Allogeneic hematopoietic cell transplantation for therapy-related hematological malignancies in patients with multiple myeloma.

Improved survival in multiple myeloma (MM) patients after high-dose chemotherapy, autologous hematopoietic cell transplantation (auto-HCT), and novel agents has led to an increasing incidence of therapy-related hematological malignancies (t-HM), although optimal management remains unclear, particularly the role of allogeneic HCT (allo-HCT). We conducted a retrospective single-center study of adult MM patients who underwent first auto-HCT between 2010 and 2025 and subsequently developed t-HM, analyzing clinical, molecular, cytogenetic features, treatment strategies, and outcomes, with a focus on allo-HCT. Among 519 patients, 23 (4.4%) developed t-HM, including therapy-related acute myeloid leukemia (43%), myelodysplastic syndrome (35%), and B-cell acute lymphoblastic leukemia (17%), with a median latency of 58.7 months after auto-HCT. High-risk genetics were common, including TP53 mutations in 52% and complex cytogenetics in 35%. Fourteen patients (61%) underwent allo-HCT, mainly with reduced-intensity conditioning. Median overall survival (OS) for the cohort was 31.5 months, while patients receiving allo-HCT had significantly superior OS compared with non-transplanted patients (median not reached vs. 2.5 months; P = 0.046). Therapy-related hematologic malignancies after MM treatment are uncommon but aggressive and genetically high-risk. In this cohort, allo-HCT was associated with improved survival and may represent a potentially curative approach in selected patients despite substantial toxicity.