A randomized phase III study of pretransplant conditioning for AML/MDS with fludarabine and once daily IV busulfan ± clofarabine in allogeneic stem cell transplantation

被引：9

作者：

Andersson, Borje S. ^{[1
]}

Thall, Peter F. ^{[2
]}

Ma, Junsheng ^{[2
]}

Valdez, Benigno C. ^{[1
]}

Bassett, Roland, Jr. ^{[2
]}

Chen, Julianne ^{[1
]}

Ahmed, Sairah ^{[1
]}

Alousi, Amin ^{[1
]}

Bashir, Qaiser ^{[1
]}

Ciurea, Stefan ^{[1
]}

Gulbis, Alison ^{[3
]}

Cool, Rita ^{[3
]}

Kawedia, Jitesh ^{[3
]}

Hosing, Chitra ^{[1
]}

Kebriaei, Partow ^{[1
]}

Kornblau, Steve ^{[1
]}

Myers, Alan ^{[3
]}

Oran, Betul ^{[1
]}

Rezvani, Katayoun ^{[1
]}

Shah, Nina ^{[1
,4
]}

Shpall, Elizabeth ^{[1
]}

Parmar, Simrit ^{[1
]}

Popat, Uday R. ^{[1
]}

Nieto, Yago ^{[1
]}

Champlin, Richard E. ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Pharm, Houston, TX 77030 USA

[4] Univ Calif San Francisco, San Francisco, CA 94143 USA

来源：

BONE MARROW TRANSPLANTATION | 2022年 / 57卷 / 08期

关键词：

ACUTE MYELOID-LEUKEMIA; DAILY INTRAVENOUS BUSULFAN; VERSUS-HOST-DISEASE; VENOOCCLUSIVE DISEASE; AML; DIAGNOSIS; EXPOSURE; SURVIVAL; ADULTS; CYCLOPHOSPHAMIDE;

D O I：

10.1038/s41409-022-01705-7

中图分类号：

Q6 [生物物理学];

学科分类号：

071011 ;

摘要：

Pretransplant conditioning with Fludarabine (Flu)-Busulfan (Bu) is safe, but clofarabine (Clo) has improved antileukemic activity. Hypothesis: Flu+Clo-Bu (FCB) yields superior progression-free survival (PFS) after allogeneic transplantation. We randomized 250 AML/MDS patients aged 3-70, Karnofsky Score >= 80, with matched donors, to FCB (n = 120) or Flu-Bu (n = 130), stratifying complete remission (CR) vs. No CR, (NCR). HCT-CI scores varied, from 0 to 10. All evaluable patients engrafted. Median follow-up was 66 months (interquartile range: 58-80). Three-year relapse incidence (RI), 25% with FCB, vs. 39% with Flu-Bu (p = 0.018), offset by higher non-relapse mortality, 22.6% (95%CI: 16-30.2%) vs. 12.3% (95%CI: 6.5-19%). Three-year PFS was 52% (95%CI: 44-62%) (FCB), vs. 48% (95%CI: 41-58%) (Flu-Bu). FCB benefited CR patients less, NCR patients age <= 60 had 3-year 34% RI (95%CI: 19-49%) (FCB) vs. 56% (95%CI: 38-70%) after Flu-Bu (p = 0.037). NCR patients >60 years had 3-year RI 10.0% (FCB), vs. 56.0%, after Flu-Bu (p = 0.003). Bayesian regression analysis including treatment-covariate interactions showed FCB superiority in NCR patients with low HCT-CI (0-2). Serious adverse event profiles were similar for the regimens. Conditioning with FCB did not improve PFS overall, but improved disease control in NCR patients, mandating confirmatory trials. Remission status and HCT-CI should be considered when using FCB.

引用

页码：1295 / 1303

页数：9

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