You are here

Beaven, Anne Wood

Overview:

My particular area of research interest is clinical trails for patients with lymphoma.

Positions:

Associate Professor of Medicine

Medicine, Hematological Malignancies
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2000

M.D. — University of North Carolina at Chapel Hill

Grants:

SGN CD19A-004 Large B Cell Lymphoma DLBCL

Administered By
Duke Cancer Institute
AwardedBy
Seattle Genetics, Inc
Role
Principal Investigator
Start Date
February 08, 2017
End Date
February 28, 2022

MEDI D4190C00023

Administered By
Duke Cancer Institute
AwardedBy
MedImmune, Inc.
Role
Principal Investigator
Start Date
October 01, 2016
End Date
September 30, 2021

A Phase 2 Multicenter Study Evaluationg the Efficacy of KTE-C19 in Subjects with Relapsed/Refracory MCL

Administered By
Duke Cancer Institute
AwardedBy
Kite Pharma, Inc.
Role
Principal Investigator
Start Date
September 25, 2016
End Date
September 24, 2021

A Randomized Open Label Phase 2 Study of Denintuzumab mafodotin (SGN -CD19A)

Administered By
Duke Cancer Institute
AwardedBy
Seattle Genetics, Inc
Role
Principal Investigator
Start Date
May 23, 2016
End Date
May 22, 2021

A Phase 1/2 Study Evaluating Brentuximab vedotin in combination with nivolumab in patients with relapsed or refractory Hodgkin lymphoma

Administered By
Duke Cancer Institute
AwardedBy
Seattle Genetics, Inc
Role
Principal Investigator
Start Date
February 22, 2016
End Date
February 21, 2021

PNT2258-03-DLBCL - Wolverine

Administered By
Duke Cancer Institute
AwardedBy
ProNAi Therapeutics, Inc.
Role
Principal Investigator
Start Date
September 05, 2015
End Date
September 04, 2020

Phase 3 Randomized CC-5013-DLC-002

Administered By
Duke Cancer Institute
AwardedBy
Celgene Corporation
Role
Principal Investigator
Start Date
April 02, 2015
End Date
April 01, 2020

PCI 32765 MCL 3002

Administered By
Duke Cancer Institute
AwardedBy
Janssen Research & Development, LLC
Role
Principal Investigator
Start Date
November 29, 2013
End Date
November 28, 2019

Phase 2 Nivolumab for R/R Follicular Lymphoma (CA 209-140-0011)

Administered By
Duke Cancer Institute
AwardedBy
The Bristol-Myers/Sanofi Pharmaceuticals, Inc. Partnership
Role
Principal Investigator
Start Date
May 01, 2014
End Date
April 30, 2019

A Phase II study of the ALK inhibitor, Ceritinib (LDK378), in relapsed/refractory ALK + Hematologic Malignancies

Administered By
Duke Cancer Institute
AwardedBy
Novartis Pharmaceuticals Corporation
Role
Principal Investigator
Start Date
April 04, 2015
End Date
August 31, 2018

A Phase I Dose Escalation Study of OMP-52M51 in Subjects with Lymphoid malignancies

Administered By
Duke Cancer Institute
AwardedBy
OncoMed Pharmaceuticals
Role
Principal Investigator
Start Date
February 02, 2014
End Date
February 01, 2017
Show More

Publications:

The Genetic Basis of Hepatosplenic T-cell Lymphoma.

Hepatosplenic T-cell lymphoma (HSTL) is a rare and lethal lymphoma; the genetic drivers of this disease are unknown. Through whole-exome sequencing of 68 HSTLs, we define recurrently mutated driver genes and copy-number alterations in the disease. Chromatin-modifying genes, including SETD2, INO80, and ARID1B, were commonly mutated in HSTL, affecting 62% of cases. HSTLs manifest frequent mutations in STAT5B (31%), STAT3 (9%), and PIK3CD (9%), for which there currently exist potential targeted therapies. In addition, we noted less frequent events in EZH2, KRAS, and TP53SETD2 was the most frequently silenced gene in HSTL. We experimentally demonstrated that SETD2 acts as a tumor suppressor gene. In addition, we found that mutations in STAT5B and PIK3CD activate critical signaling pathways important to cell survival in HSTL. Our work thus defines the genetic landscape of HSTL and implicates gene mutations linked to HSTL pathogenesis and potential treatment targets.Significance: We report the first systematic application of whole-exome sequencing to define the genetic basis of HSTL, a rare but lethal disease. Our work defines SETD2 as a tumor suppressor gene in HSTL and implicates genes including INO80 and PIK3CD in the disease. Cancer Discov; 7(4); 369-79. ©2017 AACR.See related commentary by Yoshida and Weinstock, p. 352This article is highlighted in the In This Issue feature, p. 339.

Authors
McKinney, M; Moffitt, AB; Gaulard, P; Travert, M; De Leval, L; Nicolae, A; Raffeld, M; Jaffe, ES; Pittaluga, S; Xi, L; Heavican, T; Iqbal, J; Belhadj, K; Delfau-Larue, MH; Fataccioli, V; Czader, MB; Lossos, IS; Chapman-Fredricks, JR; Richards, KL; Fedoriw, Y; Ondrejka, SL; Hsi, ED; Low, L; Weisenburger, D; Chan, WC; Mehta-Shah, N; Horwitz, S; Bernal-Mizrachi, L; Flowers, CR; Beaven, AW; Parihar, M; Baseggio, L; Parrens, M; Moreau, A; Sujobert, P; Pilichowska, M; Evens, AM; Chadburn, A et al.
MLA Citation
McKinney, M, Moffitt, AB, Gaulard, P, Travert, M, De Leval, L, Nicolae, A, Raffeld, M, Jaffe, ES, Pittaluga, S, Xi, L, Heavican, T, Iqbal, J, Belhadj, K, Delfau-Larue, MH, Fataccioli, V, Czader, MB, Lossos, IS, Chapman-Fredricks, JR, Richards, KL, Fedoriw, Y, Ondrejka, SL, Hsi, ED, Low, L, Weisenburger, D, Chan, WC, Mehta-Shah, N, Horwitz, S, Bernal-Mizrachi, L, Flowers, CR, Beaven, AW, Parihar, M, Baseggio, L, Parrens, M, Moreau, A, Sujobert, P, Pilichowska, M, Evens, AM, and Chadburn, A et al. "The Genetic Basis of Hepatosplenic T-cell Lymphoma." Cancer discovery 7.4 (April 2017): 369-379.
PMID
28122867
Source
epmc
Published In
Cancer Discovery
Volume
7
Issue
4
Publish Date
2017
Start Page
369
End Page
379
DOI
10.1158/2159-8290.cd-16-0330

Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study.

Selective BCL2 inhibition with venetoclax has substantial activity in patients with relapsed or refractory chronic lymphocytic leukaemia. Combination therapy with rituximab enhanced activity in preclinical models. The aim of this study was to assess the safety, pharmacokinetics, and activity of venetoclax in combination with rituximab.Adult patients with relapsed or refractory chronic lymphocytic leukaemia (according to the 2008 Modified International Workshop on CLL guidelines) or small lymphocytic lymphoma were eligible for this phase 1b, dose-escalation trial. The primary outcomes were to assess the safety profile, to determine the maximum tolerated dose, and to establish the recommended phase 2 dose of venetoclax when given in combination with rituximab. Secondary outcomes were to assess the pharmacokinetic profile and analyse efficacy, including overall response, duration of response, and time to tumour progression. Minimal residual disease was a protocol-specified exploratory objective. Central review of the endpoints was not done. Venetoclax was dosed daily using a stepwise escalation to target doses (200-600 mg) and then monthly rituximab commenced (375 mg/m2 in month 1 and 500 mg/m2 in months 2-6). Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for adverse events version 4.0. Protocol-guided drug cessation was allowed for patients who achieved complete response (including complete response with incomplete marrow recovery) or negative bone marrow minimal residual disease. Analyses were done per protocol for all patients who commenced drug and included all patients who received at least one dose of venetoclax. Data were pooled across dose cohorts. Patients are still receiving therapy and follow-up is ongoing. The trial is registered at ClinicalTrials.gov, number NCT01682616.Between Aug 6, 2012, and May 28, 2014, we enrolled 49 patients. Common grade 1-2 toxicities included upper respiratory tract infections (in 28 [57%] of 49 patients), diarrhoea (27 [55%]), and nausea (25 [51%]). Grade 3-4 adverse events occurred in 37 (76%) of 49 patients; most common were neutropenia (26 [53%]), thrombocytopenia (eight [16%]), anaemia (seven [14%]), febrile neutropenia (six [12%]), and leucopenia (six [12%]). The most common serious adverse events were pyrexia (six [12%]), febrile neutropenia (five [10%]), lower respiratory tract infection, and pneumonia (each three [6%]). Clinical tumour lysis syndrome occurred in two patients (resulting in one death) who initiated venetoclax at 50 mg. After enhancing tumour lysis syndrome prophylaxis measures and commencing venetoclax at 20 mg, clinical tumour lysis syndrome did not occur. The maximum tolerated dose was not identified; the recommended phase 2 dose of venetoclax in combination with rituximab was 400 mg. Overall, 42 (86%) of 49 patients achieved a response, including a complete response in 25 (51%) of 49 patients. 2 year estimates for progression-free survival and ongoing response were 82% (95% CI 66-91) and 89% (95% CI 72-96), respectively. Negative marrow minimal residual disease was attained in 20 (80%) of 25 complete responders and 28 (57%) of 49 patients overall. 13 responders ceased all therapy; among these all 11 minimal residual disease-negative responders remain progression-free off therapy. Two with minimal residual disease-positive complete response progressed after 24 months off therapy and re-attained response after re-initiation of venetoclax.A substantial proportion of patients achieved an overall response with the combination of venetoclax and rituximab including 25 (51%) of 49 patients who achieved a complete response and 28 (57%) of 49 patients who achieved negative marrow minimal residual disease with acceptable safety. The depth and durability of responses observed with the combination offers an attractive potential treatment option for patients with relapsed or refractory chronic lymphocytic leukaemia and could allow some patients to maintain response after discontinuing therapy, a strategy that warrants further investigation in randomised studies.AbbVie Inc and Genentech Inc.

