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Challenges and Opportunities for High-grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangement (Double-hit Lymphoma)

Zeng, Dongfeng, MD*,†; Desai, Aakash, MD*; Yan, Fangfang, MS*; Gong, Tiejun, MD*,‡; Ye, Haige, MD*,§; Ahmed, Makhdum, MD*; Nomie, Krystle, PhD*; Romaguera, Jorge, MD*; Champlin, Richard, MD; Li, Shaoying, MD; Wang, Michael, MD*

American Journal of Clinical Oncology: March 2019 - Volume 42 - Issue 3 - p 304–316
doi: 10.1097/COC.0000000000000427
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The most common subtype of non-Hodgkin lymphoma, diffuse large B-cell lymphoma, is cured in approximately two thirds of patients after initial therapy. The remaining one-third of patients who suffer relapse or become refractory have very poor survival outcomes despite salvage chemotherapy with or without stem cell transplantation. A considerable proportion of relapsed or refractory large B cells belong to the WHO subtype known as high-grade B-cell lymphoma with rearrangement of MYC and BCL2 and/or BCL6, also known as double-hit lymphoma (DHL). Most DHL patients present with Ann Arbor’s stage III/IV, a comparatively higher rate of extranodal involvement including bone marrow and central nervous system infiltration, high levels of lactate dehydrogenase, and an elevated Ki67 expression in the tumor cells. Newer therapeutic approaches, including targeted therapy against BCL2, MYC, or other associated pathways, are needed. In addition, recent therapies that harness the immune system, such as checkpoint inhibitors and chimeric antigen receptor T-cell therapy, are changing the paradigm of treatment for non-Hodgkin lymphoma and could impact the outcome of DHL.

Departments of *Lymphoma and Myeloma

Stem Cell Transplantation and Cellular Therapy, Division of Cancer Medicine

Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX

Department of Hematology, Xinqiao Hospital, the Third Military Medical University, Chongqing

Institute of Hematology and Oncology, Harbin First Hospital, Harbin

§Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

The authors declare no conflicts of interest.

Reprints: Michael Wang, MD, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. E-mail: miwang@mdanderson.org.

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