously untreated multiple myeloma.

The purpose of this study was to evaluate the efficacy and safety of short-course bortezomib, melphalan, prednisone (VMP) in previously untreated multiple myeloma as frontline therapy for transplant-ineligible patients and induction prior to autologous stem cell transplantation (ASCT). Patients received up to 6 28-day cycles of bortezomib 1.3 mg/m(2), days 1, 4, 8, and 11, plus melphalan 6 mg/m(2) and prednisone 60 mg/m(2), days 1-7. After 2-6 cycles, eligible and consenting patients could proceed to ASCT. Responses were assessed by International Uniform Response Criteria. The primary endpoint was complete response (CR) rate with VMP. Forty-five patients were enrolled. Among 44 evaluable patients, response rate was 95%, including 18% >or=CR (9% stringent CR), 27% very good partial responses (VGPR), and 50% partial responses (PR). Twenty patients proceeded to ASCT. Stem cell collection was successful in all; median yield was 5.6 x 10(6) CD34(+) cells/kg. Posttransplant response rates were 30% >or=CR (10% stringent CR), 65% VGPR, and 5% PR. After median follow-up of 14.0/14.6 months, median time to progression and progression-free survival were both 19.8/27.9 months in non-ASCT/ASCT patients. Seven patients have died; 1-year survival rates were 82%/95% in non-ASCT/ASCT patients. The most common grade 3/4 toxicities were thrombocytopenia (20%), neutropenia (28%), and infection (9%). Peripheral neuropathy grade 2-4 was the most common nonhematopoietic side effect occurring 17 patients (38%), although it was typically reversible, and only 5 patients (11%) discontinued therapy as a result of it. Short-course VMP is highly effective and generally well tolerated, both as initial treatment in non-ASCT patients and induction prior to ASCT. VMP did not negatively affect stem cell collection. Longer follow-up and prospective phase III trials are required to validate these initial observations.

Authors
Gasparetto, C; Gockerman, JP; Diehl, LF; de Castro, CM; Moore, JO; Long, GD; Horwitz, ME; Keogh, G; Chute, JP; Sullivan, KM; Neuwirth, R; Davis, PH; Sutton, LM; Anderson, RD; Chao, NJ; Rizzieri, D
MLA Citation
Gasparetto, C, Gockerman, JP, Diehl, LF, de Castro, CM, Moore, JO, Long, GD, Horwitz, ME, Keogh, G, Chute, JP, Sullivan, KM, Neuwirth, R, Davis, PH, Sutton, LM, Anderson, RD, Chao, NJ, and Rizzieri, D. ""Short course" bortezomib plus melphalan and prednisone as induction prior to transplant or as frontline therapy for nontransplant candidates in patients with previously untreated multiple myeloma." Biol Blood Marrow Transplant 16.1 (January 2010): 70-77.
PMID
19733251
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
16
Issue
1
Publish Date
2010
Start Page
70
End Page
77
DOI
10.1016/j.bbmt.2009.08.017

Radiation therapy in the management of diffuse large B-cell lymphoma: still relevant?

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in the United States. Historically, radiation therapy (RT) was the primary treatment for patients with localized disease. Several randomized trials have demonstrated that the addition of systemic therapy improves outcomes. Additional randomized trials have shown that the combination of RT and systemic therapy is superior to systemic therapy alone. The role of RT in advanced-stage DLBCL has not been firmly established, but some prospective phase III trials, as well as retrospective studies, suggest a benefit for advanced disease also. For patients with relapsed or primary refractory disease, autologous stem cell transplantation is the treatment of choice. Here too, consolidation RT appears to improve outcomes compared with autologous stem cell transplant alone. Finally, for patients with advanced DLBCL who are no longer responsive to systemic therapy, RT may provide rapid and durable palliation of local lymphoma-related symptoms.

Authors
Kelsey, CR; Beaven, AW; Diehl, LF; Prosnitz, LR
MLA Citation
Kelsey, CR, Beaven, AW, Diehl, LF, and Prosnitz, LR. "Radiation therapy in the management of diffuse large B-cell lymphoma: still relevant?." Oncology (Williston Park, N.Y.) 24.13 (2010): 1204-1212.
Source
scival
Published In
Oncology
Volume
24
Issue
13
Publish Date
2010
Start Page
1204
End Page
1212

Statin use and need for therapy in chronic lymphocytic leukemia

Authors
Friedman, DR; Magura, LA; Warren, HAC; Harrison, JD; Diehl, LF; Weinberg, JB
MLA Citation
Friedman, DR, Magura, LA, Warren, HAC, Harrison, JD, Diehl, LF, and Weinberg, JB. "Statin use and need for therapy in chronic lymphocytic leukemia." Leukemia and Lymphoma 51.12 (2010): 2295-2298.
PMID
20929315
Source
scival
Published In
Leukemia & Lymphoma (Informa)
Volume
51
Issue
12
Publish Date
2010
Start Page
2295
End Page
2298
DOI
10.3109/10428194.2010.520050

A genomic approach to improve prognosis and predict therapeutic response in chronic lymphocytic leukemia.

PURPOSE: Chronic lymphocytic leukemia (CLL) is a B-cell malignancy characterized by a variable clinical course. Several parameters have prognostic capabilities but are associated with altered response to therapy in only a small subset of patients. EXPERIMENTAL DESIGN: We used gene expression profiling methods to generate predictors of therapy response and prognosis. Genomic signatures that reflect progressive disease and responses to chemotherapy or chemoimmunotherapy were created using cancer cell lines and patient leukemia cell samples. We validated and applied these three signatures to independent clinical data from four cohorts, representing a total of 301 CLL patients. RESULTS: A genomic signature of prognosis created from patient leukemic cell gene expression data coupled with clinical parameters significantly differentiated patients with stable disease from those with progressive disease in the training data set. The progression signature was validated in two independent data sets, showing a capacity to accurately identify patients at risk for progressive disease. In addition, genomic signatures that predict response to chlorambucil or pentostatin, cyclophosphamide, and rituximab were generated and could accurately distinguish responding and nonresponding CLL patients. CONCLUSIONS: Thus, microarray analysis of CLL lymphocytes can be used to refine prognosis and predict response to different therapies. These results have implications for standard and investigational therapeutics in CLL patients.

Authors
Friedman, DR; Weinberg, JB; Barry, WT; Goodman, BK; Volkheimer, AD; Bond, KM; Chen, Y; Jiang, N; Moore, JO; Gockerman, JP; Diehl, LF; Decastro, CM; Potti, A; Nevins, JR
MLA Citation
Friedman, DR, Weinberg, JB, Barry, WT, Goodman, BK, Volkheimer, AD, Bond, KM, Chen, Y, Jiang, N, Moore, JO, Gockerman, JP, Diehl, LF, Decastro, CM, Potti, A, and Nevins, JR. "A genomic approach to improve prognosis and predict therapeutic response in chronic lymphocytic leukemia." Clin Cancer Res 15.22 (November 15, 2009): 6947-6955.
PMID
19861443
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
15
Issue
22
Publish Date
2009
Start Page
6947
End Page
6955
DOI
10.1158/1078-0432.CCR-09-1132

T cell large granular lymphocyte leukemia associated with rheumatoid arthritis and neutropenia.

T cell large granular lymphocyte leukemia (T-LGL) is a disease characterized by clonal expansion of cytotoxic T cells (CTLs). It generally follows an indolent course and is notable for an association with chronic inflammation, neutropenia and rheumatoid arthritis (RA). We present herein a case of a patient with rheumatoid arthritis (RA), neutropenia, large granular lymphocytosis, and an expanded clonal population of peripheral blood CD3(+)CD8(+)TCRalphabeta CTLs, consistent with the diagnosis of T-LGL. T-LGL is part of a spectrum of large granular lymphocytic (LGL) disorders, which includes the more common indolent variety of this disease (as illustrated by the case herein), an aggressive but rare form of this leukemia, natural killer (NK) cell LGL leukemia, Felty's syndrome (FS), and chronic large granular lymphocytosis. T-LGL appears to be a relatively rare disease, but the true prevalence is not known. FS occurs in less than 1% of patients with RA and is typically defined by the triad of destructive arthritis, neutropenia, and variable splenomegaly. A subset of patients with FS will demonstrate polyclonal expansion of LGLs, implying a relationship between proliferation of LGLs and the mechanisms of neutropenia. Thus, T-LGL leukemia and FS with LGL expansion in the setting of RA is classically distinguished by the clonality of the CTL population, with monoclonality in T-LGL and polyclonality in FS. Despite this difference, T-LGL and FS are often similar in their clinical and biological behavior. Both may respond to immunosuppressive therapy, and pursue a smoldering course typical of a chronic inflammatory disease.

Authors
Shah, A; Diehl, LF; St Clair, EW
MLA Citation
Shah, A, Diehl, LF, and St Clair, EW. "T cell large granular lymphocyte leukemia associated with rheumatoid arthritis and neutropenia." Clin Immunol 132.2 (August 2009): 145-152.
PMID
19394280
Source
pubmed
Published In
Clinical Immunology
Volume
132
Issue
2
Publish Date
2009
Start Page
145
End Page
152
DOI
10.1016/j.clim.2009.03.515

Outcomes of patients who undergo aggressive induction therapy for secondary acute myeloid leukemia.

BACKGROUND: Response and survival in 96 patients with secondary acute myeloid leukemia (sAML) who received aggressive induction chemotherapy was reviewed. METHODS: The median follow-up of survivors was 2.3 years. A total of 70 (73%) patients achieved a morphologic complete remission (CR) confirmed by absence of leukemic blasts by flow cytometry. RESULTS: For all 96 patients, the median event-free survival (EFS) was 8 months, and overall survival (OS) was 13.6 months (range, 1-119 months). Eight patients died shortly after induction therapy because of disease or side effects, and 13 are currently in continuous first remission. The median disease-free survival (DFS) for all 70 patients who achieved a morphologic CR was 9 months (range, 1-51 months), with a 64% chance of surviving 1 year. Patients with AML after previous chemotherapy or radiation therapy had a higher morphologic remission rate compared with those arising from myelodysplastic syndrome or myeloproliferative disease (82% vs 62%; P = .027). However, among the patients from the 2 groups who attained a morphologic remission, there was no difference in terms of CR rate (P = .94), DFS, EFS, or OS (P = .55, .83, and .71, respectively). This is a similar DFS to the group of 7 patients who went directly to ablative allogeneic transplant rather than having induction therapy first. In this population of patients who received aggressive chemotherapy, Charlson comorbidity index or a higher number of factors recognized as high risk in leukemia patients did not affect the chance of OS, DFS, and EFS, although having more recognized leukemia risk factors was related to a lower chance of surviving 1 year. However, it is important to note that those with higher comorbidity indexes were underrepresented in this aggressively treated cohort. CONCLUSIONS: The data from the current study demonstrate that many patients with sAML can tolerate aggressive induction therapy and attain remission, but duration of response and the chance of long-term survival remain poor.

Authors
Rizzieri, DA; O'Brien, JA; Broadwater, G; Decastro, CM; Dev, P; Diehl, L; Beaven, A; Lagoo, A; Gockerman, JP; Chao, NJ; Moore, JO
MLA Citation
Rizzieri, DA, O'Brien, JA, Broadwater, G, Decastro, CM, Dev, P, Diehl, L, Beaven, A, Lagoo, A, Gockerman, JP, Chao, NJ, and Moore, JO. "Outcomes of patients who undergo aggressive induction therapy for secondary acute myeloid leukemia." Cancer 115.13 (July 1, 2009): 2922-2929.
PMID
19452542
Source
pubmed
Published In
Cancer
Volume
115
Issue
13
Publish Date
2009
Start Page
2922
End Page
2929
DOI
10.1002/cncr.24379

P134 A phase II pilot study of sorafenib in patients with myelodysplastic syndromes

Authors
Castro, CD; Adams, D; Rizzieri, D; Moore, J; Gockerman, J; Diehl, L; Horwitz, M; Edmonds, E; Warzecho, J
MLA Citation
Castro, CD, Adams, D, Rizzieri, D, Moore, J, Gockerman, J, Diehl, L, Horwitz, M, Edmonds, E, and Warzecho, J. "P134 A phase II pilot study of sorafenib in patients with myelodysplastic syndromes." Leukemia Research 33.SUPPL. 1 (2009): S137-.
Source
scival
Published In
Leukemia Research
Volume
33
Issue
SUPPL. 1
Publish Date
2009
Start Page
S137
DOI
10.1016/S0145-2126(09)70215-2

P129 A pilot study of decitabine in combination with arsenic trioxide for patients with myelodysplastic syndromes

Authors
Castro, CD; Adams, D; Rizzieri, D; Moore, J; Gockerman, J; Diehl, L; Horwitz, M; Edmonds, E; Warzecho, J
MLA Citation
Castro, CD, Adams, D, Rizzieri, D, Moore, J, Gockerman, J, Diehl, L, Horwitz, M, Edmonds, E, and Warzecho, J. "P129 A pilot study of decitabine in combination with arsenic trioxide for patients with myelodysplastic syndromes." Leukemia Research 33.SUPPL. 1 (2009): S134-.
Source
scival
Published In
Leukemia Research
Volume
33
Issue
SUPPL. 1
Publish Date
2009
Start Page
S134
DOI
10.1016/S0145-2126(09)70210-3

Apolipoprotein E genotype as a determinant of survival in chronic lymphocytic leukemia.

