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Allogeneic transplant for FLT3-ITD+ AML: room for improvement

Bone Marrow Transplantation volume 51, pages 508–510 (2016)Cite this article

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Fms-like tyrosine kinase 3 internal tandem duplication mutations (FLT3-ITD+) occur in 25% of newly diagnosed patients with AML. In patients younger than age 60 with normal karyotype AML, FLT3-ITD mutations consistently have been shown to be associated with high relapse rates and short time to relapse, particularly, in patients who receive chemotherapy alone as post-remission treatment. Remission rates after relapse are low and consequently survival is poor.1, 2 Accordingly, allogeneic transplantation has been employed in appropriate patients to attempt to mitigate the negative prognostic impact of FLT3-ITD mutation.

Whether allogeneic transplant for FLT3-ITD+ AML actually improves overall survival over traditional chemotherapy has not been specifically studied in a randomized prospective fashion. Instead, one must infer these results from a number of pediatric and younger adult AML trials, where AML patients in first remission with matched siblings received myeloablative transplants.3, 4, 5 Although initial results of donor versus no-donor analyses from these trials were conflicting and analyses complicated by low rates of transplant among patients with available donors, subsequent data with higher protocol adherence suggest rather substantial protection from relapse among FLT3-ITD+ patients. The magnitude of this benefit is sufficient to expect an improved survival from the approach and transplant is now an accepted frontline therapy for FLT3-ITD+ AML patients. Still, even within the FLT3-ITD+ population, relapse risk is variable. Although based upon a number of clinical and leukemia-specific factors, selection of optimal FLT3-ITD+ patients for transplant remains challenging. In this issue, Song and colleagues6 report addresses these questions; their report is both welcome and topical.

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Acknowledgements

This work was supported by the following grants from the National Cancer Institute 1K23CA141054-01 and R21 CA198621 to AEP.

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  1. Division of Hematology/Oncology, Abramson Cancer Center of the University of Pennsylvania, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    A E Perl & S M Luger

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Correspondence to A E Perl.

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AEP has served as a paid consultant to Astellas, Arog and Daiichi Sankyo/Ambit Biosciences. SML has received consulting fees and/or honoraria from Pfizer, Novartis, Karyopharm and Sigma Tau.

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Perl, A., Luger, S. Allogeneic transplant for FLT3-ITD+ AML: room for improvement. Bone Marrow Transplant 51, 508–510 (2016). https://doi.org/10.1038/bmt.2016.37

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