Ken Young

Overview:

I am a clinically-oriented diagnostic physician with clinical expertise in the pathologic diagnosis of hematologic cancers including tumors of the bone marrow, lymphoid tissue, spleen and pre-malignant hematologic conditions. Another area of interest is blood cancer classification with molecular and genetic profiling. In my research program, we focus on molecular mechanisms of tumor progression, cell-of-origin, biomarkers, and novel therapeutic strategies in lymphoma, myeloma and leukemia. In addition to patient care and translational research, medical education and scientific communication are also part of interest. Many residents, fellows, graduates and postdocs have worked and been trained in our program. We perform comprehensive clinical and research functions that include bone marrow, lymphoma pathology, clinical flow cytometry, cytogenetics, molecular diagnostics and outside services.

I am currently the director of hematopathology division that provides diagnostic consultation services and relevant specialized testing for patients with various types of acute and chronic leukemia, lymphoma and benign hematologic disorders. I am specialized in the diagnosis of hematological disorders, including acute and chronic leukemias, myelodysplastic syndromes, myeloproliferative neoplasms, B and T-cell lymphomas, Hodgkin lymphoma, cutaneous and orbital lymphomas and benign bone marrow and lymph node disorders. 

Positions:

Professor of Pathology

Pathology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1984

Zhejiang University (China)

Grants:

Publications:

Vulvar Primary Cutaneous CD8+ Aggressive Epidermotropic Cytotoxic T-Cell Lymphoma.

Cutaneous T-cell lymphomas may present with a clinical course that is incongruent with the associated histologic findings. Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma classically presents as an abrupt eruption of disseminated ulcerated annular plaques with aggressive behavior and a poor prognosis. Herein we describe a vulvar primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma with a locally aggressive clinical course that was strikingly responsive to radiation therapy. As aggressive therapy involving systemic chemotherapy is indicated for primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma, appropriate clinico-pathologic correlation is crucial for preventing potentially excessive or insufficient therapeutic intervention. Our case also highlights the pivotal role of both radiation therapy and infection control in the management of aggressive cutaneous vulvar lymphomas.
Authors
Morse, DC; Park, KE; Chitsazzadeh, V; Li, S; Young, K; Gunther, JR; Dabaja, BS; Duvic, M
MLA Citation
Morse, Daniel C., et al. “Vulvar Primary Cutaneous CD8+ Aggressive Epidermotropic Cytotoxic T-Cell Lymphoma.Int J Gynecol Pathol, vol. 40, no. 3, May 2021, pp. 229–33. Pubmed, doi:10.1097/PGP.0000000000000648.
URI
https://scholars.duke.edu/individual/pub1476576
PMID
33741766
Source
pubmed
Published In
Int J Gynecol Pathol
Volume
40
Published Date
Start Page
229
End Page
233
DOI
10.1097/PGP.0000000000000648

MYC protein expression does not correlate with MYC abnormalities detected by FISH but predicts an unfavorable prognosis in de novo acute myeloid leukemia.

While dysregulation of MYC has been implicated in acute myeloid leukemia (AML), the impact of MYC protein expression in AML is less well understood. We investigated the correlation of MYC protein expression by immunohistochemistry (MYC-IHC) with MYC abnormalities and prognosis in adult de novo AML. MYC-IHC in bone marrow of patients with untreated AML (n = 58) was assessed and scored as MYClow (0-40 % of blasts) or MYChigh (> 40 % of blasts). This was correlated with MYC abnormalities by fluorescence in situ hybridization (FISH) and prognosis in the context of cytogenetic risk stratification. Residual myeloid disease at the end of induction was assessed by flow cytometry. MYClow and MYChigh were detected in 24 (41 %) and 34 cases (59 %), respectively. Extra copies of MYC were present in 12 % of cases and were not correlated with level of MYC-IHC. No cases had MYC translocation or amplification. Compared to MYClow patients, MYChigh patients had a shorter overall survival in all cytogenetic risk groups (68 vs. 21 months, p = 0.006) and in the intermediate risk group (61 vs. 21 months, p = 0.046). MYChigh patients had a tendency towards detected residual disease at the end of induction in all cytogenetic risk and intermediate risk groups. Regardless of the underlying mechanisms of MYC dysregulation, high level of MYC protein is expressed in the majority of AML and correlated to worse prognosis. Further studies on MYC dysregulation in leukemogenesis and therapy targeting MYC aberration are warranted.
Authors
Chen, P; Redd, L; Schmidt, Y; Koduru, P; Fuda, F; Montgomery-Goecker, C; Kumar, K; Xu-Monette, Z; Young, K; Collins, R; Chen, W
MLA Citation
Chen, Pu, et al. “MYC protein expression does not correlate with MYC abnormalities detected by FISH but predicts an unfavorable prognosis in de novo acute myeloid leukemia.Leuk Res, vol. 106, July 2021, p. 106584. Pubmed, doi:10.1016/j.leukres.2021.106584.
URI
https://scholars.duke.edu/individual/pub1482372
PMID
33933715
Source
pubmed
Published In
Leuk Res
Volume
106
Published Date
Start Page
106584
DOI
10.1016/j.leukres.2021.106584

