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

被引：1

作者：

Aribi, Ahmed ^{[1
]}

Salhotra, Amandeep ^{[1
]}

Afkhami, Michelle ^{[2
]}

Munteanu, Anamaria ^{[2
]}

Ali, Haris ^{[1
]}

Aldoss, Ibrahim ^{[1
]}

Otoukesh, Salman ^{[1
]}

Al Malki, Monzr M. ^{[1
]}

Sandhu, Karamjeet S. ^{[1
]}

Koller, Paul ^{[1
]}

Arslan, Shukaib ^{[1
]}

Stewart, Forrest ^{[1
]}

Artz, Andrew ^{[1
]}

Curtin, Peter ^{[1
]}

Ball, Brian ^{[1
]}

O'Hearn, James ^{[3
]}

Spielberger, Ricardo ^{[1
]}

Smith, Eileen ^{[1
]}

Budde, Elizabeth ^{[1
]}

Nakamura, Ryotaro ^{[1
]}

Stein, Anthony ^{[1
]}

Forman, Stephen ^{[1
]}

Marcucci, Guido ^{[1
]}

Becker, Pamela S. ^{[1
]}

Pullarkat, Vinod ^{[1
]}

机构：

[1] City Hope Natl Med Ctr, Dept Hematol, Duarte, CA 91010 USA

[2] City Hope Natl Med Ctr, Dept Pathol, Duarte, CA USA

[3] City Hope Natl Med Ctr, Dept Clin Translat Project Dev, Duarte, CA USA

来源：

LEUKEMIA & LYMPHOMA | 2023年 / 64卷 / 11期

关键词：

Acute myeloid leukemia; WT1; fludarabine; transplant; induction chemotherapy; WILMS-TUMOR GENE; PROGNOSTIC-SIGNIFICANCE; RESIDUAL DISEASE; WT1; MUTATIONS; EXPRESSION; THERAPY; ADULTS; RISK; AML;

D O I：

10.1080/10428194.2023.2241096

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：1811 / 1821

页数：11

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