Therapy-Related Tp53-Mutated Precursor B-Cell Acute Lymphoblastic Leukemia Arising During Lenalidomide Maintenance Following Autologous Stem Cell Transplantation for Multiple Myeloma

Abstract

Therapy-related acute lymphoblastic leukemia (t-ALL) is a rare but increasingly recognized complication of cytotoxic therapy. We report a case of TP53-mutated precursor B-cell acute lymphoblastic leukemia arising in a patient with multiple myeloma treated with CyBorD induction, autologous stem cell transplantation, and prolonged lenalidomide maintenance.The patient presented with persistent cytopenias approximately six years after transplantation. Bone marrow evaluation demonstrated Philadelphia chromosome–negative B-ALL with a TP53 mutation at high variant allele frequency. The clinical course was complicated by infectious and treatment-related toxicities, necessitating de-escalation to maintenance therapy.This case highlights the emerging recognition of therapy-related B-ALL in multiple myeloma, the role of lenalidomide exposure, and the challenges in management due to adverse disease biology and patient-related factors.