Survival of chronic lymphocytic leukemia (CLL) cells requires sustained activation of the antiapoptotic PI-3-K/Akt pathway, and many therapies for CLL cause leukemia cell death by triggering apoptosis. Blood lipoprotein particles are either pro- or antiapoptotic. High-density lipoprotein particles are antiapoptotic through sphingosine-1-phosphate receptor 3-mediated activation of the PI-3-K/Akt pathway. Apolipoprotein E4 (apoE4)-very low density lipoproteins (VLDL) increase apoptosis, but the apoE2-VLDL and apoE3-VLDL isoforms do not. As increased B-cell apoptosis favors longer survival of CLL patients, we hypothesized that APOE4 genotype would beneficially influence the clinical course of CLL. We report here that women (but not men) with an APOE4 genotype had markedly longer survival than non-APOE4 patients. VLDL is metabolized to low-density lipoprotein through lipoprotein lipase. Higher levels of lipoprotein lipase mRNA in these CLL patients correlated with shorter survival. The beneficial effect of APOE4 in CLL survival is likely mediated through APOE4 allele-specific regulation of leukemia cell apoptosis. The APOE allele and genotype distribution in these CLL patients is the same as in unaffected control populations, suggesting that although APOE genotype influences CLL outcome and response to therapy, it does not alter susceptibility to developing this disease.

Authors
Weinberg, JB; Volkheimer, AD; Mihovilovic, M; Jiang, N; Chen, Y; Bond, K; Moore, JO; Gockerman, JP; Diehl, LF; de Castro, CM; Rizzieri, DA; Levesque, MC; Dekroon, R; Strittmatter, WJ
MLA Citation
Weinberg, JB, Volkheimer, AD, Mihovilovic, M, Jiang, N, Chen, Y, Bond, K, Moore, JO, Gockerman, JP, Diehl, LF, de Castro, CM, Rizzieri, DA, Levesque, MC, Dekroon, R, and Strittmatter, WJ. "Apolipoprotein E genotype as a determinant of survival in chronic lymphocytic leukemia." Leukemia 22.12 (December 2008): 2184-2192.
PMID
18784741
Source
pubmed
Published In
Leukemia
Volume
22
Issue
12
Publish Date
2008
Start Page
2184
End Page
2192
DOI
10.1038/leu.2008.241

Apolipoprotein E-Mimetic Therapeutic Peptides Mediate CLL Cell Cytotoxicity

Authors
Christensen, DJ; Bond, KM; Volkheimer, AD; Oddo, J; Chen, Y; Gockerrnan, JP; Moore, JO; Diehl, LF; de Castro, CM; Vitek, MP; Weinberg, B
MLA Citation
Christensen, DJ, Bond, KM, Volkheimer, AD, Oddo, J, Chen, Y, Gockerrnan, JP, Moore, JO, Diehl, LF, de Castro, CM, Vitek, MP, and Weinberg, B. "Apolipoprotein E-Mimetic Therapeutic Peptides Mediate CLL Cell Cytotoxicity." BLOOD 112.11 (November 16, 2008): 140-140.
Source
wos-lite
Published In
Blood
Volume
112
Issue
11
Publish Date
2008
Start Page
140
End Page
140

Bortezomib Plus Melphalan and Prednisone as Induction Prior to Transplant or as Frontline Therapy for Non-Transplant Candidates in Patients with Previously Untreated Multiple Myeloma

Authors
Gasparet, C; Gockerman, JP; Diehl, LF; III, DCC; Moore, J; Long, GD; Horwitz, M; Chute, J; Sullivan, KM; Netuwirth, R; Davis, PH; Sutton, LM; Anderson, RD; Chao, N; Rizzieri, DA
MLA Citation
Gasparet, C, Gockerman, JP, Diehl, LF, III, DCC, Moore, J, Long, GD, Horwitz, M, Chute, J, Sullivan, KM, Netuwirth, R, Davis, PH, Sutton, LM, Anderson, RD, Chao, N, and Rizzieri, DA. "Bortezomib Plus Melphalan and Prednisone as Induction Prior to Transplant or as Frontline Therapy for Non-Transplant Candidates in Patients with Previously Untreated Multiple Myeloma." BLOOD 112.11 (November 16, 2008): 1142-1142.
Source
wos-lite
Published In
Blood
Volume
112
Issue
11
Publish Date
2008
Start Page
1142
End Page
1142

Clinical and molecular predictors of disease severity and survival in chronic lymphocytic leukemia.

Several parameters may predict disease severity and overall survival in chronic lymphocytic leukemia (CLL). The purpose of our study of 190 CLL patients was to compare immunoglobulin heavy chain variable region (IgV(H)) mutation status, cytogenetic abnormalities, and leukemia cell CD38 and Zap-70 to older, traditional parameters. We also wanted to construct a simple, inexpensive prognosis score that would significantly predict TTT and survival in patients at the time of diagnosis and help practicing clinicians. In univariate analyses, patients with higher clinical stage, higher leukocyte count at diagnosis, shorter leukocyte doubling time, elevated serum lactate dehydrogenase (LDH), unmutated immunoglobulin heavy chain variable region (IgV(H)) genes, and higher CD38 had a shorter overall survival and time-to-treatment (TTT). CLL cell Zap-70 expression was higher in patients with unmutated IgV(H), and those with higher Zap-70 tended to have shorter survival. IgV(H)4-34 or IgV(H)1-69 was the most common IgV(H) genes used (16 and 12%, respectively). Of those with IgV(H)1-69, 86% had unmutated IgV(H) and had a significantly shorter TTT. A cytogenetic abnormality was noted in 71% of the patients tested. Patients with 11q22 del and 17p13 del or complex abnormalities were significantly more likely to have unmutated IgV(H). We found that a prognostic score constructed using modified Rai stage, cellular CD38, and serum LDH (parameters easily obtained clinically) significantly predicted TTT and survival in patients at the time of diagnosis and performed as well or better than models using the newer markers.

Authors
Weinberg, JB; Volkheimer, AD; Chen, Y; Beasley, BE; Jiang, N; Lanasa, MC; Friedman, D; Vaccaro, G; Rehder, CW; Decastro, CM; Rizzieri, DA; Diehl, LF; Gockerman, JP; Moore, JO; Goodman, BK; Levesque, MC
MLA Citation
Weinberg, JB, Volkheimer, AD, Chen, Y, Beasley, BE, Jiang, N, Lanasa, MC, Friedman, D, Vaccaro, G, Rehder, CW, Decastro, CM, Rizzieri, DA, Diehl, LF, Gockerman, JP, Moore, JO, Goodman, BK, and Levesque, MC. "Clinical and molecular predictors of disease severity and survival in chronic lymphocytic leukemia." Am J Hematol 82.12 (December 2007): 1063-1070.
PMID
17654680
Source
pubmed
Published In
American Journal of Hematology
Volume
82
Issue
12
Publish Date
2007
Start Page
1063
End Page
1070
DOI
10.1002/ajh.20987

Systemic interleukin-2 and adoptive transfer of lymphokine-activated killer cells improves antibody-dependent cellular cytotoxicity in patients with relapsed B-cell lymphoma treated with rituximab

Purpose: Murine models have shown that antibody-dependent cellular cytotoxicity (ADCC) can be improved with addition of lymphokine-activated killer (LAK) cells to monoclonal antibodies. A pilot trial of rituximab and LAK cells in patients with rituximab-refractory CD20+ lymphoma was conducted to evaluate this approach. Experimental Design: Ten patients received 3 million units/m2 of interleukin-2 (IL-2) i.v. qd on days 1 to 5 and leukapheresed on days 8, 9, and 10. The leukapheresis product was cultured with IL-2 for 48 h to produce LAK cells. Patients then received 375 mg/m2 i.v. rituximab and LAK cells on days 10, 11, and 12. The patients also received 3 million units/m2 of IL-2 i.v. for 5 days starting day 10. For safety purposes, the first three patients did not receive any LAK cell infusions. Results: The LAK cell infusions improved the ADCC activity of peripheral blood lymphocytes compared with pretreatment activity and prevented the decline in ADCC seen after infusion of rituximab alone. Therapy was well tolerated and the most clinically significant toxicities were fever and fatigue. Two patients achieved a partial remission and five had stable disease. Conclusions: The results from these studies suggest that the addition of LAK cells to rituximab augments ADCC in patients with rituximab-refractory lymphoma. © 2007 American Association for Cancer Research.

Authors
Berdeja, JG; Hess, A; Lucas, DM; O'Donnell, P; Ambinder, RF; Diehl, LF; Carter-Brookins, D; Newton, S; Flinn, IW
MLA Citation
Berdeja, JG, Hess, A, Lucas, DM, O'Donnell, P, Ambinder, RF, Diehl, LF, Carter-Brookins, D, Newton, S, and Flinn, IW. "Systemic interleukin-2 and adoptive transfer of lymphokine-activated killer cells improves antibody-dependent cellular cytotoxicity in patients with relapsed B-cell lymphoma treated with rituximab." Clinical Cancer Research 13.8 (2007): 2392-2399.
PMID
17438098
Source
scival
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
13
Issue
8
Publish Date
2007
Start Page
2392
End Page
2399
DOI
10.1158/1078-0432.CCR-06-1860

A phase I/II study examining pentostatin, chlorambucil, and theophylline in patients with relapsed chronic lymphocytic leukemia and non-Hodgkin's lymphoma

In an attempt to exploit bcl-2 overexpression and aberrant p53 function, two frequently encountered aberrations that predict marked treatment resistance and worse prognosis in patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL), we combined theophylline, pentostatin, and chlorambucil at two dose levels (cohort I: 30 mg/m2; cohort II: 20 mg/m2) on a 21-day cycle for up to six courses. We employed a phase I/II design to determine feasibility, define the maximum tolerated dose (MTD), and explore the impact of biologic modulation on response and time to progression (TTP) in 20 patients with relapsed or refractory CLL and NHL. Eight patients were enrolled in cohort I. They demonstrated a response rate (RR) of 28% and a 16.5-month TTP after receiving a median of two cycles. A 50% RR was observed in this cohort when patients with adverse histologies were excluded. Because of myelotoxicity, this dose level defined the MTD, and de-escalation occurred. All 12 patients in cohort II received 20 mg/m2 chlorambucil. A 50% RR and an 18-month TTP were observed after a median of 5.5 cycles. An RR of 47% and a complete remission (CR) of 5% were observed for the entire group, although responses and TTP varied greatly by histology. Significant activity was observed in patients with B-cell CLL and follicular lymphoma (FL). RR and TTP for fludarabine-sensitive/naïve and fludarabine-refractory (FR) B-cell CLL patients were 66 vs 25% and 20 vs 8.5 months, respectively. Both FL patients responded (one with partial remission and one with CR), with a 22.5-monthly median TTP. For responding patients, median TTP and overall survival (OS) was 21 and 69 months, respectively, compared to a median TTP of 2 months and an OS of 13.5 months for nonresponders. The combination of pentostatin, chlorambucil, and theophylline is the active regimen in patients with FL and B-cell CLL. © Springer-Verlag 2006.

Authors
Waselenko, JK; Reese, A; Park, K; Lucas, M; Goodrich, A; Willis, CR; Diehl, LF; Grever, MR; Byrd, JC; Flinn, IW
MLA Citation
Waselenko, JK, Reese, A, Park, K, Lucas, M, Goodrich, A, Willis, CR, Diehl, LF, Grever, MR, Byrd, JC, and Flinn, IW. "A phase I/II study examining pentostatin, chlorambucil, and theophylline in patients with relapsed chronic lymphocytic leukemia and non-Hodgkin's lymphoma." Annals of Hematology 85.5 (2006): 301-307.
PMID
16518606
Source
scival
Published In
Annals of Hematology
Volume
85
Issue
5
Publish Date
2006
Start Page
301
End Page
307
DOI
10.1007/s00277-005-0025-9

Outcomes of autologous and allogeneic blood or marrow transplantation for mantle cell lymphoma

To evaluate high-dose therapy and autologous or allogeneic blood or marrow transplantation (BMT) for mantle cell lymphoma, patients receiving BMT for newly diagnosed or relapsed mantle cell lymphoma were identified through the registry at Johns Hopkins. The pathologic diagnostic criteria were reviewed, and details of the presentation, transplant procedure, and survival outcomes were determined. Fifty-eight patients were identified, of whom 64% underwent transplantation in first remission and 12% had primary induction failure. Nineteen patients (one third) received an allograft. Preparative regimens consisted of cyclophosphamide in combination with either busulfan or total body irradiation. On multiple regression analysis, transplantation after 1 or more relapses (hazard ratio, 2.98; P = .02), primary induction failure (hazard ratio, 5.39; P = .002), and allogeneic transplantation (hazard ratio, 3.03; P = .007) were associated with an inferior event-free survival (EFS). However, EFS curves were not statistically different for autologous and allogeneic BMT performed in first remission, with an estimated 3-year EFS approaching or equaling 70%. Primary induction failure and residual bone marrow involvement were the only statistically significant predictors of relapse on multiple regression analysis. At 3 years, the estimated EFS for the entire cohort after BMT was 51%, the probability of relapse was 31%, and the overall survival was 59%. The benefit of autologous or allogeneic BMT for mantle cell lymphoma is thus most apparent when transplantation is performed in first remission. Whether allogeneic BMT ultimately confers an advantage because of a graft-versus-lymphoma effect remains to be determined. © 2005 American Society for Blood and Marrow Transplantation.

