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Dasatinib maintenance following allogeneic transplantation in acute myeloid leukemia with KIT mutation

Bone Marrow Transplantation volume 60, pages 83–85 (2025)Cite this article

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Core binding factor acute myeloid leukemia (AML) defined by cytogenetic abnormalities of t(8;21)(q22;q22) and inv(16)(p13q22)/t(16;16)(p13;q22) [referred to as t(8;21) and inv(16) respectively] is classified as favorable risk by the ELN 2022 guidelines in the context of cytarabine-based intensive chemotherapy [1]. Harboring either of these aberrations results in the formation of fusion genes, RUNX1-RUNX1T1 (or AML1/ETO) and CBFB-MYH11 respectively, that disrupt the function of core-binding factor (CBF) necessary for normal hematopoiesis [2]. Studies have shown complete remission (CR) rates of approximately 80–90% in adult CBF AML and allogeneic hematopoietic stem cell transplantation (alloHCT) is generally not recommended in first remission (CR1). Unfortunately, approximately 40–50% will eventually experience a relapse [3].

The impact of concomitant mutations with CBF AML on outcomes has been of interest to refine prognostication. In particular, the presence of KIT mutations, found in approximately 25% of CBF AML patients, have been associated with higher relapse rates [4, 5]. Marcucci et al. published their results that demonstrated that the addition of Dasatinib, a multi-kinase inhibitor with activity to KIT and SRC, to 7 + 3 and high-dose cytarabine consolidation yielded a CR rate of 90% with only a relapse rate of 16% in all patients with CBF AML [4]. In addition, the study produced 3-year disease free survival (DFS) and overall survival (OS) results of 75% and 77% respectively, with much better responses seen in younger patients with an age less than 60 years (79% and 85% for younger patients, and 60% and 51% for older patients). KIT mutation was present in 11 out of 60 patients (19%) and was only able to show benefit in younger patients only when compared to wild-type in a post-hoc analysis with a 3-yr DFS of 83% in KIT mutated compared to 77% KIT wild-type and 3-yr OS of 88% in KIT mutated compared to 84% in KIT wild-type. The authors reported that alloHCT was performed in six patients (one in CR1 and 5 with relapse), but outcomes for these patients were not described. In patients who do experience a relapse or have rising measurable residual disease (MRD) in CR1, HCT is indicated.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Author notes

  1. These authors contributed equally: Dat Ngo, Amanda Blackmon

Authors and Affiliations

  1. Department of Pharmacy, City of Hope, Duarte, CA, USA

    Dat Ngo

  2. Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA

    Amanda Blackmon & Monzr M. Al Malki

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  1. Dat Ngo
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  2. Amanda Blackmon
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  3. Monzr M. Al Malki
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DN was responsible for data extracting and reporting, preparation of manuscript. AB and MAL were responsible for concept design and editing of manuscript.

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Correspondence to Dat Ngo.

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Ngo, D., Blackmon, A. & Al Malki, M.M. Dasatinib maintenance following allogeneic transplantation in acute myeloid leukemia with KIT mutation. Bone Marrow Transplant 60, 83–85 (2025). https://doi.org/10.1038/s41409-024-02425-w

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