Molecular and genetic biomarkers implemented from next-generation sequencing provide treatment insights in clinical practice for Waldenström macroglobulinemia.

Waldenström macroglobulinemia (WM) is a distinct type of indolent lymphoplasmacytic lymphoma (LPL) with a high frequency of MYD88L265P mutation. Treatment for WM/LPL is highly variable in clinic and ibrutinib (a Bruton tyrosine kinase inhibitor, BTKi) has become a new treatment option for WM. To investigate the clinical impact of genetic alterations in WM, we assembled a large cohort of 219 WMs and 12 LPLs dividing into two subcohorts: a training cohort, patients sequenced by a same targeted 29-gene next-generation sequencing (NGS) panel, and a validation cohort, patients sequenced by allele specific-PCR or other targeted NGS panels. In both training and validation subcohorts, MYD88L265P and TP53 mutations showed favorable and adverse prognostic effects, respectively. CXCR4 nonsense/missense mutations (CXCR4NS/MS), cytogenetic complex karyotypes, and a family history of lymphoma/leukemia in first-degree relatives were associated with significantly worse clinical outcomes only or more in the validation subcohort. We further investigated the efficacy of various treatments and interaction with genetic factors in the entire cohort. Upfront dexamethasone usage was associated with poorer clinical outcomes in patients who received non-proteasome-containing chemotherapy as first-line treatment independent of genetic factors. Maintenance rituximab was associated with better survival. Ibrutinib/BTKi showed potential benefit in relapsed/refractory patients and patients without CXCR4NS/MS including those with TP53 mutations. In conclusion, genetic testing for MYD88L265P, TP53, and CXCR4 mutations and cytogenetic analysis provide important information for prognosis prediction and therapy selection. The findings in these study are valuable for improving treatment decisions on therapies available for WM/LPL patients with integration of NGS in clinic.
Authors
Wang, Y; Gali, VL; Xu-Monette, ZY; Sano, D; Thomas, SK; Weber, DM; Zhu, F; Fang, X; Deng, M; Zhang, M; Hagemeister, FB; Li, Y; Orlowski, RZ; Lee, HC; Young, KH
MLA Citation
Wang, Yingjun, et al. “Molecular and genetic biomarkers implemented from next-generation sequencing provide treatment insights in clinical practice for Waldenström macroglobulinemia.Neoplasia, vol. 23, no. 4, Apr. 2021, pp. 361–74. Pubmed, doi:10.1016/j.neo.2021.02.002.
URI
https://scholars.duke.edu/individual/pub1476516
PMID
33735664
Source
pubmed
Published In
Neoplasia
Volume
23
Published Date
Start Page
361
End Page
374
DOI
10.1016/j.neo.2021.02.002

A Novel Predictive Model for Idiopathic Multicentric Castleman Disease: The International Castleman Disease Consortium Study.

