WT1-mutated acute myeloid leukemia is sensitive to fludarabine-based chemotherapy and conditioning regimens

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.

Keywords:

• Acute myeloid leukemia
• WT1
• fludarabine
• transplant
• induction chemotherapy

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

All data have been published within the contents of this publication.

Additional information

Funding

This pilot trial was funded by the intramural Chairs Discretionary grant and NIH grants P30 CA033572 and (others).