Efficacy and safety of mini-cvd combined with venetoclax and azacitidine in philadelphia chromosome-negative acute leukemia of ambiguous lineage: a single-center retrospective study

Acute leukemias of ambiguous lineage (ALAL) is a rare type of hematologic malignancies with poor outcomes. Currently, the treatment for this type of leukemia lack standardized protocols and exhibit significant heterogeneity, necessitating the exploration of novel, targeted approaches. We retrospectively analyzed the clinical characteristics, efficacy, and safety of 13 newly diagnosed Philadelphia chromosome (Ph)-negative ALAL patients between May 2022 and March 2025, who received induction therapy with the mini-CVD regimen (cyclophosphamide, vincristine, dexamethasone) combined with venetoclax and azacitidine. The cohort comprised 8 males and 5 females, with a median age of 53 years (range, 28-73 years). Among this cohort, 92.3% of patients (12/13) achieved complete remission (CR). Three patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) during CR1, and one patient received salvage allo-HSCT following relapse. With a median follow-up of 9.0 months (range 1.2-35.4 months), the overall survival rate was 84.6% (11/13). One patient died due to primary resistance with sustained disease progression, and another succumbed to post-transplantation complications. Of the 12 patients who achieved CR, 2 (15.4%) experienced relapsed, but both attained a second CR after salvage therapy. During induction therapy, the overall incidence of infection was 76.9% (10/13), with the majority being pulmonary infections (5/10). Notably, there was no death during induction therapy. Our data demonstrated that this regimen showed a high CR rate, with manageable toxicity, offering a promising therapeutic approach for this rare and challenging leukemia subtype.