BACKGROUND: Patients with multicentric Castleman disease (MCD) who are negative for human immunodeficiency virus and human herpesvirus 8 are considered to have idiopathic MCD (iMCD). The clinical presentation of iMCD varies from mild constitutional symptoms to life-threatening symptoms or death. The treatment strategy varies from "watchful waiting" to high-dose chemotherapy. This diverse clinical presentation calls for a classification stratification system that takes into account the severity of the disease. SUBJECTS, MATERIALS, AND METHODS: We analyzed the clinical, laboratory, and pathologic abnormalities and treatment outcomes of 176 patients with iMCD (median follow-up duration 12 years) from the U.S. and China to better understand the characteristics and prognostic factors of this disease. This discovery set of iMCD results was confirmed from the validation set composed of additional 197 patients with iMCD organized from The International Castleman Disease Consortium. RESULTS: Using these data, we proposed and validated the iMCD international prognostic index (iMCD-IPI), which includes parameters related to patient characteristics (age > 40 years), histopathologic features (plasma cell variant), and inflammatory consequences of iMCD (hepatomegaly and/or splenomegaly, hemoglobin <80 g/L, and pleural effusion). These five factors stratified patients according to their performance status and extent of organ dysfunction into three broad categories: low risk, intermediate risk, and high risk. The iMCD-IPI score accurately predicted outcomes in the discovery study cohort, and the results were confirmed on the validation study cohort. CONCLUSION: This study represents the largest series of studies on patients with iMCD in the field and proposed a novel risk-stratification model for iMCD-IPI that could be used to guide risk-stratified treatment strategies in patients with iMCD. IMPLICATIONS FOR PRACTICE: Patients with idiopathic multicentric Castleman disease (iMCD) can benefit from care based on clinical symptoms and disease severity. This study in 176 patients with iMCD constructed an iMCD-IPI score based on five clinical factors, including age >40 years, plasmacytic variant subtype, hepatomegaly and/or splenomegaly, hemoglobin <80 g/L, and pleural effusion, and stratified patients into three risk categories: low risk, intermediate risk, and high risk. The predictive value was validated in an independent set of 197 patients with iMCD from The International Castleman Disease Consortium. The proposed novel model is valuable for predicting clinical outcome and selecting optimal therapies using clinical parameters.
Authors
Yu, L; Shi, M; Cai, Q; Strati, P; Hagemeister, F; Zhai, Q; Li, L; Fang, X; Li, J; Sun, R; Zhang, S; Yang, H; Wang, Z; Qian, W; Iwaki, N; Sato, Y; Zhang, L; Li, J; Oksenhendler, E; Xu-Monette, ZY; Young, KH
MLA Citation
Yu, Li, et al. “A Novel Predictive Model for Idiopathic Multicentric Castleman Disease: The International Castleman Disease Consortium Study.Oncologist, vol. 25, no. 11, Nov. 2020, pp. 963–73. Pubmed, doi:10.1634/theoncologist.2019-0986.
URI
https://scholars.duke.edu/individual/pub1457153
PMID
32852137
Source
pubmed
Published In
Oncologist
Volume
25
Published Date
Start Page
963
End Page
973
DOI
10.1634/theoncologist.2019-0986

Clinical Relevance of MYC/BCL2 and Cell of Origin in Patients with Relapsed Diffuse Large B-Cell Lymphoma Treated with Autologous Stem Cell Transplantation