Authors
Kasamon, YL; Jones, RJ; Diehl, LF; Nayer, H; Borowitz, MJ; Garrett-Mayer, E; Ambinder, RF; Abrams, RA; Zhang, Z; Flinn, IW
MLA Citation
Kasamon, YL, Jones, RJ, Diehl, LF, Nayer, H, Borowitz, MJ, Garrett-Mayer, E, Ambinder, RF, Abrams, RA, Zhang, Z, and Flinn, IW. "Outcomes of autologous and allogeneic blood or marrow transplantation for mantle cell lymphoma." Biology of Blood and Marrow Transplantation 11.1 (2005): 39-46.
PMID
15625543
Source
scival
Published In
Biology of Blood and Marrow Transplantation
Volume
11
Issue
1
Publish Date
2005
Start Page
39
End Page
46
DOI
10.1016/j.bbmt.2004.09.007

Requirement for myeloid growth factors in the differentiation of acute promyelocytic leukaemia

It is well known that the differentiation of acute promyelocytic leukaemia (APL) cells by all-trans-retinoic acid (ATRA) may be enhanced by myeloid growth factors, but the requirement for growth factors in this process is unclear. Our previous studies in multiple myeloma and non-APL acute myeloid leukaemia demonstrated that lineage-specific growth factors are required for the maximal activity of many pharmacologic differentiating agents in vitro. Thus, we studied whether the differentiation of APL is similarly dependent on growth factors. We found that the myeloid growth factors granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor markedly increased the differentiation of NB4 cells or APL blasts from clinical samples treated with ATRA, arsenic trioxide (ATO), or bryostatin-1 as evidenced by the enhanced expression of myeloid surface antigens and the inhibition of clonogenic growth. Furthermore, myeloid growth factors were necessary for the differentiation of APL cells since the activity of each pharmacologic agent could be blocked by specific growth factor-neutralizing antibodies. Each differentiating agent was active only at concentrations that inhibited cell cycling, suggesting that this property is also required for differentiation. These data demonstrate that both pharmacologic differentiating agents and myeloid growth factors are required, but neither sufficient, for the differentiation of APL cells. The combined use of pharmacologic differentiating agents and growth factors may improve the clinical efficacy of differentiation therapy in APL. © 2005 Blackwell Publishing Ltd.

Authors
Matsui, W; Smith, BD; Vala, M; Beal, N; Huff, CA; Diehl, LF; Jones, RJ
MLA Citation
Matsui, W, Smith, BD, Vala, M, Beal, N, Huff, CA, Diehl, LF, and Jones, RJ. "Requirement for myeloid growth factors in the differentiation of acute promyelocytic leukaemia." British Journal of Haematology 128.6 (2005): 853-862.
PMID
15755292
Source
scival
Published In
British Journal of Haematology
Volume
128
Issue
6
Publish Date
2005
Start Page
853
End Page
862
DOI
10.1111/j.1365-2141.2005.05395.x

Phase I study of low-dose interleukin-2, fludarabine, and cyclophosphamide for previously untreated indolent lymphoma and chronic lymphocytic leukemia

Purpose: Fludarabine and cyclophosphamide is an effective combination but increases the risk of opportunistic infections due to depressed lymphocyte counts. In an attempt to preserve CD4 counts, we conducted a phase I, double-blind, placebo-controlled trial of recombinant interleukin-2 (IL-2) added to fludarabine and cyclophosphamide in patients with treatment-naive indolent lymphomas or chronic lymphocytic leukemia. Experimental Design: Subcutaneous IL-2 (days 1-21 of each 28-day cycle) was combined with cyclophosphamide (600 mg/m2, day 8) and fludarabine (20 mg/m2, days 8-12) at four dose levels: 0.8, 1.0, 1.2, and 1.4 × 106 IU/m 2/d. IL-2 dose was escalated in cohorts of four to six patients, with one patient per cohort receiving placebo. Results: Twenty-three patients, median age 50, were enrolled, of whom 30% had chronic lymphocytic leukemia/small lymphocytic lymphoma and 52% had follicular lymphomas. The combination was generally well tolerated, with mainly hematologic toxicities. CD4 counts typically declined substantially during the early weeks of treatment and remained suppressed for months afterward. In the 18 evaluable patients who received IL-2, the mean absolute CD4 count was 999 cells/μL (range, 97-3,776) pretreatment, 379 cells/μL (range, 54-2,599) at day 14, and 98 cells/μL (range, 17-291) at end of treatment. In longitudinal linear models, the changes in CD4 counts were not significantly different across IL-2 dose levels. Conclusions:The addition of low-dose IL-2 to fludarabine and cyclophosphamide does not seem immunoprotective. New approaches are needed to reduce the cellular immunosuppression and infectious complications associated with purine analogues. © 2005 American Association for Cancer Research.

Authors
Kasamon, YL; Flinn, IW; Grever, MR; Diehl, LF; Garrett-Mayer, E; Goodman, SN; Lucas, MS; Byrd, JC
MLA Citation
Kasamon, YL, Flinn, IW, Grever, MR, Diehl, LF, Garrett-Mayer, E, Goodman, SN, Lucas, MS, and Byrd, JC. "Phase I study of low-dose interleukin-2, fludarabine, and cyclophosphamide for previously untreated indolent lymphoma and chronic lymphocytic leukemia." Clinical Cancer Research 11.23 (2005): 8413-8417.
PMID
16322303
Source
scival
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
11
Issue
23
Publish Date
2005
Start Page
8413
End Page
8417
DOI
10.1158/1078-0432.CCR-05-1612

Long-term follow-up of T cell-depleted allogeneic bone marrow transplantation in refractory multiple myeloma: Importance of allogeneic T cells

Multiple myeloma may be cured by myeloablative conditioning and allogeneic blood or marrow transplantation (alloBMT), but this occurs at the expense of high transplant-related mortality. In an endeavor to reduce procedure-related toxicity, this study retrospectively evaluated the safety, tolerability, and efficacy of T cell depletion by counterflow centrifugal elutriation before alloBMT. Fifty-one patients with stage II (6) or III (45) multiple myeloma received alloBMTs using T cell depletion by elutriation. Fifty-three percent (27 of 51) of patients had primary refractory disease at the time of transplantation, 10% (5 of 51) had relapsed disease, and 4% (2 of 51) had refractory relapsed disease. The median age was 49 (range, 32 to 62) years, and the median time from diagnosis to transplantation was 9 (range, 4 to 58) months. Patients had received a median of 1 (range, 1 to 3) regimen and 4 (range, 2 to 16) cycles of chemotherapy. In this population, transplant-related mortality rate was 24% (12 of 51) with 2 patients dying of graft-versus-host disease (GVHD). Thirty-one of 39 evaluable patients have experienced relapse, and the probability of progression-free survival 5 years after alloBMT alone is 16%. Sixteen patients were given donor lymphocyte infusions (DLI) at the time of relapse (n = 11) or for persistent disease 1 year after transplantation (n = 5). Acute or chronic GVHD was seen in 63% (10 of 16) of patients given DLI. Responses were seen in 8 of 16 patients (6 complete response [CR], 2 partial response [PR]) with 6 of 8 responding patients having GVHD. Five recipients of DLI remain in a continuous CR, ranging from 3 to 64 months in duration. Thus, like chronic myelogenous leukemia, allogeneic T cells appear to have potent antimyeloma activity that is critical for achieving a cure. DLI-induced remissions of multiple myeloma can be durable, even in patients with refractory multiple myeloma. Unlike chronic myelogenous leukemia, the antimyeloma effect of allogeneic T cells rarely occurs in the absence of clinically significant GVHD. © 2003 American Society for Blood and Marrow Transplantation.

Authors
Huff, CA; Fuchs, EJ; Noga, SJ; O'Donnell, PV; Ambinder, RF; Diehl, L; Borrello, I; Vogelsang, GB; Miller, CB; Flinn, IA; Brodsky, RA; Marcellus, D; Jones, RJ
MLA Citation
Huff, CA, Fuchs, EJ, Noga, SJ, O'Donnell, PV, Ambinder, RF, Diehl, L, Borrello, I, Vogelsang, GB, Miller, CB, Flinn, IA, Brodsky, RA, Marcellus, D, and Jones, RJ. "Long-term follow-up of T cell-depleted allogeneic bone marrow transplantation in refractory multiple myeloma: Importance of allogeneic T cells." Biology of Blood and Marrow Transplantation 9.5 (2003): 312-319.
PMID
12766881
Source
scival
Published In
Biology of Blood and Marrow Transplantation
Volume
9
Issue
5
Publish Date
2003
Start Page
312
End Page
319
DOI
10.1016/S1083-8791(03)00075-2

Leukemia cutis in a patient with chronic neutrophilic leukemia

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative disorder. Less than 50 cases have been reported. We report the first case of CNL with an associated leukemia cutis. CNL was diagnosed in a 74-year-old white woman in 1998, based on neutrophilic infiltration of the bone marrow and absence of the Philadelphia chromosome. The patient presented to the dermatology service in August 1998 with a 2 week history of a pruritic eruption on the arms, hands, and legs. Physical examination revealed red to violaceous plaques on both thighs and knees, in addition to purpuric patches and plaques on the dorsal hands, arms, and legs. Leukemia cutis was demonstrated on biopsy specimens of several lesional sites. The eruption progressed, despite treatment with topical and systemic corticosteroids. Treatment with systemic chemotherapy did affect partial resolution of the eruption, with parallel decreases in bone pain and white blood cell count, but the disease progressed and the patient ultimately died 5 months after her initial skin findings. Only one other case of CNL with dermatologic manifestations has been reported, CNL associated with a reactional neutrophilic dermatosis. Comparison to and differentiation from this case is discussed. The importance of distinguishing the specific infiltrates of leukemia from the nonspecific infiltrates of reactional dermatoses, such as Sweet's syndrome, is illustrated.

Authors
Willard, RJ; Turiansky, GW; Genest, GP; Davis, BJ; Diehl, LF
MLA Citation
Willard, RJ, Turiansky, GW, Genest, GP, Davis, BJ, and Diehl, LF. "Leukemia cutis in a patient with chronic neutrophilic leukemia." Journal of the American Academy of Dermatology 44.2 SUPPL. (2001): 365-369.
PMID
11174417
Source
scival
Published In
Journal of The American Academy of Dermatology
Volume
44
Issue
2 SUPPL.
Publish Date
2001
Start Page
365
End Page
369
DOI
10.1067/mjd.2001.103996

Life expectancy benefits of cancer screening in the end-stage renal disease population

Health maintenance includes secondary prevention through cancer screening. There are no established guidelines for cancer screening patients with end-stage renal disease (ESRD). Using an established method of estimating life expectancy, published literature on cancer screening, and information from databases on mortality and malignancy (US Renal Data System 1997 Annual Data Report and the SEER Cancer and Statistical Review, 1973- 1994), a 'real-time life expectancy calculator' was developed to guide the primary help provider in making informed decisions on the benefits of cancer screening in individual patients. Potential days of life saved by each screening method can be calculated using the difference in life expectancy per the DEALE (declining exponential approximation of life expectancy) method with and without cancer screening. Using two sets of assumptions (one to enhance any bias toward support for screening and one to limit this bias), a range of potential days of life saved with screening for breast and colon cancer can be calculated in individual patients with ESRD. In breast cancer, for example, a 50-year-old black woman with ESRD and multiple risk factors would have 41 to 291 potential days of life saved with screening. A 60-year- old white woman with ESRD and diabetes mellitus (DM) would have only 1 to 16 days of life saved. This life expectancy calculator can guide the primary health care provider in making clinical decisions concerning screening in the ESRD population. In addition to assisting in patient education, the calculator can be updated as new information becomes available regarding relative risk, treatment, and mortality.

Authors
LeBrun, CJ; Diehl, LF; Abbott, KC; Welch, PG; Yuan, CM
MLA Citation
LeBrun, CJ, Diehl, LF, Abbott, KC, Welch, PG, and Yuan, CM. "Life expectancy benefits of cancer screening in the end-stage renal disease population." American Journal of Kidney Diseases 35.2 (2000): 237-243.
PMID
10676722
Source
scival
Published In
American Journal of Kidney Diseases
Volume
35
Issue
2
Publish Date
2000
Start Page
237
End Page
243

Fludarabine and cyclophosphamide with filgrastim support in patients with previously untreated indolent lymphoid malignancies

To evaluate the response rate and potential toxicities, a phase II trial was conducted of fludarabine and cyclophosphamide with filgrastim support in patients with previously untreated low-grade and select intermediate-grade lymphoid malignancies. Symptomatic patients with preserved end organ function received cyclophosphamide 600 mg/m2 intravenous (iv) day 1 and fludarabine 20 mg/m2 iv days1 through 5, followed by filgrastim 5 μg/kg subcutaneous starting approximately day 8. Treatment was repeated every 28 days until maximum response or a maximum of 6 cycles. Sixty patients, median age 53.5 years, were enrolled. Thirty-seven patients with non-Hodgkin lymphoma (NHL) were stage IV and 6 were stage III. Eleven of 17 patients with chronic lymphocytic leukemia (CLL) were Rai intermediate risk and 6 were high risk. The overall complete response (CR) rate was 51% and the partial response (PR) rate was 41%. Of patients with CLL, 47% achieved a CR and the remaining 53% achieved a PR. Of patients with follicular lymphoma, 60% achieved CR and 32% achieved a PR. Although the toxicity of this regimen was mainly hematologic, significant nonhematologic toxicities, including infections, were seen. Twenty-four patients subsequently received an autologous or allogeneic stem cell transplant. Engraftment was rapid, and there were no noticeable procedure toxicities in the immediate posttransplant period attributable to the fludarabine and cyclophosphamide regimen. Fludarabine, cyclophosphamide, and filgrastim make up a highly active and well-tolerated regimen in CLL and NHL. (C) 2000 by The American Society of Hematology.

