Favorable Outcome with Conditioning Regimen of Flu/Bu4/Mel in Acute Myeloid Leukemia Patients in Remission Undergoing Cord Blood Transplantation

Shohei Mizuno, Akiyoshi Takami, Koji Kawamura, Yoshimitsu Shimomura, Yasuyuki Arai, Takaaki Konuma, Yukiyasu Ozawa, Masashi Sawa, Shuichi Ota, Satoshi Takahashi, Naoyuki Anzai, Nobuhiro Hiramoto, Makoto Onizuka, Hirohisa Nakamae, Masatsugu Tanaka, Makoto Murata, Takafumi Kimura, Junya Kanda, Takahiro Fukuda, Yoshiko AtsutaMasamitsu Yanada

Research output: Contribution to journalArticlepeer-review

Abstract

Cord blood transplantation (CBT) is a curative therapeutic option for patients with acute myeloid leukemia (AML) who do not have an HLA-matched donor. The decline in early nonrelapse mortality (NRM) after CBT has significantly improved overall survival (OS) during the past 20 years because of advances in CBT practices, including more careful patient selection, use of safer conditioning regimens, better cord blood unit selection, and improved supportive care. A previous study reported a conditioning regimen comprising fludarabine, busulfan, and melphalan (Flu/Bu4/Mel) developed for patients undergoing CBT in non-complete remission (CR) myeloid malignancies that showed durable engraftment and remission with acceptable nonrelapse mortality (NRM), leading to excellent survival outcomes. However, no prior study has focused on the role of Flu/Bu4/Mel in CBT conditioning and compared it with conventional myeloablative conditioning (MAC) for AML patients in CR. We aimed to investigate the efficacy and safety of Flu/Bu4/Mel compared with cyclophosphamide and total body irradiation (CY/TBI)-based MAC for AML patients in CR who underwent CBT. Patients were selected from the Japanese nationwide transplantation registry according to the following inclusion criteria: (1) patients with AML aged ≥16 years, (2) first single-unit CBT, and (3) CR at the time of transplantation. Of 477 eligible patients, 148 (31.0%) received CY/TBI, 223 (46.8%) received high-dose cytarabine (HDCA)/CY/TBI, and 106 (22.2%) received Flu/Bu4/Mel. The probability of OS at 3 years was 64.8% (95% confidence interval [CI], 56.0% to 72.3%) in the CY/TBI group, 65.1% (95% CI, 57.8% to 71.4%) in the HDCA/CY/TBI group, and 65.5% (95% CI, 53.7% to 74.9%) in the Flu/Bu4/Mel group (P = .71); the cumulative incidence of relapse at 3 years was 22.0% (95% CI, 15.2% to 29.5%), 17.2% (95% CI, 12.2% to 22.9%), and 18.0% (95% CI, 11.2% to 26.2%), respectively (P = .40); and the cumulative incidence of NRM at 3 years was 17.2% (95% CI, 11.5% to 24.0%), 20.7% (95% CI, 15.4% to 26.7%), and 18.6% (95% CI, 11.4% to 27.2%), respectively (P = .95). Multivariate analysis identified Flu/Bu4/Mel as a favorable factor for OS; however, it was not significantly favorable for relapse and NRM in the CY/TBI, HDCA/CY/TBI, and Flu/Bu4/Mel groups (hazard ratio [HR],. 50 [95% CI,. 29-.88], P = .015;. 67 [95% CI,. 31-1.46], P = .31; and. 55 [95% CI,. 26-1.18], respectively; P = .12). Flu/Bu4/Mel was a favorable factor for neutrophil engraftment (HR, 1.51; 95% CI, 1.08 to 2.12; P = .016). Multivariate analysis showed that Flu/Bu4/Mel had a favorable prognostic impact on OS and neutrophil engraftment despite the non-TBI regimen. Our findings suggest that Flu/Bu4/Mel may sustain the antileukemia effect with decreasing NRM and could be a favorable CBT conditioning regimen for patients with AML in CR.

Original languageEnglish
Pages (from-to)775.e1-775.e9
JournalTransplantation and Cellular Therapy
Volume28
Issue number11
DOIs
StatePublished - Nov 2022
Externally publishedYes

Keywords

  • Acute myeloid leukemia
  • Complete remission
  • Cord blood transplantation
  • Intravenous busulfan
  • Melphalan
  • Myeloablative conditioning

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