<jats:p>Purpose: Dual expression of MYC and BCL2 proteins (Double Expressor Lymphoma-[DEL]) and MYC, BCL2 and /or BCL6 translocations (Double Hit Lymphoma-[DHL]) as well as the cell-of-origin (COO) are important prognostic factors in patients (pts) with diffuse large B-cell lymphoma (DLBCL) who are treated with standard chemo-immunotherapy. Data are limited regarding the prognostic impact and interdependence of these biomarkers on outcomes in pts with relapsed DLBCL treated with autologous stem cell transplantation (ASCT).</jats:p> <jats:p>Methods: Data from Pts with relapsed DLBCL who underwent ASCT at our center and in whom archived tumor material was available were analyzed. Cutoff values of 40% for MYC and 70% for BCL2 were established by immunohistochemistry (IHC). FISH cases for MYC and BCL2 were considered for evaluation if at least 200 tumor cell nuclei per core displayed reliable signals in the sections. COO classification was achieved by IHC methods according to both the Visco-Young and Choi algorithms. The majority of pts (81%) underwent chemo-mobilization of stem cells with rituximab for in-vivo purging; rituximab was also given on days+1 and +8 with BEAM conditioning (J Clin Oncol 2005; 23:2240-7; Clin Cancer Res 2018; 24:2304-11). The study was IRB-approved at our center.</jats:p> <jats:p>Results: 303 pts were evaluated; 169 (56%) met the criteria for DEL and 3 (1%) for DHL; 8 (3%) met criteria for both (DEL/DHL) and 97 (32%) for neither (non-DEL/non-DHL). Because of small size, the 3 pts with only DHL were excluded from this analysis. In addition, 8 pts (3%) had atypical DHL and their outcomes were analyzed separately. GCB classification was successful in 269 pts, and 119 pts (44%) were of the GCB subtype. Median age of the whole group was 60 years (range, 18-80); the male gender predominated (65%). The median number of prior lines of therapies was 2. At ASCT, 90% of pts had chemo-sensitive disease (64% CR, 26% PR), and 6% had small volume SD; IPI was ≥ 2 in 17% of pts and PET was positive in 26%. There were no statistically significant differences in pt characteristics between the subgroups of non-DEL/non-DHL, DEL, or DEL/DHL, with the exception of GCB distribution: 46% and 41% of non-DEL/non-DHL and DEL, respectively, were classified to be of the GCB subtype, whereas all 8 DEL/DHL were classified as non-GCB (P=0.002). With a median follow-up time among survivors of 50 months (range, 4-217 months), the 4-year overall survival (OS) rates of non-DEL/non-DHL, DEL and DEL/DHL subgroups were 65%, 59%, and 25%, respectively. There was no significant difference in OS between non-DEL/non-DHL and DEL subgroups (P=0.39), however a significant difference in OS was observed between the two subgroups compared to the DEL/DHL pts (P=0.034; Figure 1). Progression-free-survival (PFS) rates were higher for the non-DEL/non-DHL (4-year rate: 51%) and DEL (4-year rate: 49%) compared to DEL/DHL (4-year rate: 25%) subgroups, though not statistically different (P=0.22). A higher risk of non-relapse mortality was observed in the DEL/DHL group compared to the other 2 groups (hazard ratio [HR]=3.8, P=0.017). The 4-year OS and PFS rates for the atypical DHL were 67% and 33%, respectively. We also evaluated the interaction of COO with BCL-2 protein expression; we found that pts who had BCL2 (+) expression, had worse OS (HR=1.82; P=0.049) and a trend for worse PFS (HR=1.58; P=0.08) compared to BCL2 (-) pts. This interaction was more prominent however in GCB pts. The 4 year OS rates of GCB/BCL2(-) and GCB/BCL2(+) were 87% and 56%, respectively (P=0.030). The 4-year PFS rates were 88% and 47%, respectively (P=0.007) (Figure 2). The OS and PFS rates within non-GCB subgroups were similar regardless of BCL2 expression.</jats:p> <jats:p>Conclusions: Our study shows that pt subgroups who have both DEL/DHL DLBCL have inferior survival. Interestingly, we also found that pts who have DEL and non-DEL/non-DHL have similar outcomes after ASCT. BCL2 expression is an important prognostic factor in GCB lymphoma. Investigational studies combining targeted therapies in this setting are warranted.</jats:p> <jats:p /> <jats:sec> <jats:title>Disclosures</jats:title> <jats:p>Jabbour: Takeda: Consultancy, Research Funding; BMS: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Adaptive: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Cyclacel LTD: Research Funding. Molldrem:M. D. Anderson &amp; Astellas Pharma: Other: Royalties. Bashir:Imbrium: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; StemLine: Research Funding; Acrotech: Research Funding; Celgene: Research Funding. Kebriaei:Amgen: Research Funding; Pfizer: Honoraria; Jazz: Consultancy; Kite: Honoraria. Popat:Bayer: Research Funding; Incyte: Research Funding; Jazz: Consultancy. Westin:Novartis: Other: Advisory Board, Research Funding; Celgene: Other: Advisory Board, Research Funding; Janssen: Other: Advisory Board, Research Funding; MorphoSys: Other: Advisory Board; Curis: Other: Advisory Board, Research Funding; Genentech: Other: Advisory Board, Research Funding; Unum: Research Funding; Kite: Other: Advisory Board, Research Funding; Juno: Other: Advisory Board; 47 Inc: Research Funding. Qazilbash:Bioclinical: Consultancy; Amgen: Consultancy, Other: Advisory Board; Autolus: Consultancy; Genzyme: Other: Speaker. Champlin:Johnson and Johnson: Consultancy; Actinium: Consultancy; Sanofi-Genzyme: Research Funding.</jats:p> </jats:sec>
Authors
Wang, Y; Young, KH; Milton, DR; Ledesma, C; Jabbour, E; Xu-Monette, ZY; Molldrem, JJ; Anderlini, P; Alousi, AM; Bashir, Q; Daher, M; Fayad, LE; Iyer, SP; Kebriaei, P; Marin, D; Mehta, RS; Olson, AL; Popat, U; Samaniego, F; Westin, JR; Qazilbash, MH; Im, JS; Rondon, G; Gulbis, A; Champlin, RE; Khouri, IF
MLA Citation
Wang, Yingjun, et al. “Clinical Relevance of MYC/BCL2 and Cell of Origin in Patients with Relapsed Diffuse Large B-Cell Lymphoma Treated with Autologous Stem Cell Transplantation.” Blood, vol. 134, no. Supplement_1, American Society of Hematology, 2019, pp. 2021–2021. Crossref, doi:10.1182/blood-2019-126719.
URI
https://scholars.duke.edu/individual/pub1470246
Source
crossref
Published In
Blood
Volume
134
Published Date
Start Page
2021
End Page
2021
DOI
10.1182/blood-2019-126719

Research Areas:

Biomarkers, Pharmacological
Genetic Association Studies
Leukemia
Lymphoblastic leukemia
Lymphoma
Multiple Myeloma