تسجيل الدخول

تسجيل

Hematopoietic Stem Cell Transplantation for Therapy-Related and Secondary Acute Myeloid Leukemia

المؤلف:  Hoffman, R., Benz, E. J., Silberstein, L. E., Heslop, H., Weitz, J., & Salama, M. E.

المصدر:  Hematology : Basic Principles and Practice

الجزء والصفحة:  8th E , P1006-1007

2026-10-27

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Therapy-related AML (t-AML) currently accounts for ∼10% to 20% of newly diagnosed AML, and its incidence is likely to rise in the future, given rising cancer survivorship. Post-remission therapy using conventional chemotherapy is usually not curative in secondary AML (s-AML: t-AML and AML arising from antecedent MDS or MPD) with the rare exception of CBF-AML, specifically inv(16) and t(15;17). Allogeneic HSCT is less effective in s-AML. The poorer survival appears multifactorial due to poor-risk cytogenetics and tumor-associated mutations (e.g., TP53, PPM1D), lower likelihood of entering remission, older patient age, and impaired organ function from prior cancer therapy; although some reports documented similar post-transplantation survival compared to de novo AML when adjusted for risk factors like disease status and cytogenetics. An observational analysis of 545 patients with t-AML identified risk factors influencing HSCT outcomes: age greater than 35 years, poor-risk cytogenetics, AML not in remission, and lack of well-matched donors. A prognostic score could stratify outcomes from 5-year OS of 50% (zero risk factors) to 4% (four risk factors).

Molecular genotyping offers insights into the clinical heterogeneity of s-AML. In a seminal analysis, Lindsley et al identified eight genes specifically mutated in s-AML (SRSF2, SF3B1, U2AF1, ZRSR2, SXL1, EZH2, BCOR, STAG2) that also identify worse prognosis “de novo” elderly AML, likely indicating undiagnosed ante cedent MDS. They also identified a molecular signature of “de novo” type AML. Finally, they confirmed that TP53, PPM1D mutations comprised a distinct set of AML with the worst outcomes. Molecular risk stratification offers the potential to redefine the clinical diagnosis of s-AML, refine AML risk prognostication, and potentially better select remission-inducing and post-remission therapy.