Authors
Seymour, JF; Ma, S; Brander, DM; Choi, MY; Barrientos, J; Davids, MS; Anderson, MA; Beaven, AW; Rosen, ST; Tam, CS; Prine, B; Agarwal, SK; Munasinghe, W; Zhu, M; Lash, LL; Desai, M; Cerri, E; Verdugo, M; Kim, SY; Humerickhouse, RA; Gordon, GB; Kipps, TJ; Roberts, AW
MLA Citation
Seymour, JF, Ma, S, Brander, DM, Choi, MY, Barrientos, J, Davids, MS, Anderson, MA, Beaven, AW, Rosen, ST, Tam, CS, Prine, B, Agarwal, SK, Munasinghe, W, Zhu, M, Lash, LL, Desai, M, Cerri, E, Verdugo, M, Kim, SY, Humerickhouse, RA, Gordon, GB, Kipps, TJ, and Roberts, AW. "Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study." The Lancet. Oncology (January 12, 2017).
PMID
28089635
Source
epmc
Published In
The Lancet Oncology
Publish Date
2017
DOI
10.1016/s1470-2045(17)30012-8

Quality of Life is Similar between Long-term Survivors of Indolent and Aggressive Non-Hodgkin Lymphoma.

Differences in quality of life (QOL) of long-term survivors of aggressive or indolent subtypes of non-Hodgkin lymphoma (NHL) have not been frequently evaluated. We assessed these differences by analyzing results of a large QOL survey of long-term NHL survivors. We hypothesized that the incurable nature of indolent NHL would relate to worse QOL in long-term survivors while the potentially cured long-term survivors of aggressive lymphoma would have better QOL. We found that QOL was similar between the two groups. Results suggest that patients with indolent NHL are coping well with their disease, yet experience some overall feelings of life threat.

Authors
Beaven, AW; Samsa, G; Zimmerman, S; Smith, SK
MLA Citation
Beaven, AW, Samsa, G, Zimmerman, S, and Smith, SK. "Quality of Life is Similar between Long-term Survivors of Indolent and Aggressive Non-Hodgkin Lymphoma." Cancer investigation 34.6 (July 5, 2016): 279-285.
PMID
27379565
Source
epmc
Published In
Cancer Investigation (Informa)
Volume
34
Issue
6
Publish Date
2016
Start Page
279
End Page
285
DOI
10.1080/07357907.2016.1194427

A phase II study of cyclophosphamide, etoposide, vincristine and prednisone (CEOP) Alternating with Pralatrexate (P) as front line therapy for patients with peripheral T-cell lymphoma (PTCL): final results from the T- cell consortium trial.

Peripheral T-cell lymphomas (PTCL) have suboptimal outcomes using conventional CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy. The anti-folate pralatrexate, the first drug approved for patients with relapsed/refractory PTCL, provided a rationale to incorporate it into the front-line setting. This phase 2 study evaluated a novel front-line combination whereby cyclophosphamide, etoposide, vincristine and prednisone (CEOP) alternated with pralatrexate (CEOP-P) in PTCL. Patients achieving a complete or partial remission (CR/PR) were eligible for consolidative stem cell transplantation (SCT) after 4 cycles. Thirty-three stage II-IV PTCL patients were treated: 21 PTCL-not otherwise specified (64%), 8 angioimmunoblastic T cell lymphoma (24%) and 4 anaplastic large cell lymphoma (12%). The majority (61%) had stage IV disease and 46% were International Prognostic Index high/intermediate or high risk. Grade 3-4 toxicities included anaemia (27%), thrombocytopenia (12%), febrile neutropenia (18%), mucositis (18%), sepsis (15%), increased creatinine (12%) and liver transaminases (12%). Seventeen patients (52%) achieved a CR. The 2-year progression-free survival and overall survival, were 39% (95% confidence interval 21-57) and 60% (95% confidence interval 39-76), respectively. Fifteen patients (45%) (12 CR) received SCT and all remained in CR at a median follow-up of 21·5 months. CEOP-P did not improve outcomes compared to historical data using CHOP. Defining optimal front line therapy in PTCL continues to be a challenge and an unmet need.

Authors
Advani, RH; Ansell, SM; Lechowicz, MJ; Beaven, AW; Loberiza, F; Carson, KR; Evens, AM; Foss, F; Horwitz, S; Pro, B; Pinter-Brown, LC; Smith, SM; Shustov, AR; Savage, KJ; Vose, JM
MLA Citation
Advani, RH, Ansell, SM, Lechowicz, MJ, Beaven, AW, Loberiza, F, Carson, KR, Evens, AM, Foss, F, Horwitz, S, Pro, B, Pinter-Brown, LC, Smith, SM, Shustov, AR, Savage, KJ, and Vose, JM. "A phase II study of cyclophosphamide, etoposide, vincristine and prednisone (CEOP) Alternating with Pralatrexate (P) as front line therapy for patients with peripheral T-cell lymphoma (PTCL): final results from the T- cell consortium trial." February 2016.
PMID
26627450
Source
epmc
Published In
British Journal of Haematology
Volume
172
Issue
4
Publish Date
2016
Start Page
535
End Page
544
DOI
10.1111/bjh.13855

A phase II study of cyclophosphamide, etoposide, vincristine and prednisone (CEOP) Alternating with Pralatrexate (P) as front line therapy for patients with peripheral T-cell lymphoma (PTCL): final results from the T- cell consortium trial

Authors
Advani, RH; Ansell, SM; Lechowicz, MJ; Beaven, AW; Loberiza, F; Carson, KR; Evens, AM; Foss, F; Horwitz, S; Pro, B; Pinter-Brown, LC; Smith, SM; Shustov, AR; Savage, KJ; Vose, JM
MLA Citation
Advani, RH, Ansell, SM, Lechowicz, MJ, Beaven, AW, Loberiza, F, Carson, KR, Evens, AM, Foss, F, Horwitz, S, Pro, B, Pinter-Brown, LC, Smith, SM, Shustov, AR, Savage, KJ, and Vose, JM. "A phase II study of cyclophosphamide, etoposide, vincristine and prednisone (CEOP) Alternating with Pralatrexate (P) as front line therapy for patients with peripheral T-cell lymphoma (PTCL): final results from the T- cell consortium trial." BRITISH JOURNAL OF HAEMATOLOGY 172.4 (February 2016): 535-544.
Source
wos-lite
Published In
British Journal of Haematology
Volume
172
Issue
4
Publish Date
2016
Start Page
535
End Page
544
DOI
10.1111/bjh.13855

Ascertainment, classification, and impact of neoplasm detection during prolonged treatment with dual antiplatelet therapy with prasugrel vs. clopidogrel following acute coronary syndrome.

