Biology and management of therapy-related acute promyelocytic leukemia

Abstract

Therapy-related acute promyelocytic leukemia (t-APL) has been increasingly reported after exposure to cytotoxic and/or immunosuppressive agents given for prior malignancies or autoimmune diseases. t-APL represents both a model for better understanding human leukemogenesis and an interesting therapeutic subset which requires specific adaptations for optimal management. We discuss here potential risk factors for t-APL development and the main biologic and clinical characteristics of t-APL as compared to de-novo APL.In addition, we review therapeutic results obtained in patients with t-APL receiving conventional retinoic acid and chemotherapy and discuss new treatment opportunities with minimal or no exposure to conventional cytotoxic agents. Genomic studies in patients at risk of t-APL are relevant to better adapt treatment for the primary disease and to implement monitoring during follow-up and early diagnosis of t-APL. Improved molecular characterization of t-APL may include next generation sequencing approaches to better identify distinguishing features as compared to de-novo APL. Early diagnosis of t-APL through careful monitoring of patients at higher risk, coupled to incorporation in the therapeutic armamentarium of novel effective agents such as arsenic trioxide could result in improved clinical outcome for these patients.