Advantages of Higher Busulfan Dose Intensity in Fludarabine-Combined Conditioning for Patients with Acute Myeloid Leukemia Undergoing Cord Blood Transplantation.

Abstract

The alkylating agent busulfan is commonly used as conditioning in allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia (AML). However, a consensus has not yet been reached regarding the optimal busulfan dose in cord blood transplantation (CBT). Therefore, we conducted this large nationwide cohort study to retrospectively analyze the outcomes of CBT in patients with AML receiving busulfan at intermediate (6.4 mg/kg i.v.; BU2) or higher (12.8 mg/kg i.v.; BU4) doses within a fludarabine/i.v. busulfan (FLU/BU) regimen. Among 475 patients who underwent their first CBT following FLU/BU conditioning between 2007 and 2018, 162 received BU2 and 313 received BU4. Multivariate analysis identified BU4 as a significant factor for longer disease-free survival (hazard ratio [HR], .85; 95% confidence interval [CI], .75 to .97; P = .014) and a lower relapse rate (HR, .84; 95% CI, .72 to .98; P = .030). No significant differences were observed in non-relapse mortality between BU4 and BU2 (HR, 1.05; 95% CI, .88-1.26; P = .57). Subgroup analyses showed that BU4 provided significant benefits for patients who underwent transplantation while not in complete remission (CR) and those age <60 years. Our present results suggest that higher busulfan doses are preferable in patients undergoing CBT, particularly those not in CR and younger patients.

• Authors: Sho Shibata, Yasuyuki Arai, Tadakazu Kondo, Shohei Mizuno, Kaito Harada, Shigesaburo Miyakoshi, Naoyuki Uchida, Yumiko Maruyama, Tetsuya Eto, Yuna Katsuoka, Kosei Matsue, Kaichi Nishiwaki, Satoru Takada, Noriko Doki, Mitsuru Itoh, Koji Nagafuji, Toshiro Kawakita, Junji Tanaka, Takahiro Fukuda, Yoshiko Atsuta, Masamitsu Yanada
• Journal: Transplantation and cellular therapy (Transplant Cell Ther) Vol. 29 Issue 5 Pg. 332.e1-332.e11 (05 2023) ISSN: 2666-6367 [Electronic] United States
• PMID: 36796517 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Chemical References

• Busulfan
• fludarabine

Topics

• Humans
• Middle Aged
• Busulfan (therapeutic use)
• Cohort Studies
• Retrospective Studies
• Cord Blood Stem Cell Transplantation
• Hematopoietic Stem Cell Transplantation (methods)
• Leukemia, Myeloid, Acute (therapy)
• Recurrence