Double hit lymphoma: How do we define it and how do we treat it?

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Double/triple hit lymphoma (DHL/THL) is a distinct subtype of high-grade B-cell lymphoma, comprising 5-10% of diffuse large B-cell lymphoma cases.
• Also known as high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements under WHO 2016 classification.
• This lymphoma subtype exhibits a poor response to standard chemotherapy, highlighting the need for novel therapeutic approaches.

Purpose of the Study:

• To review current diagnostic strategies for identifying double/triple hit lymphoma, focusing on immunohistochemical profiling for case stratification.
• To provide a comprehensive overview of frontline and relapsed treatment options based on existing literature.
• To discuss the management of central nervous system (CNS) involvement and future research directions.

Main Methods:

• Literature review of diagnostic criteria and treatment outcomes for high-grade B-cell lymphomas with MYC and BCL2/BCL6 rearrangements.
• Analysis of immunohistochemical techniques for screening and diagnosing double/triple hit lymphoma.
• Evaluation of current clinical trial data and published studies on therapeutic interventions.

Main Results:

• Diagnosis requires identification of MYC and BCL2/BCL6 translocations, with immunohistochemistry serving as a viable initial screening tool.
• Standard chemotherapy yields poor outcomes, necessitating exploration of alternative treatment strategies.
• Central nervous system (CNS) involvement is a significant risk factor requiring specific management protocols.

Conclusions:

• Stratification using immunohistochemical profiling can aid in diagnosing double/triple hit lymphoma.
• Effective management strategies for both frontline and relapsed disease are crucial.
• Addressing CNS involvement and advancing research are key to improving patient outcomes.