Studies have suggested increased cancer incidence associated with long-term dual antiplatelet therapy (DAPT) for acute coronary syndrome (ACS). We evaluated cancer incidence and treatment-related differences in an analysis of DAPT for ACS.The Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes trial enrolled 9326 participants with ACS, who received aspirin plus clopidogrel or prasugrel. Median treatment exposure was 15 months. Cancer history and screening procedures were collected. Suspected non-benign neoplasm events were reported and adjudicated. The primary outcome was detection of new, non-benign neoplasm. Factors associated with neoplasm events, the relationship of these events to cardiovascular and bleeding endpoints, and treatment-related differences in neoplasm detection were studied. Among 9240 participants who received ≥1 dose of study drug, 1.8% had a confirmed neoplasm event. The efficacy composite of cardiovascular death, myocardial infarction, or stroke occurred more frequently among those with a neoplasm event vs. those without (18.2 vs. 13.5%) as did Global Use of Strategies to Open Occluded Coronary Arteries severe/moderate bleeding (11.2 vs. 1.5%). Screening rates were substantially higher in North America and Western Europe/Scandinavia vs. other regions. Factors most strongly associated with detection of neoplasm events were older age, region, male sex, and current/recent smoking. Among the pre-specified population without a history of neoplasm or previous curative treatment for neoplasm (n = 9105), the incidence of neoplasm events was similar with prasugrel vs. clopidogrel (1.8 vs. 1.7%; HR = 1.04; 95% CI 0.77-1.42; P = 0.79).Neoplasm events were infrequent during long-term DAPT after ACS, were associated with differential cancer-screening practices across regions, and the frequency of neoplasm detection was similar with prasugrel vs. clopidogrel.ClinicalTrials.gov identifier: NCT00699998.

Authors
Roe, MT; Cyr, DD; Eckart, D; Schulte, PJ; Morse, MA; Blackwell, KL; Ready, NE; Zafar, SY; Beaven, AW; Strickler, JH; Onken, JE; Winters, KJ; Houterloot, L; Zamoryakhin, D; Wiviott, SD; White, HD; Prabhakaran, D; Fox, KAA; Armstrong, PW; Ohman, EM
MLA Citation
Roe, MT, Cyr, DD, Eckart, D, Schulte, PJ, Morse, MA, Blackwell, KL, Ready, NE, Zafar, SY, Beaven, AW, Strickler, JH, Onken, JE, Winters, KJ, Houterloot, L, Zamoryakhin, D, Wiviott, SD, White, HD, Prabhakaran, D, Fox, KAA, Armstrong, PW, and Ohman, EM. "Ascertainment, classification, and impact of neoplasm detection during prolonged treatment with dual antiplatelet therapy with prasugrel vs. clopidogrel following acute coronary syndrome." European heart journal 37.4 (January 2016): 412-422.
PMID
26637834
Source
epmc
Published In
European Heart Journal (Elsevier)
Volume
37
Issue
4
Publish Date
2016
Start Page
412
End Page
422
DOI
10.1093/eurheartj/ehv611

Safe and Effective Treatment of Patients with Peripheral T-Cell Lymphoma (PTCL) with the Novel HDAC Inhibitor, Belinostat, in Combination with CHOP: Results of the Bel-CHOP Phase 1 Trial

Authors
Johnston, PB; Cashen, AF; Nikolinakos, PG; Beaven, AW; Barta, SK; Bhat, G; Song, T; Choi, MR; Allen, LF; de Vos, S; Oki, Y; Deng, C; Foss, FM
MLA Citation
Johnston, PB, Cashen, AF, Nikolinakos, PG, Beaven, AW, Barta, SK, Bhat, G, Song, T, Choi, MR, Allen, LF, de Vos, S, Oki, Y, Deng, C, and Foss, FM. "Safe and Effective Treatment of Patients with Peripheral T-Cell Lymphoma (PTCL) with the Novel HDAC Inhibitor, Belinostat, in Combination with CHOP: Results of the Bel-CHOP Phase 1 Trial." December 3, 2015.
Source
wos-lite
Published In
Blood
Volume
126
Issue
23
Publish Date
2015

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

Outcomes following splenectomy in patients with myeloid neoplasms.

BACKGROUND AND OBJECTIVES: Myeloid neoplasms are classified into five major categories. These patients may develop splenomegaly and require splenectomy to alleviate mechanical symptoms, to ameliorate transfusion-dependent cytopenias, or to enhance stem cell transplantation. The objective of this study was to determine which clinical variables significantly impacted morbidity, mortality, and survival in patients with myeloid neoplasms undergoing splenectomy, and to determine if operative outcomes have improved over time. METHODS: The records of all patients with myeloid neoplasms undergoing splenectomy from 1993 to 2010 were retrospectively reviewed. RESULTS: Eighty-nine patients (n = 89) underwent splenectomy for myeloid neoplasms. Over half of patients who had symptoms preoperatively had resolution of their symptoms post-splenectomy. The morbidity rate was 38%, with the most common complications being bleeding (14%) or infection (20%). Thirty-day mortality rate was 18% and median survival after splenectomy was 278 days. Decreased survival was associated with a diagnosis of myelodysplastic syndrome/myeloproliferative neoplasm, anemia, abnormal white blood cell count, and hypoalbuminemia. Patients who underwent stem cell transplantation did not show an increased risk for morbidity or mortality. CONCLUSIONS: Patients with myeloid neoplasms have a poor prognosis after splenectomy and the decision to operate is a difficult one, associated with high morbidity and mortality.

Authors
Rialon, KL; Speicher, PJ; Ceppa, EP; Rendell, VR; Vaslef, SN; Beaven, A; Tyler, DS; Blazer, DG
MLA Citation
Rialon, KL, Speicher, PJ, Ceppa, EP, Rendell, VR, Vaslef, SN, Beaven, A, Tyler, DS, and Blazer, DG. "Outcomes following splenectomy in patients with myeloid neoplasms." Journal of surgical oncology 111.4 (March 2015): 389-395.
PMID
25488568
Source
epmc
Published In
Journal of Surgical Oncology
Volume
111
Issue
4
Publish Date
2015
Start Page
389
End Page
395
DOI
10.1002/jso.23846

Outcomes following splenectomy in patients with myeloid neoplasms

© 2014 Wiley Periodicals, Inc.Background and Objectives: Myeloid neoplasms are classified into five major categories. These patients may develop splenomegaly and require splenectomy to alleviate mechanical symptoms, to ameliorate transfusion-dependent cytopenias, or to enhance stem cell transplantation. The objective of this study was to determine which clinical variables significantly impacted morbidity, mortality, and survival in patients with myeloid neoplasms undergoing splenectomy, and to determine if operative outcomes have improved over time. Methods: The records of all patients with myeloid neoplasms undergoing splenectomy from 1993 to 2010 were retrospectively reviewed. Results: Eighty-nine patients (n=89) underwent splenectomy for myeloid neoplasms. Over half of patients who had symptoms preoperatively had resolution of their symptoms post-splenectomy. The morbidity rate was 38%, with the most common complications being bleeding (14%) or infection (20%). Thirty-day mortality rate was 18% and median survival after splenectomy was 278 days. Decreased survival was associated with a diagnosis of myelodysplastic syndrome/myeloproliferative neoplasm, anemia, abnormal white blood cell count, and hypoalbuminemia. Patients who underwent stem cell transplantation did not show an increased risk for morbidity or mortality. Conclusions: Patients with myeloid neoplasms have a poor prognosis after splenectomy and the decision to operate is a difficult one, associated with high morbidity and mortality.

Authors
Rialon, KL; Speicher, PJ; Ceppa, EP; Rendell, VR; Vaslef, SN; Beaven, A; Tyler, DS; Blazer, DG
MLA Citation
Rialon, KL, Speicher, PJ, Ceppa, EP, Rendell, VR, Vaslef, SN, Beaven, A, Tyler, DS, and Blazer, DG. "Outcomes following splenectomy in patients with myeloid neoplasms." Journal of Surgical Oncology 111.4 (January 1, 2015): 389-395.
Source
scopus
Published In
Journal of Surgical Oncology
Volume
111
Issue
4
Publish Date
2015
Start Page
389
End Page
395
DOI
10.1002/jso.23846

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

Short Course of Bendamustine and Rituximab Followed By 90Y-Ibritumomab Tiuxetan in Patients with Chemotherapy-Naive Follicular Lymphoma: Results of Fol-Brite

Authors
Lansigan, F; Zaki, BI; Yen, SP; Winer, ES; Ryan, H; Findley, DL; Metzler, SR; Shaw, L; Tsui, A; MacKenzie, T; Beaven, AW
MLA Citation
Lansigan, F, Zaki, BI, Yen, SP, Winer, ES, Ryan, H, Findley, DL, Metzler, SR, Shaw, L, Tsui, A, MacKenzie, T, and Beaven, AW. "Short Course of Bendamustine and Rituximab Followed By 90Y-Ibritumomab Tiuxetan in Patients with Chemotherapy-Naive Follicular Lymphoma: Results of Fol-Brite." BLOOD 124.21 (December 6, 2014).
Source
wos-lite
Published In
Blood
Volume
124
Issue
21
Publish Date
2014

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

Addition of lenalidomide to rituximab, ifosfamide, carboplatin, etoposide (RICER) in first-relapse/primary refractory diffuse large B-cell lymphoma.

