Double-hit and double-protein-expression lymphomas: aggressive and refractory lymphomas.

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Double-hit lymphoma (DHL) is an aggressive lymphoma subtype defined by MYC and BCL2 gene rearrangements.
• DHL is associated with a poor prognosis, rapid progression, and resistance to standard treatments.
• The definition has evolved to include diffuse large B-cell lymphoma (DLBCL) with MYC translocations and BCL2 or BCL6 involvement.

Purpose of the Study:

• To review the evolving definitions and clinical characteristics of double-hit lymphomas.
• To discuss the clinical course and treatment challenges associated with DHL and double-protein-expression lymphomas (DPLs).
• To highlight the need for novel therapeutic approaches in managing these aggressive lymphomas.

Main Methods:

• Literature review of studies defining and characterizing double-hit lymphomas.
• Analysis of clinical data comparing DHL, DPLs, and standard DLBCL.
• Review of current treatment strategies and emerging therapies.

Main Results:

• DHL is characterized by MYC and BCL2 gene rearrangements, leading to aggressive disease.
• Immunohistochemical double-protein-expression lymphomas (DPLs) show similar but potentially slightly better outcomes than DHL.
• Both DHL and DPLs exhibit worse outcomes than standard DLBCL, with significant overlap.
• Current treatments are insufficient for long-term survival in DHL and DPLs.

Conclusions:

• Double-hit lymphomas, both genetic (DHL) and protein-expression (DPL) types, represent a challenging clinical entity.
• Despite aggressive treatments, cure and long-term survival remain elusive for patients with these lymphomas.
• The development of novel therapeutic agents is crucial for improving outcomes in patients with double-hit lymphomas.