Efficacy and safety of mini-CVD combined with venetoclax and azacitidine in acute leukemia of ambiguous lineage: A single-center retrospective study

Abstract Background:Acute leukemias of ambiguous lineage (ALAL) is a rare type of hematologic malignancies with poor outcomes. Currently, the treatment approaches for this type of leukemia globally lack standardized protocols and exhibit significant heterogeneity, necessitating the exploration of novel, targeted approaches. Methods: We retrospectively analyzed the clinical characteristics, efficacy, and safety of 13 newly diagnosed ALAL patients who received induction therapy with the mini-CVD regimen (cyclophosphamide, vincristine, dexamethasone) combined with venetoclax and azacitidine . Results: The cohort comprised 8 males and 5 females, with a median age of 53 years (range, 28–73 years). Recurrent genetic abnormalities were observed in 4 patients (30.8%), including KMT2A rearrangement (2 cases), EVI1 rearrangement (1 case), and CALM-AF10 fusion (1 case). Analysis of next-generation sequencing gene mutation results showed a mutational spectrum dominated by mutations associated with myeloid neoplasms, with RUNX1 (30.8%) and IKZF1 (23.1%) mutations being most frequent. Among this cohort, 92.3% of patients (12/13) achieved complete remission (CR), and 84.6% (11/13) remained alive in CR as of the last follow-up. One patient died due to primary resistance with sustained disease progression, while another succumbed to post-transplantation complications. Of the 12 patients who achieved CR, 2 (15.4%) experienced relapse, 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. Conclusion: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.