Relapsed/refractory diffuse large B-cell lymphoma (DLBCL) is associated with a poor prognosis. Outcomes are particularly poor following immunochemotherapy failure or relapse within 12 months of induction. We conducted a Phase I/II trial of lenalidomide plus RICE (rituximab, ifosfamide, carboplatin, and etoposide) (RICER) as a salvage regimen for first-relapse or primary refractory DLBCL. Dose-escalated lenalidomide was combined with RICE every 14 d. After three cycles of RICER, patients with chemosensitive disease underwent stem cell collection and consolidation with BEAM [BCNU (carmustine), etoposide, cytarabine, melphalan] followed by autologous stem cell transplantation (autoSCT). Patients who recovered from autoSCT toxicities within 90 d initiated maintenance treatment with lenalidomide 25 mg daily for 21 d every 28 d for 12 months. No dose-limiting or unexpected toxicities occurred with lenalidomide 25 mg plus RICE. Grade 3/4 haematological toxicities resolved appropriately, and planned dose density and dose intensity of RICER were preserved. No lenalidomide or RICE dose reductions were required in any of the three cycles. After two cycles of RICER, nine of 15 patients (60%) achieved a complete response, and two achieved a partial response (13%). Combining lenalidomide with RICE is feasible, and results in promising response rates (particularly complete response rates) in high-risk DLBCL patients.

Authors
Feldman, T; Mato, AR; Chow, KF; Protomastro, EA; Yannotti, KML; Bhattacharyya, P; Yang, X; Donato, ML; Rowley, SD; Carini, C; Valentinetti, M; Smith, J; Gadaleta, G; Bejot, C; Stives, S; Timberg, M; Kdiry, S; Pecora, AL; Beaven, AW; Goy, A
MLA Citation
Feldman, T, Mato, AR, Chow, KF, Protomastro, EA, Yannotti, KML, Bhattacharyya, P, Yang, X, Donato, ML, Rowley, SD, Carini, C, Valentinetti, M, Smith, J, Gadaleta, G, Bejot, C, Stives, S, Timberg, M, Kdiry, S, Pecora, AL, Beaven, AW, and Goy, A. "Addition of lenalidomide to rituximab, ifosfamide, carboplatin, etoposide (RICER) in first-relapse/primary refractory diffuse large B-cell lymphoma." British journal of haematology 166.1 (July 2014): 77-83.
PMID
24661044
Source
epmc
Published In
British Journal of Haematology
Volume
166
Issue
1
Publish Date
2014
Start Page
77
End Page
83
DOI
10.1111/bjh.12846

Ofatumumab-based chemoimmunotherapy is effective and well tolerated in patients with previously untreated chronic lymphocytic leukemia (CLL). Cancer. 2013;119:3788-96.

Authors
Shanafelt, T; Lanasa, MC; Call, TG; Beaven, AW; Leis, JF; LaPlant, B; Bowen, D; Conte, M; Jelinek, DF; Hanson, CA; Kay, NE; Zent, CS
MLA Citation
Shanafelt, T, Lanasa, MC, Call, TG, Beaven, AW, Leis, JF, LaPlant, B, Bowen, D, Conte, M, Jelinek, DF, Hanson, CA, Kay, NE, and Zent, CS. "Ofatumumab-based chemoimmunotherapy is effective and well tolerated in patients with previously untreated chronic lymphocytic leukemia (CLL). Cancer. 2013;119:3788-96." CANCER 120.6 (March 15, 2014): 926-926.
Source
wos-lite
Published In
Cancer
Volume
120
Issue
6
Publish Date
2014
Start Page
926
End Page
926
DOI
10.1002/cncr.28502

Addition of lenalidomide to rituximab, ifosfamide, carboplatin, etoposide (RICER) in first-relapse/primary refractory diffuse large B-cell lymphoma

Relapsed/refractory diffuse large B-cell lymphoma (DLBCL) is associated with a poor prognosis. Outcomes are particularly poor following immunochemotherapy failure or relapse within 12 months of induction. We conducted a Phase I/II trial of lenalidomide plus RICE (rituximab, ifosfamide, carboplatin, and etoposide) (RICER) as a salvage regimen for first-relapse or primary refractory DLBCL. Dose-escalated lenalidomide was combined with RICE every 14 d. After three cycles of RICER, patients with chemosensitive disease underwent stem cell collection and consolidation with BEAM [BCNU (carmustine), etoposide, cytarabine, melphalan] followed by autologous stem cell transplantation (autoSCT). Patients who recovered from autoSCT toxicities within 90 d initiated maintenance treatment with lenalidomide 25 mg daily for 21 d every 28 d for 12 months. No dose-limiting or unexpected toxicities occurred with lenalidomide 25 mg plus RICE. Grade 3/4 haematological toxicities resolved appropriately, and planned dose density and dose intensity of RICER were preserved. No lenalidomide or RICE dose reductions were required in any of the three cycles. After two cycles of RICER, nine of 15 patients (60%) achieved a complete response, and two achieved a partial response (13%). Combining lenalidomide with RICE is feasible, and results in promising response rates (particularly complete response rates) in high-risk DLBCL patients. © 2014 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Authors
Feldman, T; Mato, AR; Chow, KF; Protomastro, EA; Yannotti, KML; Bhattacharyya, P; Yang, X; Donato, ML; Rowley, SD; Carini, C; Valentinetti, M; Smith, J; Gadaleta, G; Bejot, C; Stives, S; Timberg, M; Kdiry, S; Pecora, AL; Beaven, AW; Goy, A
MLA Citation
Feldman, T, Mato, AR, Chow, KF, Protomastro, EA, Yannotti, KML, Bhattacharyya, P, Yang, X, Donato, ML, Rowley, SD, Carini, C, Valentinetti, M, Smith, J, Gadaleta, G, Bejot, C, Stives, S, Timberg, M, Kdiry, S, Pecora, AL, Beaven, AW, and Goy, A. "Addition of lenalidomide to rituximab, ifosfamide, carboplatin, etoposide (RICER) in first-relapse/primary refractory diffuse large B-cell lymphoma." British Journal of Haematology 166.1 (January 1, 2014): 77-83.
Source
scopus
Published In
British Journal of Haematology
Volume
166
Issue
1
Publish Date
2014
Start Page
77
End Page
83
DOI
10.1111/bjh.12846

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

Whole Genome and Exome Sequencing Defines The Genetic Landscape Of Hepatosplenic T-Cell Lymphoma

Authors
Scotland, P; Gaulard, P; Love, CL; Fataccioli, V; Travert, M; De Leval, L; Weisenburger, DD; Czader, M; Parihar, M; Nair, R; Sengar, M; Beaven, AW; Crow, JH; Miles, RR; Gordon, LI; Chadburn, A; Evens, AM; Gill, J; Fedoriw, YD; Richards, KL; Srivastava, G; Choi, WWL; Flowers, CR; Bernal-Mizrachi, L; Mann, KP; Naresh, K; Hsi, ED; Horna, P; Tao, J; Sun, Z; Long, K; Zhang, J; Dave, S
MLA Citation
Scotland, P, Gaulard, P, Love, CL, Fataccioli, V, Travert, M, De Leval, L, Weisenburger, DD, Czader, M, Parihar, M, Nair, R, Sengar, M, Beaven, AW, Crow, JH, Miles, RR, Gordon, LI, Chadburn, A, Evens, AM, Gill, J, Fedoriw, YD, Richards, KL, Srivastava, G, Choi, WWL, Flowers, CR, Bernal-Mizrachi, L, Mann, KP, Naresh, K, Hsi, ED, Horna, P, Tao, J, Sun, Z, Long, K, Zhang, J, and Dave, S. "Whole Genome and Exome Sequencing Defines The Genetic Landscape Of Hepatosplenic T-Cell Lymphoma." November 15, 2013.
Source
wos-lite
Published In
Blood
Volume
122
Issue
21
Publish Date
2013

Hepatosplenic T-Cell Lymphoma: Clinicopathological Features and Treatment Outcomes: Report From The North American Peripheral T-Cell Lymphoma Consortium

Authors
Shustov, AR; Wilson, WH; Beaven, AW; Savage, KJ; Carson, KR; Hernandez-Ilizaliturri, FJ; Cherian, S; Gooley, TA; Vose, JM
MLA Citation
Shustov, AR, Wilson, WH, Beaven, AW, Savage, KJ, Carson, KR, Hernandez-Ilizaliturri, FJ, Cherian, S, Gooley, TA, and Vose, JM. "Hepatosplenic T-Cell Lymphoma: Clinicopathological Features and Treatment Outcomes: Report From The North American Peripheral T-Cell Lymphoma Consortium." November 15, 2013.
Source
wos-lite
Published In
Blood
Volume
122
Issue
21
Publish Date
2013

Ofatumumab-based chemoimmunotherapy is effective and well tolerated in patients with previously untreated chronic lymphocytic leukemia (CLL).