Authors
Flinn, IW; Byrd, JC; Morrison, C; Jamison, J; Diehl, LF; Murphy, T; Piantadosi, S; Seifter, E; Ambinder, RF; Vogelsang, G; Grever, MR
MLA Citation
Flinn, IW, Byrd, JC, Morrison, C, Jamison, J, Diehl, LF, Murphy, T, Piantadosi, S, Seifter, E, Ambinder, RF, Vogelsang, G, and Grever, MR. "Fludarabine and cyclophosphamide with filgrastim support in patients with previously untreated indolent lymphoid malignancies." Blood 96.1 (2000): 71-75.
PMID
10891432
Source
scival
Published In
Blood
Volume
96
Issue
1
Publish Date
2000
Start Page
71
End Page
75

A dose-finding study of liposomal daunorubicin with CVP (COP-X) in advanced NHL

Background: Standard therapy for lymphoma consists of a cyclophosphamide (C), doxorubicin, vincristine (V), and prednisone (P) (CHOP) combination regimen. Liposomal daunorubicin (DaunoXome®) is an alternative to doxorubicin for patients with lymphoma because of its more favorable safety profile and potentially more selective uptake in lymphoma. The objectives of this study were to determine the maximum tolerated dose (MTD) of liposomal daunorubucin with CVP (COP-X) and the tolerability of the regimen in patients with indolent lymphoma. Patients and methods: Patients with low-grade and intermediate-grade lymphoma having adequate cardiac, hepatic, and renal function were enrolled. Patients received C 750 mg/m2, V 1.4 mg/m2 (maximum 2.0 mg), and liposomal daunorubicin 50-100 mg/m2 i.v. on day 1 and P 100 mg p.o. on days 1-5. MTD was the liposomal daunorubicin dose associated with 20% dose-limiting toxicity (ANC < 500/mm3 for > 5 days or febrile neutropenia). Results: Twenty patients, median age 59 years, were treated. The liposomal daunorubicin MTD combined with CVP was 70-80 mg/m2, depending on patient population. No significant non-hematologic toxicity occurred. Response rate was 44% (2 complete and 5 partial responses). Conclusions: A liposomal daunorubicin dose of 80 mg/m2 in the COP-X regimen was well tolerated with little non-hematologic toxicity.

Authors
Flinn, IW; Goodman, SN; Post, L; Jamison, J; Miller, CB; Gore, S; Diehl, L; Willis, C; Ambinder, RF; Byrd, JC
MLA Citation
Flinn, IW, Goodman, SN, Post, L, Jamison, J, Miller, CB, Gore, S, Diehl, L, Willis, C, Ambinder, RF, and Byrd, JC. "A dose-finding study of liposomal daunorubicin with CVP (COP-X) in advanced NHL." Annals of Oncology 11.6 (2000): 691-695.
PMID
10942057
Source
scival
Published In
Annals of Oncology
Volume
11
Issue
6
Publish Date
2000
Start Page
691
End Page
695
DOI
10.1023/A:1008361914894

The national cancer data base report on age, gender, treatment, and outcomes of patients with chronic lymphocytic leukemia

BACKGROUND. The natural history of chronic lymphocytic leukemia (CLL) is changing, although the reasons (potential changes in the disease's biology or in patterns in patient characteristics, treatment, or referral) are unclear. METHODS. This report uses National Cancer Data Base (NCDB) data, which reflect a hospital-based patient population from a broad spectrum of hospitals in the United States. Age, gender, race/ethnicity, income, treatment, overall survival, and relative survival were evaluated according to time period (1985-1990 and 19911995). Comparisons were made with U.S. population figures for 1990 and with series published over the last 70 years. RESULTS. CLL comprised 22.6% of the 108,396 cases of leukemia in the data base. The risk of developing CLL increased progressively with age and did not plateau; the average age was 69.6 years. At the time of initial diagnosis, 60.5% of patients received no treatment (this proportion increased from 58.1% to 62.7% between the 2 time periods). Overall survival was 48.2% at 5 years and 22.5% at 10 years. The 5-year relative survival was 69.5%, 72.2%, 63.1%, and 41.7% for age groups <40, 40-59, 60-79, and 80+ years, respectively; these rates indicated that CLL, and not comorbid disease, caused the greatest percentage of deaths. CONCLUSIONS. The risk of developing CLL increases progressively with age without plateauing and is 2.8 times higher for older men than for older women. There is an increasing trend toward no treatment at the time of initial diagnosis. Long term overall survival of CLL patients is poor. CLL is a more fatal disease among older individuals because of the disease itself, not because of comorbid conditions.

Authors
Diehl, LF; Karnell, LH; Menck, HR
MLA Citation
Diehl, LF, Karnell, LH, and Menck, HR. "The national cancer data base report on age, gender, treatment, and outcomes of patients with chronic lymphocytic leukemia." Cancer 86.12 (1999): 2684-2692.
PMID
10594864
Source
scival
Published In
Cancer
Volume
86
Issue
12
Publish Date
1999
Start Page
2684
End Page
2692

Herpes virus infections occur frequently following treatment with fludarabine: Results of a prospective natural history study

We performed a prospective infectious natural history study of 21 patients with low-grade lymphoproliferative disorders receiving fludarabine as initial (n=5) or salvage (n = 16) therapy. 12 (57%) of these patients developed herpes zoster (n = 9), herpes simplex I (n = 1) or herpes simplex II (n= 2) infections at a median of 8 (range 1-17) months following initiation of fludarabine, with 75% of these having completed therapy. All patients with herpes zoster developed severe post-herpetic neuralgia. Factors differentiating patients developing these infections included older age and low serum IgG or IgA. Based upon these prospective data, we conclude that herpes virus infections frequently occur following fludarabine treatment, necessitating aggressive patient education and new prophylactic strategies.

Authors
Byrd, JC; McGrail, LH; Hospenthal, DR; Howard, RS; Dow, NA; Diehl, LF
MLA Citation
Byrd, JC, McGrail, LH, Hospenthal, DR, Howard, RS, Dow, NA, and Diehl, LF. "Herpes virus infections occur frequently following treatment with fludarabine: Results of a prospective natural history study." British Journal of Haematology 105.2 (1999): 445-447.
PMID
10233419
Source
scival
Published In
British Journal of Haematology
Volume
105
Issue
2
Publish Date
1999
Start Page
445
End Page
447

D-dimer assay predicts mortality in critically ill patients without disseminated intravascular coagulation or venous thromboembolic disease

Objective: To determine if D-dimer predicts outcomes in critically ill patients. Design: Observational, cohort study. Setting: Medical intensive care unit (MICU) of a tertiary care hospital. Patients and participants: Seventy-four patients consecutively admitted to the MICU. Interventions: D-dimer was measured by latex agglutination within 12 h of admission to the MICU. Measurements and results: Of the study population, 43.2% had positive D-dimers. The in-hospital mortality rate in D-dimer positive patients was 28.1% as compared to 7.1% in D-dimer negative subjects (p = 0.024). D-dimer positive patients had significantly greater frequencies of venous thromboses (21.9% vs 4.8%, p = 0.035). Conclusions: The D-dimer assay identifies patients at increased risk for mortality and may be a more sensitive test to determine the presence of underlying microvascular pathology in critically ill patients. A positive D-dimer at admission to the MICU is associated with an increased risk for the later development of a venous thromboembolic event (VTE).

Authors
Shorr, AF; Trotta, RF; Alkins, SA; Hanzel, GS; Diehl, LF
MLA Citation
Shorr, AF, Trotta, RF, Alkins, SA, Hanzel, GS, and Diehl, LF. "D-dimer assay predicts mortality in critically ill patients without disseminated intravascular coagulation or venous thromboembolic disease." Intensive Care Medicine 25.2 (1999): 207-210.
PMID
10193549
Source
scival
Published In
Intensive Care Medicine
Volume
25
Issue
2
Publish Date
1999
Start Page
207
End Page
210
DOI
10.1007/s001340050817

Comparison of psychosocial adaptation of advanced stage Hodgkin's disease and acute leukemia survivors. Cancer and Leukemia Group B.

BACKGROUND: The purpose of this study was to compare the long-term psychosocial adaptation of Hodgkin's disease and adult acute leukemia survivors. PATIENTS AND METHODS: Two hundred seventy-three Hodgkin's disease (HD) and 206 adult acute leukemia (AL) survivors were interviewed by telephone concerning their psychosocial adjustment and problems they attributed to having been treated for cancer, using identical research procedures and a common set of instruments. The following measures were used: Psychosocial Adjustment to Illness Scale (PAIS); Brief Symptom Inventory (BSI); current Conditioned Nausea and Vomiting triggered by treatment-related stimuli (CNVI); Indices of Employment, Insurance and Sexual Problems Attributed to Cancer; Negative Socioeconomic Impact of Cancer Index (NSI). All participants had been treated on one of nine Hodgkin's disease or 13 acute leukemia Cancer and Leukemia Group B (CALGB) clinical trials from 1966-1988, and had been off treatment for one year or more (mean years: HD = 5.9; AL = 5.6). RESULTS: HD survivors' risk of having a high distress score on the BSI was almost twice that found for AL survivors (odds ratio = 1.90), with 21% of HD vs. 14% of AL survivors (P < 0.05) having scores that were 1.5 standard deviations above the norm, suggestive of a possible psychiatric disorder. HD survivors reported greater fatigue (POMS Fatigue, P = 0.01; Vigor Subscales, P = 0.001), greater conditioned nausea (CNVI, P < 0.05), greater impact of cancer on their family life (PAIS Domestic Environment, P = 0.004) and poorer sexual functioning (PAIS Sexual Relationships, P = 0.0001), than AL survivors. CONCLUSIONS: Treatment-related issues may have placed HD survivors at a greater risk for problems in long-term adaptation than AL survivors.

Authors
Kornblith, AB; Herndon, JE; Zuckerman, E; Cella, DF; Cherin, E; Wolchok, S; Weiss, RB; Diehl, LF; Henderson, E; Cooper, MR; Schiffer, C; Canellos, GP; Mayer, RJ; Silver, RT; Schilling, A; Peterson, BA; Greenberg, D; Holland, JC
MLA Citation
Kornblith, AB, Herndon, JE, Zuckerman, E, Cella, DF, Cherin, E, Wolchok, S, Weiss, RB, Diehl, LF, Henderson, E, Cooper, MR, Schiffer, C, Canellos, GP, Mayer, RJ, Silver, RT, Schilling, A, Peterson, BA, Greenberg, D, and Holland, JC. "Comparison of psychosocial adaptation of advanced stage Hodgkin's disease and acute leukemia survivors. Cancer and Leukemia Group B." Ann Oncol 9.3 (March 1998): 297-306.
PMID
9602264
Source
pubmed
Published In
Annals of Oncology
Volume
9
Issue
3
Publish Date
1998
Start Page
297
End Page
306

Hemolytic anemia after fludarabine therapy for chronic lymphocytic leukemia

Purpose: A report of the clinical features, treatment, and outcome of patients who developed hemolytic anemia (HA) temporally associated with fludarabine (Fludara; Berlex Laboratories, Richmond, CA) therapy for chronic lymphocytic leukemia (CLL). Patients and Methods: Data on 24 patients who developed HA related to fludarabine therapy were collected from the Spontaneous Reporting System of the Food and Drug Administration (FDA) and the Walter Reed Army Medical Center (Washington, DC). Results: Seventeen (71%) patients developed HA after either the first, second, or third cycle of this drug. The longest duration of fludarabine therapy before HA occurred was six cycles. The median decline in hematocrit from baseline during the hemolytic episode was 14.1 (range, 8.0 to 28.9) for the 18 patients for whom this information was available. For the 11 patients for whom transfusion requirements were known, the number of transfusions administered ranged between three and 36. Seven (29%) patients died of medical complications associated with the HA. Seven of eight patients who were re-challenged with fludarabine after an episode of HA developed recurrent HA, and three of these patients died. Conclusion: HA associated with fludarabine therapy appears to be uncommon, but it can be severe and fatal, especially if a patient is re- treated with this drug after a previous episode of HA. The mechanism of this toxicity is unknown, but it may be caused by the release of a suppressed auto-antibody to a native red cell antigen.

