Chapter 101: Burkitt Lymphoma

SUMMARY

Burkitt lymphoma is one of the highly aggressive B-cell lymphomas. It was the first tumor to be etiologically associated with (a) a virus, specifically Epstein-Barr virus, (b) a specific translocation involving the MYC oncogene, and (c) one of the first cancers shown to be curable by chemotherapy alone. It presents in three clinically distinct forms: endemic, sporadic, and immunodeficiency associated. BL is an uncommon form of lymphoma in adults, with an incidence of approximately 1200 patients per year in the United States. Over the past decade, the definition of BL has been refined, largely as a consequence of improvements in immunohistochemical, cytogenetic, and molecular diagnostic techniques. Transcriptional profiling has more clearly defined BL at the molecular level, and whole-genome sequencing has expanded our understanding of the mutational landscape that underlies this disease. Despite these refinements in diagnostic criteria, the differential diagnosis includes several aggressive lymphomas, including a group of patients with a diagnosis defined by the World Health Organization (WHO) as high-grade B-cell lymphoma with MYC and BCL2 or BCL6 rearrangements and a new WHO provisional entity called Burkitt-like lymphoma with chromosome 11q aberration. BL is a highly curable malignancy in the modern therapeutic era. The majority of younger patients are cured with intensive chemotherapeutic regimens, and increasing efficacy has been demonstrated with reduced-intensity treatments in older patients. Remaining challenges include the optimal management of older patients, the development of therapy for patients with relapsed or refractory disease, and the translation of gains made in treatment to the management of endemic disease.

Acronyms and Abbreviations

AID, activation-induced cytidine deaminase; ALL, acute lymphoblastic leukaemia; ASCT, autologous stem cell transplantation; B-ALL, acute B-cell lymphoblastic leukemia; BET, bromodomain and extraterminal; BL, Burkitt lymphoma; B-LBL, B-cell lymphoblastic lymphoma; CODOX-M/IVAC, cyclophosphamide, doxorubicin, vincristine, methotrexate, ifosfamide, etoposide, and high-dose cytarabine, with intrathecal cytarabine and methotrexate; DHL, double-hit lymphoma; DLBCL, diffuse large B-cell lymphoma; EBER, Epstein-Barr-virus–encoded RNA; eBL, endemic Burkitt lymphoma; EBNA, Epstein-Barr nuclear antigen; EBV, Epstein-Barr virus; FAB, French, American, British; FISH, fluorescence in situ hybridization; GEP, gene-expression profiling; HAART, highly active antiretroviral therapy; HIV, human immunodeficiency virus; hyper-CVAD, fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone; ID, inhibitor of DNA binding protein; Ig, immunoglobulin; LBL, lymphoblastic lymphoma; LDH, lactate dehydrogenase; mBL, molecular Burkitt lymphoma; LMP1, latent membrane protein 1; NCI, National Cancer Institute; NHL, non-Hodgkin lymphoma; PTLD, posttransplantation lymphoproliferative disease; R-EPOCH, etoposide, vincristine, and doxorubicin, with bolus rituximab, cyclophosphamide, and steroids; SEER, Surveillance, Epidemiology, and End Results Program; Tdt, terminal deoxynucleotidyl transferase; Bim, bcl2 interacting mediator of cell death or Bcl2-like 11; WHO, World Health Organization.