An aggressive type of B-cell non-Hodgkin’s lymphoma characterized by rearrangements in 2 genes: usually MYC and BCL2 and or BCL6.
Occurs in a subset of patients who compromise less than 15% of patients with non-Hodgkin lymphoma and who have a chromosomal rearrangement involving CMYC in combination with a second rearrangement involving BCL2, or less frequently BCL6.
Most patients have a diagnosis of diffuse large B-cell lymphoma (DLBCL, B-cell lymhoma unclassifiable with features intermediate between DLBCL and Burkitt lymphoma, or more rarely follicular lymphoma.
One rearrangement involves the MYC gene, and the other involves the BCL2 gene or, less commonly, the BCL6 gene.
These lymphomas have a germinal center B-cell phenotype, express CD10 and are TDT negative with a high proliferative index.
Double-hit lymphoma (DHL) shares many features with two other types of B-cell lymphomas—diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma gene mutations.
Double hit lymphoma presents at a more advanced stage in middle age than older adults, resulting in a poor prognosis.
Most patients have aggressive, symptomatic disease with extranodal involvement, a high international prognostic index score, high levels of LDH.
Approximately five percent of DLBCLs and about 32 to 78 percent of Burkitt lymphomas have rearrangements of the MYC and BCL2/BCL6 genes and are thus called Double-hit lymphomas (DHL)
Patients with double-hit lymphoma often present with extranodoal involvement and have an abbreviated response to standard chemotherapy and frequent relapses and have CNS involvement at a higher rate than do patients who do not have CYMC rearrangements.
Most cases can be identified as being of the germinal center B-cell subtype and express MYC on immunohistochemistry.
Patients with MYC rearranged lymphoma have an risk of CNS involvement or relapse in the CNS compared to other patients with diffuse large B-cell lymphoma.
Most cases of double hit lymphoma fall into the general center B cell (GCB) subtype in the cell of origin classification.
Patients in whom MYCC is partnered with an immunoglobulin gene, most commonly the heavy chain have the most aggressive course and worst outcome compared with other gene partners.
Baseline CSF analysis suggested.
Associated with old age, making aggressive therapy difficult.
No standard treatment approach.
It is associated with a very short median survival of less than two years, but with intensified induction chemotherapy better outcomes occur than with standard RCHOP.
Median overall survival ranging from 4.5 months to 34 months in various series, compared with an historical median 2 year overall survival with R-CHOP.
In most cases R-CHOP is inadequate therapy, and a more intensive induction regimen is indicated.
R-CHOP treatment outcomes are much worse in patients with doublehit lymphoma versus non-doublehit DLBCL.
More aggressive chemotherapy regimens, such as those used in Burkett lymphoma with hyper-CVAF and other similar agents (R-EPOCH) improve progression free survival but not necessarily overall survival.
ASCT is considered for initial therapy.
Can occur in the setting of tranformation of underlying indolent lymphoma acquiring a MYC translocation.
Some patients with double hit lymphoma have extensive bone marrow disease and this is also associated with a high-risk of CNS involvement.
CAR-T therapy is promising.