Authors
Weiss, RB; Freiman, J; Kweder, SL; Diehl, LF; Byrd, JC
MLA Citation
Weiss, RB, Freiman, J, Kweder, SL, Diehl, LF, and Byrd, JC. "Hemolytic anemia after fludarabine therapy for chronic lymphocytic leukemia." Journal of Clinical Oncology 16.5 (1998): 1885-1889.
PMID
9586905
Source
scival
Published In
Journal of Clinical Oncology
Volume
16
Issue
5
Publish Date
1998
Start Page
1885
End Page
1889

Flavopiridol induces apoptosis in chronic lymphocytic leukemia cells via activation of caspase-3 without evidence of bcl-2 modulation or dependence on functional p53

Flavopiridol has been reported to induce apoptosis in lymphoid cell lines via downregulation of bcl-2. The in vitro activity of flavopiridol against human chronic lymphocytic leukemia (CLL) cells and potential mechanisms of action for inducing cytotoxicity were studied. The in vitro viability of mononuclear cells from CLL patients (n = 11) was reduced by 50% at 4 hours, 24 hours, and 4 days at a flavopiridol concentration of 1.15 μmol/L (95% confidence interval [CI] ± 0.31), 0.18 μmol/L (95% CI ±0.04), and 0.16 μmol/L (95% CI ± 0.04), respectively. Loss of viability in human CLL cells correlated with early induction of apoptosis. Exposure of CLL cells to 0.18 μmol/L of flavopiridol resulted in both decreased expression of p53 protein and cleavage of the caspase-3 zymogen 32-kD protein with the appearance of its 20-kD subunit. Contrasting observations of others in tumor cell lines, flavopiridol cytotoxicity in CLL cells did not correlate with changes in bcl-2 protein expression alterations. We evaluated flavopiridol's dependence on intact p53 by exposing splenocytes from wild-type (p53(+/+)) and p53 null (p53(-/-)) mice that demonstrated no preferential cytotoxicity as compared with a marked differential with F-ara-a and radiation. Incubation of CLL cells with antiapoptotic cytokine interleukin-4 (IL-4) did not alter the LC50 of flavopiridol, as compared with a marked elevation noted with F- ara-a in the majority of patients tested. These data demonstrate that flavopiridol has significant in vitro activity against human CLL cells through activation of caspase-3, which appears to occur independently of bcl- 2 modulation, the presence of IL-4, or p53 status. Such findings strongly support the early introduction of flavopiridol into clinical trials for patients with B-CLL.

Authors
Byrd, JC; Shinn, C; Waselenko, JK; Fuchs, EJ; Lehman, TA; Nguyen, PL; Flinn, IW; Diehl, LF; Sausville, E; Grever, MR
MLA Citation
Byrd, JC, Shinn, C, Waselenko, JK, Fuchs, EJ, Lehman, TA, Nguyen, PL, Flinn, IW, Diehl, LF, Sausville, E, and Grever, MR. "Flavopiridol induces apoptosis in chronic lymphocytic leukemia cells via activation of caspase-3 without evidence of bcl-2 modulation or dependence on functional p53." Blood 92.10 (1998): 3804-3816.
PMID
9808574
Source
scival
Published In
Blood
Volume
92
Issue
10
Publish Date
1998
Start Page
3804
End Page
3816

Transient abnormalities in serum bilirubin and lactate dehydrogenase levels following red blood cell transfusions in adults

BACKGROUND: The effect of transfusion of small amounts of packed red blood cells (PRBC) on serum chemistry values is not known. METHODS: We studied 73 adult patients without evidence of bleeding who received 2-unit PRBC transfusions. In study 1 (n = 39), we examined multiple laboratory values pretransfusion and 15 minutes, 1 hour, 2 hours, and 24 hours posttransfusion. In study 2 (n = 34), we examined changes in fractionated bilirubin, lactate dehydrogenase, and haptoglobin prior to and 1 hour following the transfusion. RESULTS: Total bilirubin increased from a median pretransfusion baseline of 0.7 mg/dL to 1.4 mg/dL shortly after transfusion (P <0.0005), and then returned to normal 24 hours later. Of the 36 patients with normal pretreatment total bilirubin levels, 17 (47%) became transiently abnormal. The lactate dehydrogenase level increased similarly 15 minutes after transfusion, but returned to baseline 24 hours later. The unconjugated bilirubin level increased from a median baseline pretransfusion value of 0.3 mg/dL to 1.1 mg/dL at 1 hour posttransfusion (P <0.0005). No significant changes were noted in conjugated bilirubin levels or haptoglobin concentration following transfusion. CONCLUSIONS: Transient increases in serum bilirubin and lactate dehydrogenase are seen following transfusion of PRBC. These data should be considered when interpreting laboratory values during the first few hours after a transfusion.

Authors
Wiesen, AR; Byrd, JC; Hospenthal, DR; Howard, RS; Shorr, AR; Glass, KL; Diehl, LF
MLA Citation
Wiesen, AR, Byrd, JC, Hospenthal, DR, Howard, RS, Shorr, AR, Glass, KL, and Diehl, LF. "Transient abnormalities in serum bilirubin and lactate dehydrogenase levels following red blood cell transfusions in adults." American Journal of Medicine 104.2 (1998): 144-147.
PMID
9528732
Source
scival
Published In
The American Journal of Medicine
Volume
104
Issue
2
Publish Date
1998
Start Page
144
End Page
147
DOI
10.1016/S0002-9343(97)00398-7

Autoimmune disease and chronic lymphocytic leukemia: Autoimmune hemolytic anemia, pure red cell aplasia, and autoimmune thrombocytopenia

Immune dysregulation, a hallmark of chronic lymphocytic leukemia (CLL), manifests itself in three autoimmune diseases: warm autoimmune hemolytic anemia (AIHA); idiopathic thrombocytopenia (ITP); and, pure red cell aplasia (PRCA). AIHA occurs in 11% of advanced stage CLL patients. Prednisone is the first treatment of choice, with 90% responses and 65% complete responses. More than 60% of patients relapse when treatment is stopped. Intravenous immunoglobulin, the next line of treatment, causes responses in 40% of patients. While the data are very limited, cyclosporine A is a reasonable choice for third-line therapy. Alkylating agents, danazol, plasma exchange, immuno-absorption, vincristine-loaded platelets, splenectomy, and splenic irradiation are also reported to cause responses. The data on mechanisms of AIHA are most consistent with immune dysregulation leading to loss of tolerance to a self antigen which in turn leads to the immune-based hemolytic anemia. PRCA is underrecognized in CLL with 6% of CLL patients having PRCA when tested for it. Unlike AIHA, PRCA often occurs in early stage disease. Anemia, reticulocytopenia, and a marrow virtually devoid of red blood cell precursors are hallmarks of PRCA. Corticosteroid therapy is the first line of treatment. If a response is not obtained in 4 weeks, cyclosporine A should be added. Although the data on pathophysiology are very limited, PRCA appears to be the result of an abnormal T cell that both falls in its normal function to support growth and inhibits the growth of erythroid progenitor cells. ITP occurs in 2-3% of CLL patients, occurs in early stage disease and may be a presenting manifestation. Initial therapy for ITP mirrors the guidelines for primary ITP. Initial therapy should consist of prednisone. Seventy percent of patients respond. Splenectomy is a reasonable second-line treatment. Autoimmune phenomena, largely related to blood cells, are based in the immune dysregulation of CLL. Longer survivals in CLL patients, more treatment regimens per patient, and more immunosuppression with modern treatments, allow us to predict an increasing incidence of autoimmune blood cell diseases in CLL.

Authors
Diehl, LF; Ketchum, LH
MLA Citation
Diehl, LF, and Ketchum, LH. "Autoimmune disease and chronic lymphocytic leukemia: Autoimmune hemolytic anemia, pure red cell aplasia, and autoimmune thrombocytopenia." Seminars in Oncology 25.1 (1998): 80-97.
PMID
9482530
Source
scival
Published In
Seminars in Oncology
Volume
25
Issue
1
Publish Date
1998
Start Page
80
End Page
97

Hodgkin's disease treated with neck radiation is associated with increased antibody-dependent cellular cytotoxicity against human extraocular muscle cells

Patients with Hodgkin's disease have higher a prevalence of thyroid function abnormalities and, perhaps, orbitopathy than the general population, but the pathophysiology of this association and its relationship to Hodgkin's disease treatment remain unclear. We analyzed the frequency of thyroid function abnormalities, autoantibodies against thyroid antigens, and autoimmunity against extraocular muscle cell antigens by Western blot analyses and antibody-dependent cellular cytotoxicity (ADCC) assays in patients with Hodgkin's disease (n = 20) and controls (n = 10). Hodgkin's disease patients were subdivided into those treated with thyroidal external beam radiation therapy (XRT, n = 15) or chemotherapy (MOPP/ABVD, n = 5). The ADCC assay against extraocular muscle cells was increased in patients with Hodgkin's disease (5.5% vs. <1.0%, p = .026) when compared with controls. In addition, Hodgkin's disease patients treated with XRT (with or without chemotherapy) had significantly higher ADCC tests than controls (9.7% vs. <1.0%, p = .010). In contrast, ADCC assays were not different between Hodgkin's disease patients treated with chemotherapy alone and controls (<1.0% vs. <1.0%, p = .53). Hodgkin's patients treated with XRT had higher ADCC assays than those treated with chemotherapy alone (p = .087), although this difference did not achieve statistical significance. Serum measurements of antithyroid peroxidase (TPO) antibodies, antithyroglobulin (Tg) antibodies, thyroid binding inhibitory immunoglobulins (TBII), and thyroid stimulating immunoglobulin (TSI) were similar in all groups. Antibodies against the 64 kDa orbital antigen were detected in 1 patient and 1 control subject. Excluding patients already treated with L-thyroxine for hypothyroidism (n = 5), free T3, but not free T4, was lower in the Hodgkin's disease group than in controls (2.2 pg/mL vs. 2.7 pg/mL, p = .008). Thyrotropin (TSH) concentrations were not statistically different between these groups. In summary, these data show: (1) ADCC against human orbital muscle cells is increased in patients with Hodgkin's disease compared with controls: (2) these differences were noted among Hodgkin's disease patients treated with thyroidal XRT, with or without chemotherapy, and not among those patients treated with chemotherapy alone; and (3) no statistically significant differences in the frequency of thyroid autoantibodies were found. These data suggest that patients with Hodgkin's disease display altered antibody-dependent immune function toward extraocular muscle cells that may possibly be related to by XRT. Larger, prospective studies assessing thyroid and orbital-related immunologic abnormalities in Hodgkin's disease are warranted.

Authors
Ringel, MD; Taylor, T; Barsouk, A; Wall, JR; Freter, CE; Howard, RS; Diehl, L; Burman, KD
MLA Citation
Ringel, MD, Taylor, T, Barsouk, A, Wall, JR, Freter, CE, Howard, RS, Diehl, L, and Burman, KD. "Hodgkin's disease treated with neck radiation is associated with increased antibody-dependent cellular cytotoxicity against human extraocular muscle cells." Thyroid 7.3 (1997): 425-432.
PMID
9226215
Source
scival
Published In
Thyroid
Volume
7
Issue
3
Publish Date
1997
Start Page
425
End Page
432

Detection of Epstein-Barr virus in transformations of low-grade B-cell lymphomas after fludarabine treatment

Fludarabine is a highly effective chemotherapeutic agent for chronic lymphocytic leukemia/small lymphocytic lymphoma and is also active in other B-cell lymphoproliferative disorders. Although highly efficacious in destroying the malignant B-cells, fludarabine also causes T-cell lymphopenia and immunosuppression. We present five patients given fludarabine for low- grade B-cell lymphoproliferafive disorders who showed transformation of the primary neoplasm to a higher grade tumor. Immunohistologic antibody studies were performed on paraffin-embedded tissue sections of the initial tissue (when available) and on the follow-up biopsy specimens for CD20, CD3, CD45RO, CD43, CD30, CD15, and latent membrane protein (LMP-1) for Epstein-Barr virus (EBV). The initial diagnoses in these five patients included chronic lymphocytic leukemia/small lymphocytic lymphoma (three cases), follicle center lymphoma (one case), and Waldenstrom's macroglobulinemia (one case). All of the follow-up biopsy specimens showed scattered Hodgkin's-like cells, and two of the five also showed loci of large-cell transformation. The Hodgkin's-like cells showed CD30 immunoreactivity in four of the five cases and CD15 immunoreactivity in three of the five. Strong immunoreactivity of the large, atypical, Hodgkin's-like cells for LMP-1 of EBV was noted in four cases; in the remaining case, this finding was equivocal. In situ hybridization for EBV-encoded RNA was positive in four of the five cases. Molecular studies by polymerase chain reaction (PCR) showed the presence of EBV in three of the five cases. PCR for detection of immunoglobulin heavy chain demonstrated identical monoclonal rearrangements in the original lymphoma and transformation in one case with available material. The CD4 lymphocyte count in each patient was less than 550/μL, indicating cellular dysfunction. Transformation of low-grade non-Hodgkin's lymphomas after fludarabine therapy might be associated with EBV and severe immunosuppression.

