The clinical characteristics and prognosis analysis of acute B-cell lymphoblastic leukemia with MEF2D fusions

To investigate the clinical characteristics and prognosis of acute B-cell lymphoblastic leukemia (B-ALL) patients with MEF2D fusions. We retrospectively analyzed 15 newly diagnosed MEF2D-positive B-ALL patients admitted to The First Affiliated Hospital of Soochow University between January 2021 and December 2024, confirmed via targeted RNA sequencing (RNA-seq) or reverse transcription multiplex PCR. Immunophenotypic, cytogenetic, and molecular mutation profiles were assessed, along with treatment responses. Among the 228 patients initially diagnosed with high-risk B-ALL, 15 patients (6.58%) were positive for the MEF2D fusions. Of these positive cases, extramedullary infiltration was observed in 5 cases, with co-occurring mutations including KRAS (n = 6) and NRAS (n = 4); 4 patients had complex karyotypes. The MEF2D-positive group exhibited significantly inferior overall survival (OS) (P < 0.001) and event-free survival (EFS) (P < 0.001) compared to the MEF2D-negative cohort. After induction therapy, 13 patients achieved complete remission (CR), while 2 with partial response (PR) attained CR following venetoclax (VEN)-combined reinduction. Thirteen patients received immunotherapy, with 9 bridging to allogeneic hematopoietic stem cell transplantation (allo-HSCT). Moreover, one patient proceeded directly to allo-HSCT post-chemotherapy CR. The OS was significantly higher in the transplantation group compared to the non-transplantation group (P < 0.001), but there was no statistical difference between the two groups according to allo-HSCT as a time-dependent variable (P = 0.36). Case 12 achieved negativity for MEF2D with Chidamide incorporated into the preconditioning regimen. Case 3 experienced early post-transplant relapse but achieved transient remission after Ven-combined treatment. At the last follow-up, 10 patients (66.7%) relapsed and 10 patients (66.7%) died each, with a median OS of 14 (5–34)months. B-ALL with MEF2D fusions frequently demonstrates multilineage involvement, poor response to conventional chemotherapy, and extramedullary infiltration. Incorporating venetoclax and the histone deacetylase inhibitor chidamide into induction, salvage, or preconditioning regimens may probably improve outcomes for MEF2D-positive patients, though certainly required further clinical validation.