BACKGROUND: Although rituximab-based chemoimmunotherapy (CIT) has substantially improved clinical outcomes in chronic lymphocytic leukemia (CLL), only 40% to 50% of patients achieve a complete remission (CR). There remains interest in identifying new approaches to improve the effectiveness of CIT. Ofatumumab is a fully human anti-CD20 monoclonal antibody with greater apparent single-agent activity than rituximab in CLL patients. METHODS: Previously untreated CLL patients in need of therapy received 6 cycles of CIT induction with pentostatin, cyclophosphamide, and ofatumumab (PCO) followed by response assessment. RESULTS: Of the 48 patients enrolled, 77% completed PCO induction. Adverse events during induction included grade 3+ hematologic toxicity (27%) and grade 3+ nonhematologic toxicity (23%). Median CD4 count after induction and 6 months later were 186 × 10(6)/L and 272 × 10(6) /L. The overall response rate was 96% (46 of 48 patients), and the CR rate was 46% (22 of 48 patients). Among the 38 patients who underwent minimal residual disease evaluation, 7 (18%) were negative for minimal residual disease. After median follow-up of 24 months, 10 (21%) patients have progressed and 8 (17%) have required retreatment. The efficacy and toxicity of ofatumumab-based CIT compare favorably to our historical trials of rituximab-based CIT using an identical chemotherapy backbone (n = 64). Time to retreatment also appeared longer for ofatumumab-based CIT (free of retreatment at 24 months: 86% [95% confidence interval = 75-99] versus 68% [95% confidence interval = 56-81] for rituximab-based CIT). CONCLUSIONS: Ofatumumab-based CIT is well tolerated in patients with previously untreated CLL. The efficacy of ofatumumab-based CIT compares favorably to historical trials of rituximab-based CIT, suggesting randomized trials comparing ofatumumab-based CIT and rituximab-based CIT should be considered.

Authors
Shanafelt, T; Lanasa, MC; Call, TG; Beaven, AW; Leis, JF; LaPlant, B; Bowen, D; Conte, M; Jelinek, DF; Hanson, CA; Kay, NE; Zent, CS
MLA Citation
Shanafelt, T, Lanasa, MC, Call, TG, Beaven, AW, Leis, JF, LaPlant, B, Bowen, D, Conte, M, Jelinek, DF, Hanson, CA, Kay, NE, and Zent, CS. "Ofatumumab-based chemoimmunotherapy is effective and well tolerated in patients with previously untreated chronic lymphocytic leukemia (CLL)." Cancer 119.21 (November 1, 2013): 3788-3796.
PMID
23922059
Source
pubmed
Published In
Cancer
Volume
119
Issue
21
Publish Date
2013
Start Page
3788
End Page
3796
DOI
10.1002/cncr.28292

PAK1 mediates resistance to PI3K inhibition in lymphomas.

PURPOSE: The phosphoinositide 3-kinase (PI3K) pathway is known to play an active role in many malignancies. The role of PI3K inhibition in the treatment of lymphomas has not been fully delineated. We sought to identify a role for therapeutic PI3K inhibition across a range of B-cell lymphomas. EXPERIMENTAL DESIGN: We selected three small molecule inhibitors to test in a panel of 60 cell lines that comprised diverse lymphoma types. We tested the selective PI3K inhibitor BKM120 and the dual PI3K/mTOR inhibitors BEZ235 and BGT226 in these cell lines. We applied gene expression profiling to better understand the molecular mechanisms associated with responsiveness to these drugs. RESULTS: We found that higher expression of the PAK1 gene was significantly associated with resistance to all three PI3K inhibitors. Through RNA-interference-mediated knockdown of the PAK1 gene, we showed a dramatic increase in the sensitivity to PI3K inhibition. We further tested a small-molecule inhibitor of PAK1 and found significant synergy between PI3K and PAK1 inhibition. CONCLUSION: Thus, we show that PI3K inhibition is broadly effective in lymphomas and PAK1 is a key modulator of resistance to PI3K inhibition.

Authors
Walsh, K; McKinney, MS; Love, C; Liu, Q; Fan, A; Patel, A; Smith, J; Beaven, A; Jima, DD; Dave, SS
MLA Citation
Walsh, K, McKinney, MS, Love, C, Liu, Q, Fan, A, Patel, A, Smith, J, Beaven, A, Jima, DD, and Dave, SS. "PAK1 mediates resistance to PI3K inhibition in lymphomas." Clin Cancer Res 19.5 (March 1, 2013): 1106-1115.
PMID
23300274
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
19
Issue
5
Publish Date
2013
Start Page
1106
End Page
1115
DOI
10.1158/1078-0432.CCR-12-1060

Ofatumumab-based chemoimmunotherapy is effective and well tolerated in patients with previously untreated chronic lymphocytic leukemia (CLL)

BACKGROUND Although rituximab-based chemoimmunotherapy (CIT) has substantially improved clinical outcomes in chronic lymphocytic leukemia (CLL), only 40% to 50% of patients achieve a complete remission (CR). There remains interest in identifying new approaches to improve the effectiveness of CIT. Ofatumumab is a fully human anti-CD20 monoclonal antibody with greater apparent single-agent activity than rituximab in CLL patients. METHODS Previously untreated CLL patients in need of therapy received 6 cycles of CIT induction with pentostatin, cyclophosphamide, and ofatumumab (PCO) followed by response assessment. RESULTS Of the 48 patients enrolled, 77% completed PCO induction. Adverse events during induction included grade 3+ hematologic toxicity (27%) and grade 3+ nonhematologic toxicity (23%). Median CD4 count after induction and 6 months later were 186 × 106/L and 272 × 106/L. The overall response rate was 96% (46 of 48 patients), and the CR rate was 46% (22 of 48 patients). Among the 38 patients who underwent minimal residual disease evaluation, 7 (18%) were negative for minimal residual disease. After median follow-up of 24 months, 10 (21%) patients have progressed and 8 (17%) have required retreatment. The efficacy and toxicity of ofatumumab-based CIT compare favorably to our historical trials of rituximab-based CIT using an identical chemotherapy backbone (n = 64). Time to retreatment also appeared longer for ofatumumab-based CIT (free of retreatment at 24 months: 86% [95% confidence interval = 75-99] versus 68% [95% confidence interval = 56-81] for rituximab-based CIT). CONCLUSIONS Ofatumumab-based CIT is well tolerated in patients with previously untreated CLL. The efficacy of ofatumumab-based CIT compares favorably to historical trials of rituximab-based CIT, suggesting randomized trials comparing ofatumumab-based CIT and rituximab-based CIT should be considered. Cancer 2013;119:3788-3796. © 2013 American Cancer Society.

Authors
Shanafelt, T; Lanasa, MC; Call, TG; Beaven, AW; Leis, JF; Laplant, B; Bowen, D; Conte, M; Jelinek, DF; Hanson, CA; al, E
MLA Citation
Shanafelt, T, Lanasa, MC, Call, TG, Beaven, AW, Leis, JF, Laplant, B, Bowen, D, Conte, M, Jelinek, DF, Hanson, CA, and al, E. "Ofatumumab-based chemoimmunotherapy is effective and well tolerated in patients with previously untreated chronic lymphocytic leukemia (CLL)." Cancer 119.21 (2013): 3788-3796.
Source
scival
Published In
Cancer
Volume
119
Issue
21
Publish Date
2013
Start Page
3788
End Page
3796
DOI
10.1002/cncr.28292

Pilot study of dacetuzumab in combination with rituximab and gemcitabine for relapsed or refractory diffuse large B-cell lymphoma

Dacetuzumab, a CD40-targeted, humanized antibody, mediates antitumor activity through effector cell functions and direct apoptotic signal transduction. Preclinical studies demonstrated synergistic activity between dacetuzumab, gemcitabine and rituximab against non-Hodgkin lymphoma in vivo. A phase 1b safety/efficacy study of dacetuzumab in combination with rituximab and gemcitabine was conducted in relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Patients received dacetuzumab at doses of 8 or 12 mg/kg IV weekly with rituximab (375 mg/m2 IV weekly in cycle 1, then every 28 days) and gemcitabine (1000 mg/m2 IV, days 1, 8 and 15, or days 1 and 15). Thirty-three patients with a median age of 67 years were enrolled. Common adverse events (≥15%) were grade 1/2 cytokine release syndrome, nausea, fatigue, thrombocytopenia, headache, decreased appetite, dyspnea, neutropenia, pyrexia, anemia, diarrhea, edema, constipation and cough. Dacetuzumab-related grade 3/4 adverse events occurred infrequently. Six of 30 evaluable patients achieved a complete response (CR) and eight a partial response (PR) per investigator assessment for an overall response rate (ORR) of 47%. © 2012 Informa UK, Ltd.