Authors
Shields, DJ; Byrd, JC; Abbondanzo, SL; Lichy, JH; Diehl, LF; Aguilera, NI
MLA Citation
Shields, DJ, Byrd, JC, Abbondanzo, SL, Lichy, JH, Diehl, LF, and Aguilera, NI. "Detection of Epstein-Barr virus in transformations of low-grade B-cell lymphomas after fludarabine treatment." Modern Pathology 10.11 (1997): 1151-1159.
PMID
9388067
Source
scival
Published In
Modern Pathology
Volume
10
Issue
11
Publish Date
1997
Start Page
1151
End Page
1159

Hemolytic anemia and cancer

Authors
Diehl, LF; Bolan, CD; Weiss, RB
MLA Citation
Diehl, LF, Bolan, CD, and Weiss, RB. "Hemolytic anemia and cancer." Cancer Treatment Reviews 22.1 (1996): 33-73.
PMID
8625331
Source
scival
Published In
Cancer Treatment Reviews
Volume
22
Issue
1
Publish Date
1996
Start Page
33
End Page
73
DOI
10.1016/S0305-7372(96)90015-8

Hypertensive reactions associated with paclitaxel

Authors
Jr, DAS; Phillips, ET; Weiss, RB; Dawson, NA; Diehl, LF; Rickles, NM
MLA Citation
Jr, DAS, Phillips, ET, Weiss, RB, Dawson, NA, Diehl, LF, and Rickles, NM. "Hypertensive reactions associated with paclitaxel." Cancer Investigation 14.4 (1996): 340-342.
PMID
8689429
Source
scival
Published In
Cancer Investigation (Informa)
Volume
14
Issue
4
Publish Date
1996
Start Page
340
End Page
342

Opportunistic pulmonary infections with fludarabine in previously treated patients with low-grade lymphoid malignancies: a role for Pneumocystis carinii pneumonia prophylaxis.

The high incidence of opportunistic pulmonary infections in fludarabine-treated patients at Walter Reed Army Medical Center (WRAMC) and in the literature are described. A CancerLit search of fludarabine from June 1983-April 1994 with subsequent cross referencing and a retrospective review of all patients receiving fludarabine at WRAMC was performed. A total of 2,269 patients with low-grade lymphoid malignancies who received 7,547 + cycles of fludarabine were identified from the literature. Seventy-three (3.2%) of these patients developed opportunistic infections. Seventy-one (97%) of these infections occurred in patients who were pretreated with alkylator regimens or corticosteroids. Forty-five (2%) of these were of respiratory origin and associated with a 56% mortality rate. In contrast, 6 of the 21 patients (29%) treated with fludarabine at WRAMC developed opportunistic pulmonary infections which included three Pneumocystis carinii (PCP), one PCP/disseminated Candidiasis, one Mycobacterium avium intracellulare, and one Aspergillus niger pneumonia. These infections developed during and after treatment with fludarabine in alkylator-resistant patients who had received corticosteroids before (n = 6), during (n = 1), or after (n = 4) fludarabine therapy. Lack of PCP prophylaxis was the only significant (P = .018) variable that differentiated patients who developed opportunistic pulmonary infections. Corticosteroid treatment before, during, or after fludarabine treatment in patients with alkylator-resistant, low-grade lymphoid malignancies who have not received PCP prophylaxis is associated with an increased risk of opportunistic pulmonary infections. Aggressive work-up of pulmonary syndromes and PCP prophylaxis in these patients should be considered during and after treatment with fludarabine.

Authors
Byrd, JC; Hargis, JB; Kester, KE; Hospenthal, DR; Knutson, SW; Diehl, LF
MLA Citation
Byrd, JC, Hargis, JB, Kester, KE, Hospenthal, DR, Knutson, SW, and Diehl, LF. "Opportunistic pulmonary infections with fludarabine in previously treated patients with low-grade lymphoid malignancies: a role for Pneumocystis carinii pneumonia prophylaxis." American journal of hematology 49.2 (June 1995): 135-142.
PMID
7771465
Source
epmc
Published In
American Journal of Hematology
Volume
49
Issue
2
Publish Date
1995
Start Page
135
End Page
142
DOI
10.1002/ajh.2830490207

Fatal recurrence of autoimmune hemolytic anemia following pentostatin therapy in a patient with a history of fludarabine-associated hemolytic anemia

Authors
Byrd, JC; Hertler, AA; Weiss, RB; Freiman, J; Kweder, SL; Diehl, LF
MLA Citation
Byrd, JC, Hertler, AA, Weiss, RB, Freiman, J, Kweder, SL, and Diehl, LF. "Fatal recurrence of autoimmune hemolytic anemia following pentostatin therapy in a patient with a history of fludarabine-associated hemolytic anemia." Annals of Oncology 6.3 (1995): 300-301.
PMID
7612497
Source
scival
Published In
Annals of Oncology
Volume
6
Issue
3
Publish Date
1995
Start Page
300
End Page
301

Equilibration of hemoglobin concentration after transfusion in medical inpatients not actively bleeding

Authors
Wiesen, AR; Hospenthal, DR; Byrd, JC; Glass, KL; Howard, RS; Diehl, LF
MLA Citation
Wiesen, AR, Hospenthal, DR, Byrd, JC, Glass, KL, Howard, RS, and Diehl, LF. "Equilibration of hemoglobin concentration after transfusion in medical inpatients not actively bleeding." Annals of Internal Medicine 121.4 (1994): 278-280.
PMID
8037410
Source
scival
Published In
Annals of Internal Medicine
Volume
121
Issue
4
Publish Date
1994
Start Page
278
End Page
280

Mean platelet volume improves upon the megathrombocyte index but cannot replace the blood film examination in the evaluation of thrombocytopenia

The measurement of the number of platelets larger than 3 microns (megathrombocyte index) is the first element in the evaluation of thrombocytopenia. This is currently performed by counting the number of large platelets on the peripheral blood film. The MPV (mean platelet volume) is an automated measurement of the platelet volume. This study examines the mean values, correlations, sensitivity, specificity and the receiver operating characteristic curve (comparison of two tests) to determine which of these tests better separates the production state. For increased vs. decreased production, the MPV was 10.0 + 1.9 fL and 8.0 + 1.5 fL (P < .0001) respectively and the megathrombocyte index (MEGA) was 19.0 + 17.6% and 11.5 + 14.9% (P < .007) respectively. The correlation with the state of production was better for MPV (R = .47) than for MEGA (R = .20). For the MPV a sensitivity of 80% occurred with the MPV ≥ 8.4 fL with a specificity of 71%. For a MEGA ≥ 6%, the sensitivity was 80% but the specificity was 43%. For any MPV the sensitivity and specificity were better than for any MEGA. The Receiver Operating Characteristic Curve demonstrated that the MPV is a better test than the MEGA for separating the production into increased and decreased states. The MPV is a better test than the MEGA and will add to, but not replace, examination of the peripheral blood film in the diagnosis of thrombocytopenia.

Authors
Vukelja, SJ; Krishnan, J; Diehl, LF
MLA Citation
Vukelja, SJ, Krishnan, J, and Diehl, LF. "Mean platelet volume improves upon the megathrombocyte index but cannot replace the blood film examination in the evaluation of thrombocytopenia." American Journal of Hematology 44.2 (1993): 89-94.
PMID
8266925
Source
scival
Published In
American Journal of Hematology
Volume
44
Issue
2
Publish Date
1993
Start Page
89
End Page
94

Congenital Neutropenia: How Low?-Reply

Authors
Diehl, LF
MLA Citation
Diehl, LF. "Congenital Neutropenia: How Low?-Reply." Archives of Internal Medicine 152.6 (June 1, 1992): 1329-1329.
Source
crossref
Published In
Archives of internal medicine
Volume
152
Issue
6
Publish Date
1992
Start Page
1329
End Page
1329
DOI
10.1001/archinte.1992.00400180165030

Congenital neutropenia: How low? [1]

Authors
Tomases, A; Reed, WW; Diehl, LF; Bessman, D
MLA Citation
Tomases, A, Reed, WW, Diehl, LF, and Bessman, D. "Congenital neutropenia: How low? [1]." Archives of Internal Medicine 152.6 (1992): 1329--.
Source
scival
Published In
Archives of Internal Medicine
Volume
152
Issue
6
Publish Date
1992
Start Page
1329-

Leukopenia, neutropenia, and reduced hemoglobin levels in healthy American blacks.

Hematologic profiles of 462 persons, mostly active-duty service members, were studied to determine whether hematologic differences between blacks and whites exist in a healthy population. Whites had significantly greater mean concentrations of leukocytes (6.73 vs 5.95 x 10(9)/L), neutrophils (3.96 vs 3.16 x 10(9)/L), and hemoglobin (153 vs 135 g/L for men, 147 vs 125 g/L for women). The mean differences were largely due to relatively symmetric shifts in the frequency distributions for these cell concentrations. No significant correlation was found between neutrophil count and morbidity from infection as measured by a standardized questionnaire. The use of separate hematologic reference values for blacks and whites should be considered.

Authors
Reed, WW; Diehl, LF
MLA Citation
Reed, WW, and Diehl, LF. "Leukopenia, neutropenia, and reduced hemoglobin levels in healthy American blacks." Archives of internal medicine 151.3 (March 1991): 501-505.
PMID
2001132
Source
epmc
Published In
Archives of internal medicine
Volume
151
Issue
3
Publish Date
1991
Start Page
501
End Page
505
DOI
10.1001/archinte.151.3.501

Leukopenia, neutropenia, and reduced hemoglobin levels in healthy american blacks

Hematologic profiles of 462 persons, mostly active-duty service members, were studied to determine whether hematologic differences between blacks and whites exist in a healthy population. Whites had significantly greater mean concentrations of leukocytes (6.73 vs 5.95×109/L), neutrophils (3.96 vs 3.16 × 109/L), and hemoglobin (153 vs 135 g/L for men, 147 vs 125 g/L for women). The mean differences were largely due to relatively symmetric shifts in the frequency distributions for these cell concentrations. No significant correlation was found between neutrophil count and morbidity from infection as measured by a standardized questionnaire. The use of separate hematologic reference values for blacks and whites should be considered.

Authors
Reed, WW; Diehl, LF
MLA Citation
Reed, WW, and Diehl, LF. "Leukopenia, neutropenia, and reduced hemoglobin levels in healthy american blacks." Archives of Internal Medicine 151.3 (1991): 501-505.
Source
scival
Published In
Archives of Internal Medicine
Volume
151
Issue
3
Publish Date
1991
Start Page
501
End Page
505
DOI
10.1001/archinte.151.3.501

The pattern of intrathoracic hodgkin's disease assessed by computed tomography

Computed tomography (CT) was used to define the sites of intrathoracic abnormality in Hodgkin's disease, determine a pattern of progression of disease in the thorax, and establish the place of this pattern of spread in the differential diagnosis of thoracic abnormalities. One hundred eight patients with newly diagnosed Hodgkin's disease were studied by chest CT. Seventy-seven patients had intrathoracic abnormalities. The pattern seen was one of contiguous spread from the anterior mediastinal/paratracheal area to the other mediastinal lymph node groups (aortopulmonary, subcarinal, posterior mediastinal, and internal mammary), to the hila, and then into the lung by extension or as discrete nodules. Involvement of the pleura, pericardium, or chest wall occurred only after the anterior mediastinal/paratracheal mass had enlarged to greater than 30% of the thoracic diameter. The probability that this pattern of contiguous lymph node spread occurred by chance alone was very small. Hodgkin's disease spreads from the anterior mediastinal/paratracheal area in a contiguous manner. Exceptions are unusual enough that when they occur, diagnoses other than Hodgkin's disease are more likely.

Authors
Diehl, LF; Hopper, KD; Giguere, J; Granger, E; Lesar, M
MLA Citation
Diehl, LF, Hopper, KD, Giguere, J, Granger, E, and Lesar, M. "The pattern of intrathoracic hodgkin's disease assessed by computed tomography." Journal of Clinical Oncology 9.3 (1991): 438-443.
PMID
1999713
Source
scival
Published In
Journal of Clinical Oncology
Volume
9
Issue
3
Publish Date
1991
Start Page
438
End Page
443

Radiation and chemotherapy in the treatment of esophageal cancer

Primary therapy for esophageal carcinoma is surgery or radiotherapy; however, the long-term prognosis is poor. Newer methods of adding combination chemotherapy to radiation therapy or surgery show potential to sterilize regional areas and improve the long-term survival.

Authors
Diehl, LF
MLA Citation
Diehl, LF. "Radiation and chemotherapy in the treatment of esophageal cancer." Gastroenterology Clinics of North America 20.4 (1991): 765-774.
PMID
1787012
Source
scival
Published In
Gastroenterology Clinics of North America
Volume
20
Issue
4
Publish Date
1991
Start Page
765
End Page
774

Mediastinal bulk in Hodgkin disease: Method of measurement versus prognosis

The presence of a large mediastinal mass (bulk disease) in patients with newly diagnosed Hodgkin disease is believed by many to predict a poorer prognosis and to warrant more aggressive treatment. These masses are formed by an aggregate of mediastinal lymph nodes. The determination of bulk disease is confusing, with at least 27 definitions having been proposed. This study seeks to determine the best definition, and determine the role of thoracic computed tomography (CT) versus chest radiographs in the evaluation of mediastinal bulk disease. One hundred seven consecutive newly diagnosed adult patients with Hodgkin disease were evaluated using 13 commonly used definitions of mediastinal bulk. Of the 76 patients with mediastinal disease, 73 had bulk disease as defined by at least one definition. Of the 16 patients who had recurrence of mediastinal disease, only the presence of bulk disease according to one definition (hilar adenopathy, ≥2 cm) was statistically significant in its prediction (P = .05). No definition based on the size of the mediastinal nodal mass reliably predicted those patients with recurrence. No differences in our data were found for differing stages or disease cell types, the presence of extension, or with differing treatment regimens. This study highlights the confusion and controversy surrounding the use of bulk disease of the mediastinum as an adverse prognostic indicator. The numerous methods of measuring mediastinal bulk in patients with newly diagnosed Hodgkin disease are confusing, overlap, and are not statistically reliable in predicting recurrence. Efforts to create a standard or ideal definition were unsuccessful. Thoracic CT was useful in those patients whose bulk disease distorted only one side of the mediastinal silhouette on chest radiographs.

