Hematopoietic Stem Cell Transplantation for Relapsed, Refractory, and Induction-Failure 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
2026-10-27
96
Outcomes are typically poor for AML patients not in morphologic remission at the time of allogeneic HSCT, although the literature in this regard is limited, heterogeneous, and likely subject to patient selection and publication bias. A large analysis of MAC HSCT for acute leukemia in relapse or in primary induction failure (including 1673 AML patients) documented a 3-year OS of 19% in AML. On multivariable analysis, risk factors at time of HSCT of poor-risk cytogenetic AML, CR1 duration of less than 6 months, circulating AML blasts, performance score of less than 90%, and lack of an HLA-matched sibling donor predicted for 3-year survivals ranging between 42% (zero risk factors) and 6% (three or more risk factors). The major cause of death remains AML relapse, and innovative strategies to reduce leukemic burden before transplantation and enhance GVL effect after transplantation are likely required to improve survival of this extremely high-risk patient population.
In one instance for this patient population, the use of novel apoptosis-inducing agents (e.g., venetoclax) or agents targeting specific AML molecular pathways (e.g., FLT3, IDH 1/2, mTOR) with limited off-target toxicity as a bridge to allogeneic HSCT could offer important clinical benefit. In another instance, the use of novel adoptive cell therapies (e.g., cytokine-induced memory like NK cells) or graft-engineering approaches (e.g., αβ T cell- or regulatory T cell- [Treg] engineered grafts) to enhance GVL while controlling GVHD are important innovations under evaluation for high-risk leukemia. Finally, the ability to rapidly proceed to allogeneic transplantation may also be important given the dismal outcome of chemotherapy alone, suggesting a role for expeditious transplantation in this setting, especially for patients temporarily achieving a remission.
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