Authors
Forero-Torres, A; Bartlett, N; Beaven, A; Myint, H; Nasta, S; Northfelt, DW; Whiting, NC; Drachman, JG; Lobuglio, AF; Moskowitz, CH
MLA Citation
Forero-Torres, A, Bartlett, N, Beaven, A, Myint, H, Nasta, S, Northfelt, DW, Whiting, NC, Drachman, JG, Lobuglio, AF, and Moskowitz, CH. "Pilot study of dacetuzumab in combination with rituximab and gemcitabine for relapsed or refractory diffuse large B-cell lymphoma." Leukemia and Lymphoma 54.2 (2013): 277-283.
PMID
22775314
Source
scival
Published In
Leukemia & Lymphoma (Informa)
Volume
54
Issue
2
Publish Date
2013
Start Page
277
End Page
283
DOI
10.3109/10428194.2012.710328

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

Phase II Study of VEGF Inhibitor, PTK787/ZK222584, in Patients with Refractory or Relapsed Diffuse Large B-Cell Lymphoma

Authors
Brander, DM; Beaven, AW; Gockerman, JP; Diehl, LF; Gasparetto, C; Shea, TC; deCastro, C; Moore, JO; Rizzieri, DA
MLA Citation
Brander, DM, Beaven, AW, Gockerman, JP, Diehl, LF, Gasparetto, C, Shea, TC, deCastro, C, Moore, JO, and Rizzieri, DA. "Phase II Study of VEGF Inhibitor, PTK787/ZK222584, in Patients with Refractory or Relapsed Diffuse Large B-Cell Lymphoma." November 16, 2012.
Source
wos-lite
Published In
Blood
Volume
120
Issue
21
Publish Date
2012

Phase 1 Study of Lenalidomide and Decitabine for High and Intermediate 2 Risk MDS

Authors
Rao, A; Khan, G; Rizzieri, DA; Moore, JO; Gockerman, JP; Diehl, LF; Beaven, AW; Adams, D; Warzecho, J; Decastro, C
MLA Citation
Rao, A, Khan, G, Rizzieri, DA, Moore, JO, Gockerman, JP, Diehl, LF, Beaven, AW, Adams, D, Warzecho, J, and Decastro, C. "Phase 1 Study of Lenalidomide and Decitabine for High and Intermediate 2 Risk MDS." November 16, 2012.
Source
wos-lite
Published In
Blood
Volume
120
Issue
21
Publish Date
2012

Short Course of Bendamustine and Rituximab Followed by 90Y-Ibritumomab Tiuxetan in Patients with Chemotherapy-Naive Follicular Lymphoma: Early Results of "Fol-Brite"

Authors
Lansigan, F; Winer, E; Metzler, SR; Shaw, L; Alton, P; Foster, K; MacKenzie, T; Beaven, AW
MLA Citation
Lansigan, F, Winer, E, Metzler, SR, Shaw, L, Alton, P, Foster, K, MacKenzie, T, and Beaven, AW. "Short Course of Bendamustine and Rituximab Followed by 90Y-Ibritumomab Tiuxetan in Patients with Chemotherapy-Naive Follicular Lymphoma: Early Results of "Fol-Brite"." November 16, 2012.
Source
wos-lite
Published In
Blood
Volume
120
Issue
21
Publish Date
2012

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

Radiotherapy dose-response analysis for diffuse large B-cell lymphoma with a complete response to chemotherapy.

OBJECTIVE: To examine the efficacy of different radiation doses after achievement of a complete response to chemotherapy in diffuse large B-cell lymphoma (DLBCL). METHODS: Patients with stage I-IV DLBCL treated from 1995-2009 at Duke Cancer Institute who achieved a complete response to chemotherapy were reviewed. In-field control, event-free survival, and overall survival were calculated using the Kaplan-Meier method. Dose response was evaluated by grouping treated sites by delivered radiation dose. RESULTS: 105 patients were treated with RT to 214 disease sites. Chemotherapy (median 6 cycles) was R-CHOP (65%), CHOP (26%), R-CNOP (2%), or other (7%). Post-chemotherapy imaging was PET/CT (88%), gallium with CT (1%), or CT only (11%). The median RT dose was 30 Gy (range, 12-40 Gy). The median radiation dose was higher for patients with stage I-II disease compared with patients with stage III-IV disease (30 versus 24.5 Gy, p < 0.001). Five-year in-field control, event-free survival, and overall survival for all patients was 94% (95% CI: 89-99%), 84% (95% CI: 77-92%), and 91% (95% CI: 85-97%), respectively. Six patients developed an in-field recurrence at 10 sites, without a clear dose response. In-field failure was higher at sites ≥ 10 cm (14% versus 4%, p = 0.06). CONCLUSION: In-field control was excellent with a combined modality approach when a complete response was achieved after chemotherapy without a clear radiation dose response.

Authors
Dorth, JA; Prosnitz, LR; Broadwater, G; Beaven, AW; Kelsey, CR
MLA Citation
Dorth, JA, Prosnitz, LR, Broadwater, G, Beaven, AW, and Kelsey, CR. "Radiotherapy dose-response analysis for diffuse large B-cell lymphoma with a complete response to chemotherapy. (Published online)" Radiat Oncol 7 (June 21, 2012): 100-.
PMID
22720801
Source
pubmed
Published In
Radiation Oncology
Volume
7
Publish Date
2012
Start Page
100
DOI
10.1186/1748-717X-7-100

A phase I study evaluating ibritumomab tiuxetan (Zevalin®) in combination with bortezomib (Velcade®) in relapsed/refractory mantle cell and low grade B-cell non-Hodgkin lymphoma.

Proteasome inhibitors may inhibit DNA repair of radiation-induced strand breaks and adducts thereby making the combination of radioimmunotherapy and bortezomib a promising approach. Preclinical models demonstrate additive/synergistic effects from combining DNA damaging agents with proteasome inhibitors. This phase I trial combines ibritumomab tiuxetan with bortezomib. Twelve patients with relapsed/refractory mantle cell and low grade B-cell non-Hodgkin lymphoma were enrolled. Patients with prior radioimmunotherapy were prohibited. The maximum tolerated dose (MTD) was not reached. No dose limiting toxicities (DLTs) occurred in cohort 1 or 2. One of six patients on cohort 3 had DLTs of asthenia, dizziness and neuropathy. Grade 3/4 thrombocytopenia occurred in two patients (16%) and grade 3/4 neutropenia in three patients (25%). Five subjects (41.7%) had complete responses (CRs) and one patient had a partial response (8.3%) for an overall response rate (ORR) of 50%. The combination of standard dose ibritumomab tiuxetan and bortezomib at 1.5 mg/m(2) is well tolerated with a promising response rate.

Authors
Beaven, AW; Shea, TC; Moore, DT; Feldman, T; Ivanova, A; Ferraro, M; Ford, P; Smith, J; Goy, A
MLA Citation
Beaven, AW, Shea, TC, Moore, DT, Feldman, T, Ivanova, A, Ferraro, M, Ford, P, Smith, J, and Goy, A. "A phase I study evaluating ibritumomab tiuxetan (Zevalin®) in combination with bortezomib (Velcade®) in relapsed/refractory mantle cell and low grade B-cell non-Hodgkin lymphoma." Leuk Lymphoma 53.2 (February 2012): 254-258.
PMID
21812533
Source
pubmed
Published In
Leukemia & Lymphoma (Informa)
Volume
53
Issue
2
Publish Date
2012
Start Page
254
End Page
258
DOI
10.3109/10428194.2011.608445

Update on treatment of follicular non-Hodgkin's lymphoma: focus on potential of bortezomib.

Follicular lymphoma is predominantly managed as a chronic disease, with intermittent chemo/immunotherapy reserved for symptomatic progression. It is considered incurable with conventional treatments, and current therapeutic options are associated with significant toxicities that are especially limiting in older patients. Bortezomib (PS-341; Velcade(®)), a first-in-class drug targeting the proteolytic core subunit of the 26S proteasome, has emerged as a therapeutic alternative in follicular lymphoma, with promising preclinical data and efficacy in patients with other hematological malignancies. Several clinical trials were conducted with bortezomib for the treatment of non-Hodgkin's lymphoma. As a single agent, overall responses in follicular lymphoma varied greatly (16%-41%), with weekly bortezomib showing less neurotoxicity than twice-weekly regimens, but with concern about decreased responses. Combination with rituximab was projected to improve the efficacy of bortezomib, but this resulted in increased toxicities and questionable added benefit. Although the largest Phase III study in follicular lymphoma of bortezomib plus rituximab versus rituximab alone demonstrated a significant progression-free survival difference, the absolute difference was small (12.8 months versus 11 months). Combining bortezomib with established regimens, such as rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP), or rituximab-bendamustine also did not show definite benefit, and many of these studies did not meet their primary endpoint when bortezomib failed to improve responses or survival to the degree anticipated. In a disease where the goal of treatment is palliative and affected patients often have other medical and treatment-related comorbidities, decisions regarding therapies which carry risks of additional toxicities must be considered carefully. Conclusive evidence of the ability of bortezomib to improve patient outcomes meaningfully and to justify the added toxicity is lacking, but limitations in cross-trial comparisons are recognized. Large randomized trials and investigations of combinations with promising novel targeted agents will aid in determining the role of bortezomib, if any, in the future treatment of follicular lymphoma.