Authors
Hopper, KD; Diehl, LF; Lynch, JC; McCauslin, MA
MLA Citation
Hopper, KD, Diehl, LF, Lynch, JC, and McCauslin, MA. "Mediastinal bulk in Hodgkin disease: Method of measurement versus prognosis." Investigative Radiology 26.12 (1991): 1101-1110.
PMID
1765446
Source
scival
Published In
Investigative Radiology
Volume
26
Issue
12
Publish Date
1991
Start Page
1101
End Page
1110

The significance of necrotic mediastinal lymph nodes on CT in patients with newly diagnosed Hodgkin disease

Necrosis in lymph nodes shown on CT in many patients with nodal metastases may indicate that the primary tumor is aggressive and has a high degree of malignancy. However, the significance of nodal necrosis in patients with mediastinal Hodgkin disease remains uncertain. We studied the thoracic CT scans of 76 patients who had newly diagnosed Hodgkin disease with mediastinal involvement with respect to the presence of necrosis (low attenuation, complex, fluidlike areas), the size and volume of the mass, the sites involved, extension ('E' disease), and the patients' clinical response to treatment. CT scans showed necrotic nodes in 16 patients (21%). The difference between these patients and those without necrotic nodes was not statistically significant with respect to sex, age, stage, distribution of disease, presence of E disease, cell type, mass diameter, or the presence of bulk disease (mass diameter/maximal thoracic diameter ≥0.33). The mass volume as measured by CT was not significantly (p=.08) larger (1274 cm3) than the group without necrotic nodes (876 cm3). An analysis of the various mediastinal sites involved showed no difference between patients with and without necrotic nodes. Lastly, the presence of necrotic nodes had no significant impact on patients' clinical response to treatment or survival. The presence of mediastinal necrotic nodes appears to have little radiologic or prognostic significance in patients with newly diagnosed Hodgkin disease.

Authors
Hopper, KD; Diehl, LF; Cole, BA; Lynch, JC; Meilstrup, JW; McCauslin, MA
MLA Citation
Hopper, KD, Diehl, LF, Cole, BA, Lynch, JC, Meilstrup, JW, and McCauslin, MA. "The significance of necrotic mediastinal lymph nodes on CT in patients with newly diagnosed Hodgkin disease." American Journal of Roentgenology 155.2 (1990): 267-270.
PMID
2115249
Source
scival
Published In
American Journal of Roentgenology
Volume
155
Issue
2
Publish Date
1990
Start Page
267
End Page
270

Enlargement of mediastinal masses on simulation films: A radiotherapeutic problem in the management of patients with Hodgkin's disease

The size of the mediastinal mass on standard posterior-anterior chest radiograph in stage I and stage II Hodgkin's disease has both prognostic and therapeutic importance. But the actual treatment is based on the anterior-posterior supine simulation film. Problems arise when the prognosis (whether all the disease can be effectively contained in an irradiation port) and toxicity (more lung and heart irradiated or chemotherapy required) are changed when the mass is markedly enlarged on the radiation simulation film. We report two patients with small mediastinal masses on standard posterior-anterior chest radiographs that appeared to enlarge markedly on radiation simulation films. Differences in the direction of the X-ray beam, distance from the subject, and patient position are shown to increase artificially the size of a mediastinal mass on simulation films. The staging and therapeutic implications are discussed.

Authors
Vukelja, SJ; Andejeski, Y; Giguere, JK; Yuen, A; Diehl, LF
MLA Citation
Vukelja, SJ, Andejeski, Y, Giguere, JK, Yuen, A, and Diehl, LF. "Enlargement of mediastinal masses on simulation films: A radiotherapeutic problem in the management of patients with Hodgkin's disease." Medical and Pediatric Oncology 18.1 (1990): 44-48.
PMID
2294391
Source
scival
Published In
Pediatric Blood and Cancer
Volume
18
Issue
1
Publish Date
1990
Start Page
44
End Page
48
DOI
10.1002/mpo.2950180109

Induction chemotherapy in Jehovah's Witnesses with leukaemia

Authors
Hargis, JB; Waddell, DJ; Diehl, L; Redmond, J
MLA Citation
Hargis, JB, Waddell, DJ, Diehl, L, and Redmond, J. "Induction chemotherapy in Jehovah's Witnesses with leukaemia." Lancet 336.8714 (1990): 563-564.
PMID
1975054
Source
scival
Published In
Lancet
Volume
336
Issue
8714
Publish Date
1990
Start Page
563
End Page
564

RE: Hodgkin disease Clinical utility of CT in initial staging and treatment

Authors
Hopper, KD; Diehl, LF
MLA Citation
Hopper, KD, and Diehl, LF. "RE: Hodgkin disease Clinical utility of CT in initial staging and treatment." Investigative Radiology 24.10 (January 1, 1989): 823-. (Letter)
Source
scopus
Published In
Investigative Radiology
Volume
24
Issue
10
Publish Date
1989
Start Page
823

Trephine needle bone marrow biopsy in the initial staging of Hodgkin disease: Sensitivity and specificity of the Ann Arbor staging procedure criteria

The purpose of this study was to test the value of the Ann Arbor staging procedures committee criteria in defining a group of newly diagnosed patients with Hodgkin disease who do not have involvement of the bone marrow and do not need this procedure performed. One hundred sixty-six bilateral and 16 unilateral trephine bone marrow biopsies were performed in a consecutive series of 182 patients undergoing initial staging for Hodgkin disease. Bone marrow involvement was found in 13 patients. Advanced stage, defined as stage III or IV, occurring in 92%, anemia occurring in 100%, and 'B' symptoms present in 100% were found to be the most sensitive indicators for bone marrow involvement. Osseous disease (99%), platelet count < 150,000/mm3 (98%), and WBC < 4,800/mm3 (94%) were the most specific parameters. The known association of bone marrow involvement with older patients, lymphocyte depleted histology, lower blood cell counts, anemia, advanced stage, and poorer survival is verified. The Ann Arbor staging procedures committee criteria for performing a bone marrow biopsy were shown to be 100% sensitive and 40% specific. Use of these criteria would have found all 13 patients with bone marrow involvement. Of the 73 patients who did not meet the criteria, no patient had bone marrow involvement. Use of the Ann Arbor staging procedures committee criteria is recommended.

Authors
Ellis, ME; Diehl, LF; Granger, E; Elson, E
MLA Citation
Ellis, ME, Diehl, LF, Granger, E, and Elson, E. "Trephine needle bone marrow biopsy in the initial staging of Hodgkin disease: Sensitivity and specificity of the Ann Arbor staging procedure criteria." American Journal of Hematology 30.3 (1989): 115-120.
PMID
2644822
Source
scival
Published In
American Journal of Hematology
Volume
30
Issue
3
Publish Date
1989
Start Page
115
End Page
120

Does review of peripheral blood smears help in the initial workup of common anemias?

Sixty-five physicians were tested to determine the effect of their reviews of red blood cell morphology on their subsequent diagnoses of and workup plans for common anemias. The subjects read clinical and laboratory data for six pairs of cases of anemia, reviewing the blood smear for one case in each pair. They correctly identified the presence or absence of morphologic features on the blood smears 82% of the time. In spite of excellent morphologic discrimination, the number of tests ordered was not affected by blood smear review. In fact, the quality of the physicians' workup plans, measured by numbers of tests appropriately ordered and excluded, was slightly but significantly better when they did not review the smears (p<0.005). In addition, smear review did not significantly improve diagnostic accuracy for any of the common anemias studied. Significantly more correct diagnoses were made without smear review for vitamin B 12-folate deficiency anemia (p<0.015) and thalassemia (p<0.0001). Although routine review of blood smears by physicians in the management of common anemias may provide useful information, the authors were unable to demonstrate an improvement in the number or appropriateness of tests ordered or diagnostic accuracy in spite of excellent morphologic discrimination. © 1989 Society of General Internal Medicine.

Authors
Simmons, JO; Noel, GL; Diehl, LF
MLA Citation
Simmons, JO, Noel, GL, and Diehl, LF. "Does review of peripheral blood smears help in the initial workup of common anemias?." Journal of General Internal Medicine 4.6 (1989): 473-481.
PMID
2585155
Source
scival
Published In
Journal of General Internal Medicine
Volume
4
Issue
6
Publish Date
1989
Start Page
473
End Page
481
DOI
10.1007/BF02599543

Hematologic indexes in men attending an infertility clinic.

To assess whether oligospermia in infertile men might be associated with abnormalities of another rapidly dividing cell population, namely, blood cells, we studied retrospectively hematologic indexes in 72 unselected men initially attending an infertility clinic and 119 healthy controls. Red cell and platelet parameters were similar in the two groups. The infertility clinic patients had significantly reduced total leukocyte counts (5818 +/- 179 versus 6397 +/- 174 per mm3; p less than 0.05). This leukopenia reflected a reduction in lymphocyte count (1697 +/- 69 versus 2206 +/- 80 per mm3; p less than 0.0001) but not in neutrophil count (3331 +/- 144 versus 3678 +/- 139 per mm3; p = NS). Lymphopenia was not correlated with sperm density. A prospective study of 24 fertile controls and 12 infertile, oligospermic men revealed no differences between these groups in numbers of lymphocytes, T lymphocytes, T4 (helper) lymphocytes, or T8 (suppressor) lymphocytes. In conclusion, lymphopenia noted retrospectively in men attending an infertile clinic was unrelated to sperm density and was not confirmed in a prospective study. Combined with normal red cell and platelet parameters these findings suggest that hematologic indexes are probably normal in infertile men.

Authors
Glass, AR; Reed, W; Diehl, L
MLA Citation
Glass, AR, Reed, W, and Diehl, L. "Hematologic indexes in men attending an infertility clinic." Archives of andrology 20.2 (January 1988): 177-180.
PMID
3395162
Source
epmc
Published In
Archives of Andrology
Volume
20
Issue
2
Publish Date
1988
Start Page
177
End Page
180
DOI
10.3109/01485018808987071

Fatal esorubicin-induced cardiomyopathy: report of a case and review of the literature

A case of fatal dilated cardiomyopathy induced by esorubicin (ESO) at a total dose of 740 mg/m2, given in 27 doses over 650 days, is reported. The sudden onset, rapid clinical deterioration, and fatal outcome are detailed. The outcome was not predicted by serial rest ejection fractions or clinical signs. The data from animal studies, phase 1 and phase 2 clinical testing, are reviewed, demonstrating the almost complete absence of reports of ESO-induced cardiotoxicity. Studies reviewing ejection fractions and myocardial biopsy scores show that ESO can be cardiotoxic and may produce fatal dilated cardiomyopathy. © 1988 Springer-Verlag.

Authors
Diehl, LF; Banks, A; Carter, W; Klein, MA; Muss, HB; Weiss, RB
MLA Citation
Diehl, LF, Banks, A, Carter, W, Klein, MA, Muss, HB, and Weiss, RB. "Fatal esorubicin-induced cardiomyopathy: report of a case and review of the literature." Cancer Chemotherapy and Pharmacology 21.4 (1988): 347-350.
PMID
3286024
Source
scival
Published In
Cancer Chemotherapy and Pharmacology
Volume
21
Issue
4
Publish Date
1988
Start Page
347
End Page
350
DOI
10.1007/BF00264203

Hematologic indexes in men attending an infertility clinic

To assess whether oligospermia in infertile men might be associated with abnormalities of another rapidly dividing cell population, namely, blood cells, we studied retrospectively hematologic indexes in 72 unselected men initially attending an infertility clinic and 119 healthy controls. Red cell and platelet parameters were similar in the two groups. The infertility clinic patients had significantly reduced total leukocyte counts (5818 ± 179 versus 6397 ± 174 per mm3; p < 0.05). This leukopenia reflected a reduction in lymphocyte count (1697 ± 69 versus 2206 ± 80 per mm3; p < 0.0001) but not in neutrophil count (3331 ± 144 versus 3678 ± 139 per mm3; p = NS). Lymphopenia was not correlated with sperm density. A prospective study of 24 fertile controls and 12 infertile, oligospermic men revealed no differences between these goups in numbers of lymphocytes, T lymphocytes, T4 (helper) lymphocytes, or T8 (suppressor) lymphocytes. In conclusion, lymphopenia noted retrospectively in men attending an infertile clinic was unrelated to sperm density and was not confirmed in a prospective study. Combined with normal red cell and platelet parameters these findings suggest that hematologic indexes are probably normal in infertile men.

Authors
Glass, AR; Reed, W; Diehl, L
MLA Citation
Glass, AR, Reed, W, and Diehl, L. "Hematologic indexes in men attending an infertility clinic." Archives of Andrology 20.2 (1988): 177-180.
Source
scival
Published In
Archives of Andrology
Volume
20
Issue
2
Publish Date
1988
Start Page
177
End Page
180

Hodgkin disease: Clinical utility of CT in initial staging and treatment

One hundred seven consecutive new cases of Hodgkin disease were evaluated with chest radiography and computed tomography (CT) for initial staging. The data were evaluated with regard to five popular treatment protocols for Hodgkin disease. Thoracic CT scans were normal in 30 of 31 patients who had normal radiographs. In the remaining 76 patients, CT demonstrated 194 new sites of disease and disproved 25 suspected sites of disease. The use of CT scans changed the staging of disease in 20 patients, 16 of whom had extranodal extension. The effect of using CT findings on treatment depended on whether radiation therapy was used, and, if so, which treatment protocol was followed. The use of CT findings would have changed the treatment in 6.5%-62.7% of new cases of Hodgkin disease. The authors recommend that CT scans be obtained in all patients with Hodgkin disease, especially those with abnormal chest radiographs.

