Fitting double-hit lymphoma into the aggressive lymphoma spectrum: a square peg in a round hole?

Objective: When we look at diffuse large B-cell lymphomas, 5-7% are double hit lymphoma, 30-40% are double expressor lymphoma and 5-10% are triple hit lymphomas and they have an aggressive course. In our study, the efficacy of the dose-adjusted-R-EPOCH treatment regimen in the treatment of double hit lymphoma, double expressor lymphoma, triple hit lymphoma; triple expressor lymphoma and primary large B cell lymphomas of the mediastinum are presented. Materials and Methods: Thirty-six patients diagnosed with B-cell lymphoma who received dose-adjusted R-EPOCH treatment were included in the study. The patients were grouped cytogenetically according to the Bcl-2 and Bcl-6 rearrangement by MYC translocation. Response assessment with PET-CT was performed in patients whose planned therapy reached the number of cycles. Results: At the end of the treatment, 61% of the patients had a complete response, 3% had a partial response, and 8% had no response. During the follow-up, 9 of the patients died and while the treatment of 2 patients was still ongoing, the treatment regimen of 1 patient was changed. When the patients were evaluated, 2 had double hit lymphoma (complete response in 2 patients), 9 had double expressive lymphoma (5 patients had complete response, 2 patients had progressed disease, 1 patient died and 1 patient had a change in treatment), and 8 had triple expressor lymphoma (Complete response in 5 patients, death in 2 patients, and progressive disease in 1 patient). Conclusion: The dose-adjusted-R-EPOCH treatment regimen can also provide a high response rate in patients with lymphoma with a triple expressor cytogenetic subtype.

Download Full-text

How I treat double-hit lymphoma

Blood ◽

10.1182/blood-2017-04-737320 ◽

2017 ◽

Vol 130 (5) ◽

pp. 590-596 ◽

Cited By ~ 50

Author(s):

Jonathan W. Friedberg

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

Central Nervous System Involvement ◽

B Cell Lymphoma ◽

World Health ◽

Large B Cell Lymphoma ◽

Double Hit Lymphoma ◽

Increased Risk ◽

Double Hit ◽

Large B Cell

Abstract The 2016 revision of the World Health Organization (WHO) classification for lymphoma has included a new category of lymphoma, separate from diffuse large B-cell lymphoma, termed high-grade B-cell lymphoma with translocations involving myc and bcl-2 or bcl-6. These lymphomas, which occur in <10% of cases of diffuse large B-cell lymphoma, have been referred to as double-hit lymphomas (or triple-hit lymphomas if all 3 rearrangements are present). It is important to differentiate these lymphomas from the larger group of double-expressor lymphomas, which have increased expression of MYC and BCL-2 and/or BCL-6 by immunohistochemistry, by using variable cutoff percentages to define positivity. Patients with double-hit lymphomas have a poor prognosis when treated with standard chemoimmunotherapy and have increased risk of central nervous system involvement and progression. Double-hit lymphomas may arise as a consequence of the transformation of the underlying indolent lymphoma. There are no published prospective trials in double-hit lymphoma, however retrospective studies strongly suggest that aggressive induction regimens may confer a superior outcome. In this article, I review my approach to the evaluation and treatment of double-hit lymphoma, with an eye toward future clinical trials incorporating rational targeted agents into the therapeutic armamentarium.

Download Full-text

Double-Hit Lymphoma at Second Relapse of Burkitt-Like Lymphoma : A Case Report

Journal of Clinical and Experimental Hematopathology ◽

10.3960/jslrt.51.43 ◽

2011 ◽

Vol 51 (1) ◽

pp. 43-47 ◽

Cited By ~ 2

Author(s):

Hiroaki Tanaka ◽

Shinichiro Hashimoto ◽

Daijiro Abe ◽

Shio Sakai ◽

Toshiyuki Takagi

Keyword(s):

Case Report ◽

Double Hit Lymphoma ◽

Double Hit

Download Full-text

Double-Hit Lymphoma with t(8;14)(q24;q32) and t(12;14)(q24;q32) Chromosomal Translocations

Internal Medicine ◽

10.2169/internalmedicine.50.5815 ◽

2011 ◽

Vol 50 (21) ◽

pp. 2659-2662 ◽

Cited By ~ 7

Author(s):

Tomohiro Yamazaki ◽

Hitoshi Ohno

Keyword(s):

Chromosomal Translocations ◽

Double Hit Lymphoma ◽

Double Hit

Download Full-text

Synthesis Of Multiple Types Of Survival Data Within A Weibull Proportional Hazards Meta-Analysis: Treatment Outcomes In Patients With Double Hit Lymphoma (DHL)

Value in Health ◽

10.1016/j.jval.2015.03.034 ◽

2015 ◽

Vol 18 (3) ◽

pp. A6

Author(s):

S.J. Snedecor ◽

C. Howlett ◽

A. Mato

Keyword(s):

Treatment Outcomes ◽

Survival Data ◽

Proportional Hazards ◽

Meta Analysis ◽

Double Hit Lymphoma ◽

Double Hit

Download Full-text

Outcomes of Patients With Double-Hit Lymphoma Who Achieve First Complete Remission

Journal of Clinical Oncology ◽

10.1200/jco.2017.72.2157 ◽

2017 ◽

Vol 35 (20) ◽

pp. 2260-2267 ◽

Cited By ~ 57

Author(s):

Daniel J. Landsburg ◽

Marissa K. Falkiewicz ◽

Joseph Maly ◽

Kristie A. Blum ◽

Christina Howlett ◽

...

Keyword(s):

Complete Remission ◽

Intensive Therapy ◽

Front Line ◽

Term Survival ◽

Disease Response ◽

Line Therapy ◽

Double Hit Lymphoma ◽

Double Hit ◽

First Complete Remission

Purpose Patients with double-hit lymphoma (DHL) rarely achieve long-term survival following disease relapse. Some patients with DHL undergo consolidative autologous stem-cell transplantation (autoSCT) to reduce the risk of relapse, although the benefit of this treatment strategy is unclear. Methods Patients with DHL who achieved first complete remission following completion of front-line therapy with either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or intensive front-line therapy, and deemed fit for autoSCT, were included. A landmark analysis was performed, with time zero defined as 3 months after completion of front-line therapy. Patients who experienced relapse before or who were not followed until that time were excluded. Results Relapse-free survival (RFS) and overall survival (OS) rates at 3 years were 80% and 87%, respectively, for all patients (n = 159). Three-year RFS and OS rates did not differ significantly for autoSCT (n = 62) versus non-autoSCT patients (n = 97), but 3-year RFS was inferior in patients who received R-CHOP compared with intensive therapy (56% v 88%; P = .002). Three-year RFS and OS did not differ significantly for patients in the R-CHOP or intensive therapy cohorts when analyzed by receipt of autoSCT. The median OS following relapse was 8.6 months. Conclusion In the largest reported series, to our knowledge, of patients with DHL to achieve first complete remission, consolidative autoSCT was not associated with improved 3-year RFS or OS. In addition, patients treated with R-CHOP experienced inferior 3-year RFS compared with those who received intensive front-line therapy. When considered in conjunction with reports of patients with newly diagnosed DHL, which demonstrate lower rates of disease response to R-CHOP compared with intensive front-line therapy, our findings further support the use of intensive front-line therapy for this patient population.

Download Full-text