Authors
Brander, DM; Beaven, AW
MLA Citation
Brander, DM, and Beaven, AW. "Update on treatment of follicular non-Hodgkin's lymphoma: focus on potential of bortezomib." Patient preference and adherence 6 (January 2012): 239-251.
PMID
22536060
Source
epmc
Published In
Patient Preference and Adherence
Volume
6
Publish Date
2012
Start Page
239
End Page
251
DOI
10.2147/ppa.s23241

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

High Complete Response Rates with Dose Dense/Dose Intense Chemotherapy Plus Radioimmunotherapy in High Risk Diffuse Large B Cell and Mantle Cell Lymphoma

Authors
Beaven, AW; Rizzieri, DA; Powell, Z; Li, Z; Alton, P; Warzecho, J; Diehl, LF; Moore, JO; III, DCCM; Gockerman, JP
MLA Citation
Beaven, AW, Rizzieri, DA, Powell, Z, Li, Z, Alton, P, Warzecho, J, Diehl, LF, Moore, JO, III, DCCM, and Gockerman, JP. "High Complete Response Rates with Dose Dense/Dose Intense Chemotherapy Plus Radioimmunotherapy in High Risk Diffuse Large B Cell and Mantle Cell Lymphoma." November 18, 2011.
Source
wos-lite
Published In
Blood
Volume
118
Issue
21
Publish Date
2011
Start Page
1152
End Page
1152

Infusional mitoxantrone plus bolus melphalan as a stem cell transplant conditioning regimen for multiple myeloma.

This study combined infusional mitoxantrone with bolus melphalan as a transplant preparative regimen for multiple myeloma. Mitoxantrone was infused over 6 hr on days 6 and 5. Melphalan was given as a 15 min bolus on day 1 followed by autologous transplant on day 0. Thirty-five patients were enrolled; 57% of enrollees had received ≥ 2 prior treatments. The median overall survival was 5 years and 8 months, with 37% of the subjects alive >7 years posttransplantation. Myelosuppression and mucositis were the most frequent adverse events. This regimen is well tolerated and the survival compares well to other transplant trials.

Authors
Beaven, AW; Moore, DT; Sharf, A; Serody, JS; Shea, TC; Gabriel, DA
MLA Citation
Beaven, AW, Moore, DT, Sharf, A, Serody, JS, Shea, TC, and Gabriel, DA. "Infusional mitoxantrone plus bolus melphalan as a stem cell transplant conditioning regimen for multiple myeloma." Cancer Invest 29.3 (March 2011): 214-219.
PMID
21314330
Source
pubmed
Published In
Cancer Investigation (Informa)
Volume
29
Issue
3
Publish Date
2011
Start Page
214
End Page
219
DOI
10.3109/07357907.2010.550663

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

Feasibility of low-dose interleukin-2 therapy following T-cell-depleted nonmyeloablative allogeneic hematopoietic stem cell transplantation from HLA-matched or -mismatched family member donors.

INTRODUCTION: High relapse rates and infections remain primary causes of failure in nonmyeloablative transplantation. Interleukin-2 (IL-2) may stimulate the immune system and improve outcomes. The primary objective of this pilot study was to evaluate the feasibility of administering IL-2 following a T-cell-depleted nonmyeloablative hematopoietic stem cell transplant. METHODS: Patients received T-cell-depleted nonmyeloablative transplant from a matched or mismatched related donor. Those with allogeneic engraftment,

Authors
Rizzieri, DA; Crout, C; Storms, R; Golob, J; Long, GD; Gasparetto, C; Sullivan, KM; Horwitz, M; Chute, J; Lagoo, AS; Morris, A; Beaven, A; Yang, Y; Peterson, B; Li, Z; Chao, NJ
MLA Citation
Rizzieri, DA, Crout, C, Storms, R, Golob, J, Long, GD, Gasparetto, C, Sullivan, KM, Horwitz, M, Chute, J, Lagoo, AS, Morris, A, Beaven, A, Yang, Y, Peterson, B, Li, Z, and Chao, NJ. "Feasibility of low-dose interleukin-2 therapy following T-cell-depleted nonmyeloablative allogeneic hematopoietic stem cell transplantation from HLA-matched or -mismatched family member donors." Cancer Invest 29.1 (January 2011): 56-61.
PMID
21166499
Source
pubmed
Published In
Cancer Investigation (Informa)
Volume
29
Issue
1
Publish Date
2011
Start Page
56
End Page
61
DOI
10.3109/07357907.2010.535055

Early post transplant (F-18) 2-fluoro-2-deoxyglucose positron emission tomography does not predict outcome for patients undergoing auto-SCT in non-Hodgkin and Hodgkin lymphoma

Positron emission tomography (PET) in conjunction with computed tomography is a frequently used modality for staging patients with lymphoma. Utility of PET-computed tomography before or early following auto-SCT has not been as rigorously evaluated. We retrospectively analyzed patients who received auto-SCT for treatment of relapsed or refractory non-Hodgkins lymphoma or Hodgkins disease between the years of 1996 and 2007. Patients who had either a PET scan following salvage chemotherapy within 14 weeks of transplantation (pre-PET), and/or a PET scan 6-14 weeks following transplantation (post-PET) were included. A total of 90 patients were identified for analysis. The median follow-up time is 3.3 years, with a range of 0.13-12.0 years. The median PFS was 4.6 years, and median OS was 5.1 years. At the time of this analysis, 34 patients (37%) experienced disease relapse, and 25 (27%) of the patients died from disease progression. In multivariate Cox proportional hazards analysis, post-PET did not predict for outcome, pre-PET positivity predicted for decrease in PFS. In conclusion, post-PET scan did not predict for PFS or OS in multivariate analysis. Positive pre-PET scan did predict for PFS as seen in previous studies, and may help identify patients who would benefit from innovative post transplant therapies. © 2011 Macmillan Publishers Limited All rights reserved.

Authors
Palmer, J; Goggins, T; Broadwater, G; Chao, N; Horwitz, M; Beaven, A; Sullivan, K; Coleman, RE; Rizzieri, D
MLA Citation
Palmer, J, Goggins, T, Broadwater, G, Chao, N, Horwitz, M, Beaven, A, Sullivan, K, Coleman, RE, and Rizzieri, D. "Early post transplant (F-18) 2-fluoro-2-deoxyglucose positron emission tomography does not predict outcome for patients undergoing auto-SCT in non-Hodgkin and Hodgkin lymphoma." Bone Marrow Transplantation 46.6 (2011): 847-851.
PMID
20856212
Source
scival
Published In
Bone Marrow Transplantation
Volume
46
Issue
6
Publish Date
2011
Start Page
847
End Page
851
DOI
10.1038/bmt.2010.203

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

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

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

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

Sequential high-dose ifosfamide, carboplatin and etoposide with rituximab for relapsed Hodgkin and large B-cell non-Hodgkin lymphoma: increased toxicity without improvement in progression-free survival.

Non-cross resistant drugs given at high-dose intensity may maximise tumor cell kill leading to improved patient outcomes. We investigated the feasibility and efficacy of administering ifosfamide, carboplatin and etoposide +/- rituximab as sequential high-dose single agents. Twenty-two patients with relapsed/refractory Hodgkin lymphoma (n = 9) or non-Hodgkin (n = 13) lymphoma (NHL) were included. Therapy included: cycle 1 ifosfamide (15 g/m(2)), cycle 2 etoposide (900 mg/m(2)) and cycle 3 carboplatin (area under the curve 15). Patients with NHL received rituximab (375 mg/m(2)) with cycles 1 and 2. Blood stem cell collection was performed after etoposide. Primary endpoints were overall response (complete response (CR) + PR) and ability to mobilise stem cells after etoposide. Secondary endpoints were to assess the toxicity of the regimen and to evaluate the ability of patients to proceed to stem cell transplant (SCT). Overall response rate was 54% with CR in 4/22 (18%) subjects and PR in 8/22 (36%). Median progression-free survival was 15 months and overall survival has not been reached at 40 months. Thirteen participants proceeded to SCT. Grade 3/4 thrombocytopenia and neutropenia occurred in 58% of cycles and 91% of subjects respectively. Forty-five percent of patients required hospitalisation for toxicity and two patients died from complications of therapy. Sequential dose intense ifosfamide, etoposide, carboplatin +/- rituximab was more toxic and no more effective than the same drugs given in a conventional fashion.