Authors
Hopper, KD; Diehl, LF; Lesar, M; Barnes, M; Granger, E; Baumann, J
MLA Citation
Hopper, KD, Diehl, LF, Lesar, M, Barnes, M, Granger, E, and Baumann, J. "Hodgkin disease: Clinical utility of CT in initial staging and treatment." Radiology 169.1 (1988): 17-22.
PMID
3420256
Source
scival
Published In
Radiology
Volume
169
Issue
1
Publish Date
1988
Start Page
17
End Page
22

A comparison of randomized concurrent control groups with matched historical control groups: Are historical controls valid?

The use of a historical control group is predicated on the assumption that survival and relapse-free survival in the historical control group closely approximate the survival and relapse-free survival in a randomized concurrent control group. This assumption has never been tested. This study compares survival and relapse-free survival in randomized control groups with historical control groups matched for disease, stage, and follow-up. Of the 43 matched control groups, 42% varied by more than 10 percentage points, 21% varied by more than 20 percentage points, and 5% varied by more than 30 percentage points. Of the 18 that varied by > 10 percentage points, 17 had superior survival or relapse-free survival in the randomized concurrent control group. This study indicates that the assumption that historical control groups may replace randomized concurrent control groups is not valid.

Authors
Diehl, LF; Perry, DJ
MLA Citation
Diehl, LF, and Perry, DJ. "A comparison of randomized concurrent control groups with matched historical control groups: Are historical controls valid?." Journal of Clinical Oncology 4.7 (1986): 1114-1120.
PMID
3723167
Source
scival
Published In
Journal of Clinical Oncology
Volume
4
Issue
7
Publish Date
1986
Start Page
1114
End Page
1120

Changes in criteria for tumor response.

Authors
Perry, DJ; Diehl, LF
MLA Citation
Perry, DJ, and Diehl, LF. "Changes in criteria for tumor response." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 3.2 (1985): 287--.
PMID
3968555
Source
scival
Published In
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume
3
Issue
2
Publish Date
1985
Start Page
287-

Ambulatory use of high-dose intravenous morphine for severe pain

A case is presented that describes the use of an intravenous morphine infusion to treat severe pain in an outpatient setting. The patient had severe pain secondary to tumor involvement of the brachial plexus. Morphine was administered as a concentrated solution (50 mg/ml), using an autosyringe (model As-2F) via a Hickman catheter. The dose was titrated to pain relief. A dose of 200-250 mg/h was required.

Authors
Adams, JD; Diehl, LF; Wilson, JP
MLA Citation
Adams, JD, Diehl, LF, and Wilson, JP. "Ambulatory use of high-dose intravenous morphine for severe pain." Drug Intelligence and Clinical Pharmacy 18.2 (1984): 138-140.
PMID
6697875
Source
scival
Published In
Drug Intelligence and Clinical Pharmacy
Volume
18
Issue
2
Publish Date
1984
Start Page
138
End Page
140

Skin metastases confined to a field of previous irradiation. Report of two cases and review of the literature

Two cases of tumor recurrence within a previously irradiated skin area are reported. Typical lesions evolve from an erythematous base and progress to induration and tumor papules. A review of clinical literature indicates that irradiation does not increase the frequency of metastases. Experimental data suggest that irradiation does increase metastases as a result of both local mechanical factors and increased tumor-cell survival.

Authors
Diehl, LF; Hurwitz, MA; Johnson, SA; Butler, WM; Taylor, HG
MLA Citation
Diehl, LF, Hurwitz, MA, Johnson, SA, Butler, WM, and Taylor, HG. "Skin metastases confined to a field of previous irradiation. Report of two cases and review of the literature." Cancer 53.9 (1984): 1864-1868.
PMID
6704918
Source
scival
Published In
Cancer
Volume
53
Issue
9
Publish Date
1984
Start Page
1864
End Page
1868

Radiation as salvage therapy for patients with Hodgkin's disease relapsing after MOPP (mechlorethamine, vincristine, prednisone, and procarbazine) chemotherapy

Six patients with Hodgkin's disease who failed MOPP (mechlorethamine, vincristine, prednisone, and procarbazine) chemotherapy, with recurrences confined to lymph node areas, are reported. All patients were treated with tumoricidal doses of irradiation in mantle, inverted Y, or whole-abdominal fields. All six patients achieved complete remission, with minimal toxicity. Disease-free survival ranged from 3 to 38 months, with four patients remaining in complete remission at 9, 15, 27, and 38 months. Radiation therapy should be considered in patients failing MOPP chemotherapy with lymph node disease.

Authors
Diehl, LF; Perry, DJ; Terebelo, H; Baldwin, PE; Hurwitz, M; Kimball, DB; Dorn, RV
MLA Citation
Diehl, LF, Perry, DJ, Terebelo, H, Baldwin, PE, Hurwitz, M, Kimball, DB, and Dorn, RV. "Radiation as salvage therapy for patients with Hodgkin's disease relapsing after MOPP (mechlorethamine, vincristine, prednisone, and procarbazine) chemotherapy." Cancer Treatment Reports 67.9 (1983): 827-829.
PMID
6883360
Source
scival
Published In
Cancer Treatment Reports
Volume
67
Issue
9
Publish Date
1983
Start Page
827
End Page
829

Study on the comparability of 6 versus 12 cycles of adjuvant cyclophosphamide, methotrexate, and fluorouracil.

Authors
Diehl, LF; Perry, DJ; Tang, DB
MLA Citation
Diehl, LF, Perry, DJ, and Tang, DB. "Study on the comparability of 6 versus 12 cycles of adjuvant cyclophosphamide, methotrexate, and fluorouracil." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 1.10 (1983): 663-664.
PMID
6689422
Source
scival
Published In
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume
1
Issue
10
Publish Date
1983
Start Page
663
End Page
664

Gamma (immune) interferon production by leukocytes from a patient with a TG cell proliferative disease.

We report a patient with a disease characterized by proliferation of T cells with Fc receptors for IgG (TG). However, unlike lymphoid cells from normal individuals or from patients with other lymphoid malignancies, the patient's lymphocytes spontaneously produced gamma interferon (IFN-gamma) in vitro. The peripheral lymphocytes consisted of 95% TG cells, which exhibited the morphological characteristics of T-cell chronic lymphocytic leukemia (CLL) and were normal on cytochemical and chromosome analysis. The majority of TG cells were OKT3+, OKT8+, and OKT4-, 3A1-. These cells failed to express suppressor cell activity and displayed depressed levels of natural killer activity, but mediated antibody-dependent cell-mediated cytotoxicity. The spontaneous production of IFN-gamma by human peripheral lymphoid cells as demonstrated in this study may serve as a probe for studying the relationship between IFN-gamma and the proliferation of human T-cell subsets.

Authors
Hooks, JJ; Haynes, BF; Detrick-Hooks, B; Diehl, LF; Gerrard, TL; Fauci, AS
MLA Citation
Hooks, JJ, Haynes, BF, Detrick-Hooks, B, Diehl, LF, Gerrard, TL, and Fauci, AS. "Gamma (immune) interferon production by leukocytes from a patient with a TG cell proliferative disease." Blood 59.1 (January 1982): 198-201.
PMID
6172170
Source
pubmed
Published In
Blood
Volume
59
Issue
1
Publish Date
1982
Start Page
198
End Page
201

Increased heat sensitivity of red blood cells in hereditary elliptocytosis with acquired cobalamin (vitamin B12) deficiency

Structural membrane proteins were studied from erythrocytes (RBC) of a patient with a nonhemolytic form of hereditary elliptocytosis (HE) who developed a microcytic anemia with fragmented RBC while cobalamin (B12) deficient. Evidence is presented for qualitative changes in the patient's RBC membranes not related to a loss of structural proteins. Sensitivity of RBC to heat treatment was studied as well as quantitative changes in proteins by densitometry of 1% SDS-10% PAGE gels. Fractions of RBC of various sizes from the patient while B12 deficient all possessed a marked degree of heat sensitivity when compared to RBC from the patient after B12 repletion, normal family members, HE controls, B12-deficient controls, anemic controls, and normal controls. Because loss of spectrin (bands 1 + 2) from heat-sensitive RBC membranes in hereditary pyropoikilocytosis has been reported, the amount of spectrin relative to band 3 was measured. No decrease in the ratio of bands (1 + 2)/3 was found. In addition, no chromatographically abnormal membrane proteins were found by SDS-PAGE of the patient's RBC while B12 deficient. Our findings indicate that B12 deficiency results in an abnormal membrane with enhanced instability in some forms of He. Since protein loss was not found, we conclude that an alteration in membrane protein interaction may be involved.

Authors
Schoomaker, EB; Butler, WM; Diehl, LF
MLA Citation
Schoomaker, EB, Butler, WM, and Diehl, LF. "Increased heat sensitivity of red blood cells in hereditary elliptocytosis with acquired cobalamin (vitamin B12) deficiency." Blood 59.6 (1982): 1213-1219.
PMID
7082825
Source
scival
Published In
Blood
Volume
59
Issue
6
Publish Date
1982
Start Page
1213
End Page
1219

Metastatic thymoma with myasthenia gravis. Complete remission with combination chemotherapy

A 29-year-old male developed myasthenia gravis 29 months after resection of a 'benign' mediastinal thymoma. Metastatic thymoma was found in the pleura 45 months after the initial surgical resection. Combination chemotherapy with cyclophosphamide and doxorubicin produced a complete remission of the metastatic thymoma which has continued for 13 months. Concurrently, there has been a marked increase in neuromuscular function.

Authors
Butler, WM; Diehl, LF; Taylor, HG; Weltz, MD
MLA Citation
Butler, WM, Diehl, LF, Taylor, HG, and Weltz, MD. "Metastatic thymoma with myasthenia gravis. Complete remission with combination chemotherapy." Cancer 50.3 (1982): 419-422.
PMID
7093885
Source
scival
Published In
Cancer
Volume
50
Issue
3
Publish Date
1982
Start Page
419
End Page
422

Radiation as salvage therapy for patients with Hodgkin's disease (HD) relapsing after MOPP chemotherapy

Authors
Diehl, L; Perry, D; Terebelo, H
MLA Citation
Diehl, L, Perry, D, and Terebelo, H. "Radiation as salvage therapy for patients with Hodgkin's disease (HD) relapsing after MOPP chemotherapy." Proceedings of the American Society of Clinical Oncology Vol. 1 (1982): C-612.
Source
scival
Published In
Proceedings of the American Society of Clinical Oncology
Volume
Vol. 1
Publish Date
1982
Start Page
C
End Page
612

Lhermitte's sign in cobalamin (vitamin B12) deficiency.

Authors
Butler, WM; Taylor, HG; Diehl, LF
MLA Citation
Butler, WM, Taylor, HG, and Diehl, LF. "Lhermitte's sign in cobalamin (vitamin B12) deficiency." JAMA 245.10 (March 1981): 1059-.
PMID
7463627
Source
epmc
Published In
JAMA : the journal of the American Medical Association
Volume
245
Issue
10
Publish Date
1981
Start Page
1059
DOI
10.1001/jama.1981.03310350047024

Gamma (immune) interferon produced by leukocytes from a patients with a T cell proliferation disease.

Authors
Hooks, JJ; Haynes, BF; Detrick-Hooks, B; Diehl, LF; Gerrard, TL; Fauci, AS
MLA Citation
Hooks, JJ, Haynes, BF, Detrick-Hooks, B, Diehl, LF, Gerrard, TL, and Fauci, AS. "Gamma (immune) interferon produced by leukocytes from a patients with a T cell proliferation disease." Trans Assoc Am Physicians 94 (1981): 198-203.
PMID
6178202
Source
pubmed
Published In
Transactions of the Association of American Physicians
Volume
94
Publish Date
1981
Start Page
198
End Page
203

Lhermitte's sign in cobalamin (vitamin B12) deficiency

Lhermitte's sign (electric shocklike dysesthesia produced by neck flexion) was first described by Marie and Chatelin in 1917. In 1924, Lhermitte et al described in detail a patient with multiple sclerosis and electric dysesthesias. Since then, Lhermitte's sign has been described in association with tumors of the cervical cord, arachnoiditis, cervical spondylitis, radiation myelitis, subacute combined degeneration of the cord, and nitrous oxide exposure. Recently, we have seen two patients with Lhermitte's sign who were found to have cobalamin (vitamin B12) deficiency.

Authors
Butler, WM; Taylor, HG; Diehl, LF
MLA Citation
Butler, WM, Taylor, HG, and Diehl, LF. "Lhermitte's sign in cobalamin (vitamin B12) deficiency." Journal of the American Medical Association 245.10 (1981): 1059--.
Source
scival
Published In
Journal of the American Medical Association
Volume
245
Issue
10
Publish Date
1981
Start Page
1059-
DOI
10.1001/jama.245.10.1059
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