Allogeneic Hematopoietic Stem Cell Transplantation as a Platform to Treat Chemorefractory Acute Myeloid Leukemia in Adult Patients
Hematology and BMTU, Hospital of Bolzano (SABES–ASDAA), Teaching Hospital of Paracelsus Medical University (PMU), Via Lorenz Bohler 5, 39100 Bolzano, BZ, Italy
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Author to whom correspondence should be addressed.
Cancers 2025, 17(20), 3285; https://doi.org/10.3390/cancers17203285
Submission received: 24 August 2025
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Revised: 5 October 2025
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Accepted: 7 October 2025
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Published: 10 October 2025
(This article belongs to the Special Issue New Challenges in Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia)
Simple Summary
Results in the treatment of adult patients affected by chemorefractory acute myeloid leukemia are poor, with median survival around 2–4 months for patients ineligible for allogeneic hematopoietic stem cell transplantation and long-term survival in the order of 20–30% for those undergoing transplantation. It is widely debated how to make transplantation more effective. Increasing the dose-intensity by sequencing high-dose chemotherapy and reduced-intensity conditioning with transplantation performed during aplasia has been tested as a potential strategy, as well as other approaches centered on the optimization of alloreactivity of donor T- and NK-cells against host leukemia. This can be achieved by donor selection, accelerated withdrawal of immunosuppression, and the administration of donor lymphocyte infusion as prophylaxis or pre-emptive therapy of leukemia relapse. In this review, we will critically summarize the main tested strategies and address the yet unresolved issues.
Abstract
Adult patients affected by acute myeloid leukemia who fail to achieve remission after two cycles of intensive chemotherapy based on a combination of anthracyclines and cytarabine are considered chemorefractory and are unlikely to benefit from further induction attempts. Characterized by a poor prognosis, they may still benefit from allogeneic hematopoietic stem cell transplantation, even if long-term survival rarely exceeds 20–30%. Still, the use of sequential high-dose chemotherapy followed by reduced-intensity conditioning, with transplantation performed during aplasia, and the optimization of the alloreactivity of donor leukocytes against leukemia (i.e., the graft-versus-leukemia effect) may ameliorate these results. Optimization of alloreactivity against leukemic cells can be achieved by proper donor selection, by the early withdrawal of immunosuppressive therapy, by post-transplant administration of donor lymphocyte infusions as prophylaxis of leukemia relapse, and by several other maintenance and preemptive therapies. Far from being the final stage of consolidation therapy, allogeneic hematopoietic stem cell transplantation is now considered as the moment when a unique immunological platform can be established in these patients, to be used for additional post-transplant measures. In this study we will critically review the different pre- and post-transplant strategies used in clinical trials to improve long-term survival in adult patients transplanted with chemorefractory leukemia.