Authors
Shea, TC; Beaven, AW; Moore, DT; Serody, JS; Gabriel, DA; Chao, N; Gockerman, JP; Garcia, RA; Rizzieri, DA
MLA Citation
Shea, TC, Beaven, AW, Moore, DT, Serody, JS, Gabriel, DA, Chao, N, Gockerman, JP, Garcia, RA, and Rizzieri, DA. "Sequential high-dose ifosfamide, carboplatin and etoposide with rituximab for relapsed Hodgkin and large B-cell non-Hodgkin lymphoma: increased toxicity without improvement in progression-free survival." Leuk Lymphoma 50.5 (May 2009): 741-748.
PMID
19358012
Source
pubmed
Published In
Leukemia & Lymphoma (Informa)
Volume
50
Issue
5
Publish Date
2009
Start Page
741
End Page
748
DOI
10.1080/10428190902853136

The effect of palifermin on chemotherapyand radiation therapy-induced mucositis: a review of the current literature.

Oral mucositis is a painful ulceration of the mucosal lining of the oropharynx. It occurs frequently in patients receiving radiation therapy and/or chemotherapy for solid tumors and has been reported in up to 98% of patients undergoing hematopoietic stem cell transplantation. The development of mucositis is associated with significant morbidity, including longer hospital stays, increased bacteremia, and pain that interferes with talking, eating, and sleeping. Palifermin, a recombinant humanized keratinocyte growth factor, is the first pharmacologic agent that has been Food and Drug Administration-approved to decrease the incidence and duration of mucositis in patients with hematologic malignancies receiving chemotherapy requiring hematopoietic stem cell transplantation support. Results from phase I/II trials suggest that it might also benefit patients receiving treatment for solid tumors; however, the results from ongoing phase III trials will need to be available and examined before it can be incorporated into general clinical practice for this patient population.

Authors
Beaven, AW; Shea, TC
MLA Citation
Beaven, AW, and Shea, TC. "The effect of palifermin on chemotherapyand radiation therapy-induced mucositis: a review of the current literature." Support Cancer Ther 4.4 (September 1, 2007): 188-197.
PMID
18632516
Source
pubmed
Published In
Supportive cancer therapy
Volume
4
Issue
4
Publish Date
2007
Start Page
188
End Page
197
DOI
10.3816/SCT.2007.n.014

Recombinant human keratinocyte growth factor palifermin reduces oral mucositis and improves patient outcomes after stem cell transplant.

Oral mucositis, the breakdown of the mucosal lining of the oropharynx, occurs as a result of a toxic insult to the normal epithelium of the oral mucosa. Typically this is seen after exposure to a toxic agent such as radiation or chemotherapy; therefore, it is a frequent problem for patients undergoing treatment for cancer. In clinical trials, mucositis has been reported in up to 98% of patients receiving high-dose chemotherapy followed by hematological stem cell transplant. When mucositis develops it causes severe patient symptoms such as pain, but it is also associated with inferior clinical outcomes including increased infection, narcotic use and even mortality. In clinical trials, palifermin, a recombinant humanized keratinocyte growth factor (rHuKGF), has demonstrated an ability to decrease the incidence and duration of mucositis. In the registrational phase III trial in patients undergoing stem cell transplant for hematological malignancies, only 63% of patients who received palifermin developed World Health Organization grade 3 or 4 mucositis compared to 98% of patients on the placebo arm (1). The patients on the palifermin arm also had a shorter duration of mucositis with significantly decreased pain, use of narcotics, need for total parenteral nutrition and febrile neutropenia. Based on these results, palifermin became the first drug that has been approved by the U.S. Food and Drug Administration (FDA) to decrease the incidence and duration of severe oral mucositis in patients with hematological malignancies receiving high-dose chemotherapy requiring hematopoietic stem cell support. The development of mucositis is also a problem for patients receiving treatment for nonhematological tumors. In clinical trials, mucositis has been reported in over 75% of patients receiving combined chemo-/radiotherapy for head and neck cancer or fluorouracil for metastatic colon cancer. Initial phase I and II clinical trials of palifermin have demonstrated a benefit in patients receiving chemotherapy with or without radiation therapy for solid tumors; however, large phase III trials need to be completed before palifermin can gain FDA approval for this indication.

Authors
Beaven, AW; Shea, TC
MLA Citation
Beaven, AW, and Shea, TC. "Recombinant human keratinocyte growth factor palifermin reduces oral mucositis and improves patient outcomes after stem cell transplant." Drugs Today (Barc) 43.7 (July 2007): 461-473. (Review)
PMID
17728847
Source
pubmed
Published In
Drugs of Today
Volume
43
Issue
7
Publish Date
2007
Start Page
461
End Page
473
DOI
10.1358/dot.2007.43.7.1119723

Adjuvant therapy for colorectal cancer: Yesterday, today, and tomorrow

Authors
Beaven, AW; Goldberg, RM
MLA Citation
Beaven, AW, and Goldberg, RM. "Adjuvant therapy for colorectal cancer: Yesterday, today, and tomorrow." ONCOLOGY-NEW YORK 20.14 (December 2006): 1844-1844.
Source
wos-lite
Published In
Oncology
Volume
20
Issue
14
Publish Date
2006
Start Page
1844
End Page
1844

Mitoxantrone and melphalan as conditioning regimen for autologous stem cell transplant for multiple myeloma.

Authors
Beaven, AW; Comeau, T; Sharf, A; Moore, DT; Serody, J; Shea, TC; Gabriel, DA
MLA Citation
Beaven, AW, Comeau, T, Sharf, A, Moore, DT, Serody, J, Shea, TC, and Gabriel, DA. "Mitoxantrone and melphalan as conditioning regimen for autologous stem cell transplant for multiple myeloma." BLOOD 108.11 (November 16, 2006): 834A-834A.
Source
wos-lite
Published In
Blood
Volume
108
Issue
11
Publish Date
2006
Start Page
834A
End Page
834A

Palifermin: a keratinocyte growth factor that reduces oral mucositis after stem cell transplant for haematological malignancies.

Mucositis occurs in < or = 98% of patients undergoing stem cell transplant for haematological malignancies and is associated with significant morbidity and mortality. Patients with severe mucositis have more pain, more difficulty with daily activities such as talking and eating, and are more likely to have bacteraemia. Palifermin is a keratinocyte growth factor that has been shown to decrease severity and duration of mucositis with a concurrent decrease in patient-reported symptoms and use of narcotics and total parenteral nutrition. Research is ongoing into palifermin's potential ability to decrease graft-versus-host disease and improve reconstitution of functional T lymphocytes after allogeneic stem cell transplant, to hasten wound healing and to reduce mucositis following external beam radiation therapy in solid tumour patients.

Authors
Beaven, AW; Shea, TC
MLA Citation
Beaven, AW, and Shea, TC. "Palifermin: a keratinocyte growth factor that reduces oral mucositis after stem cell transplant for haematological malignancies." Expert Opin Pharmacother 7.16 (November 2006): 2287-2299. (Review)
PMID
17059384
Source
pubmed
Published In
Expert Opinion on Pharmacotherapy
Volume
7
Issue
16
Publish Date
2006
Start Page
2287
End Page
2299
DOI
10.1517/14656566.7.16.2287

Adjuvant therapy for colorectal cancer: yesterday, today, and tomorrow.

During the 1980s, the only drug routinely used to treat colorectal carcinoma was single-agent fluorouracil (5-FU), a drug that had shown no proven benefit in the adjuvant setting. Since then, significant improvements in the overall management of colorectal cancer have been made. This review will compare today's standard of care for adjuvant colorectal carcinoma to that practiced 20 years ago. The authors examine key questions asked about adjuvant therapy and the answers that ultimately changed clinical practice standards and improved overall survival for patients diagnosed with this disease. In addition, this review explores whether 5-FU should be given as part of a multidrug regimen and which route of administration is best when this drug is given. Further, the authors delve into both the use of locally directed therapies to the liver or peritoneum to improve outcomes and the selection of patients to receive adjuvant chemotherapy. Finally, a look to the future shows monoclonal antibodies to be an avenue of great promise infighting colorectal cancer.

Authors
Beaven, AW; Goldberg, RM
MLA Citation
Beaven, AW, and Goldberg, RM. "Adjuvant therapy for colorectal cancer: yesterday, today, and tomorrow." Oncology (Williston Park) 20.5 (April 2006): 461-469. (Review)
PMID
16739745
Source
pubmed
Published In
Oncology
Volume
20
Issue
5
Publish Date
2006
Start Page
461
End Page
469

Long term effects on GVHD and survival following the use of G-CSF stimulated bone marrow versus G-CSF mobilized peripheral blood stem cells in HLA matched sibling transplant.

Authors
Beaven, AW; Shea, TC; Gabriel, DA; Comeau, T; Irons, R; Moore, DT; Lin, L; Sharf, A; Krasnov, C; Brecher, ME; Serody, J
MLA Citation
Beaven, AW, Shea, TC, Gabriel, DA, Comeau, T, Irons, R, Moore, DT, Lin, L, Sharf, A, Krasnov, C, Brecher, ME, and Serody, J. "Long term effects on GVHD and survival following the use of G-CSF stimulated bone marrow versus G-CSF mobilized peripheral blood stem cells in HLA matched sibling transplant." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
432B
End Page
432B
Show More