Leukemic phase of MYC/BCL2 double-hit high-grade B-cell lymphoma: A report of 35 cases

We report 35 patients who had a leukemic phase of diffuse large B-cell lymphoma/high-grade B-cell lymphoma with MYC and BCL2 rearrangements, also known as double-hit lymphoma (DHL). There were 23 men and 12 women with a median age of 57 years (range, 29-82). Eight patients had an established DHL diagnosis and subsequently developed a leukemic phase of disease and 27 presented with DHL and a leukemic phase of disease at initial diagnosis. Thirty patients had not received any therapy specific for DHL at time of diagnosis. For these 30 patients, the median leukocyte count was 16.6 × 10⁹/L (range, 1.6-191.3) and the median percentage of lymphoma cells in the blood was 39 % (range, 10-97). Many patients presented with a clinical picture mimicking acute leukemia. Laboratory studies revealed elevated serum lactate dehydrogenase levels in all patients assessed, with a median level of 7507 U/L (range, 377-39,022). All patients had bone marrow involvement, with a median of 82% lymphoma cells in aspirate smears and approximately 80% replacement in biopsy specimens. Twenty-nine of 31 (94%) patients with complete information had extramedullary disease, most commonly lymph nodes. Immunophenotypic analysis showed a CD10-positive, germinal center B-cell immunophenotype in 34 cases. Conventional cytogenetic analysis was successful in 27 cases, all showing a complex karyotype. MYC partners were known in 22 cases, with immunoglobulin (IG) gene partners in 19 and non-IG partners in 3 cases. Despite treatment with chemotherapy regimens, overall survival was poor with a median of 7 months from onset of leukemic phase of disease. In summary, a small subset of patients with DHL can present with or develop a leukemic phase of disease which is a harbinger of very poor prognosis.