Abstract
Relapse is the main cause of mortality in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Adverse cytogenetic or molecular risk factors, as well as refractory disease or persistent measurable residual disease (MRD) at the time of transplantation are associated with an increased risk of recurrence. Salvage therapy for AML relapse after allo-HSCT is often limited to chemotherapy, donor lymphocyte infusions and/or second transplants and is rarely successful. Effective post-transplant preventive intervention in high risk AML may be crucial. The most frequent and promising approach is the use of post-transplant maintenance with hypomethylating agents or with FLT3 tyrosine kinase inhibitors when the target is present. Moreover, IDH1/IDH2 inhibitors and BCL-2 inhibitors in combination with other strategies are promising approaches in the maintenance setting. Here we summarize the current knowledge about the preemptive and prophylactic use of pharmacologic agents after allo-HSCT to prevent relapse of AML.
Highlights
Allogeneic hematopoietic stem cell transplantation is currently considered the optimal curative treatment option for patients with unfavorable risk acute myeloid leukemia (AML) [1,2,3]
The implementation of non-myeloablative conditioning regimens and the improvement in supportive care has led to decrease in the transplant-related mortality (TRM) and to significant increase in the number of transplant candidates, including older patients and/or those with comorbidities [4, 5]
Allo-HSCT is generally recommended when the benefit of relapse reduction outweighs the risk of non-relapse mortality (NRM)/morbidity and this is based on the assessment of cytogenetic and molecular genetic features as well as donor, patient, and transplant-related factors [7,8,9,10]
Summary
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently considered the optimal curative treatment option for patients with unfavorable risk acute myeloid leukemia (AML) [1,2,3]. Growing evidence strongly suggests that MRD detection by multiparametric flow cytometry (MFC), molecular techniques, or chimerism analyses after allo-HSCT may be used as a predictor of imminent relapse [41] These should be part of routine post-transplant follow-up since MRD detection can improve outcomes by guiding subsequent therapy aiming to unleash or enhance the GVL effect [39]. MRD by flow cytometry has many drawbacks including the lack of standardization, its lower sensitivity, the need for high technical expertise to differentiate between leukemic from regenerating bone marrow cells, biological heterogeneity of the leukemic population and the possibility of false negative results related to sample processing, hemodilution, number of events analyzed and immunophenotypic switch [45,46,47] Another method of MRD assessment is donor/recipient chimerism analysis that can detect host-derived hematopoiesis based on genomic differences between the recipient and the donor.
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