1. WT1 -mutated acute myeloid leukemia is sensitive to fludarabine-based chemotherapy and conditioning regimens.
- Author
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Aribi A, Salhotra A, Afkhami M, Munteanu A, Ali H, Aldoss I, Otoukesh S, Al Malki MM, Sandhu KS, Koller P, Arslan S, Stewart F, Artz A, Curtin P, Ball B, O'Hearn J, Spielberger R, Smith E, Budde E, Nakamura R, Stein A, Forman S, Marcucci G, Becker PS, and Pullarkat V
- Subjects
- Humans, Retrospective Studies, Antineoplastic Combined Chemotherapy Protocols adverse effects, Idarubicin therapeutic use, Cytarabine therapeutic use, WT1 Proteins genetics, Melphalan therapeutic use, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute genetics
- Abstract
We conducted a retrospective analysis of WT1- mutated acute myeloid leukemia (AML) patients who underwent allogeneic stem cell transplant. Thirty-seven patients with WT1- mutated AML were identified. Primary induction failure (40%) and early relapse rate (18%) after idarubicin/cytarabine (7 + 3) chemotherapy were observed. All patients with induction failure subsequently achieved CR with additional chemotherapy. There was no significant difference between outcomes after myeloablative vs. reduced intensity (Fludarabine/Melphalan [Flu/Mel]) conditioning regimens. RFS but not OS was significantly better in patients who received FLAG-IDA prior to transplant and/or a fludarabine-containing conditioning. In an independent ex vivo study, WT1 -mutated AML samples exhibited greater sensitivity to fludarabine ( p = 0.026) and melphalan ( p = 0.0005) than non- WT1- mutated AML samples while there was no difference between sensitivity to cytarabine. Our data favor using a fludarabine-based induction for AML with WT1 mutation instead of 7 + 3. Fludarabine conditioning regimens for alloHCT showed better RFS but not OS.
- Published
- 2023
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