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Feasibility of an intensified myeloablative conditioning regimen consisting of busulfan, fludarabine, cytarabine, and total body irradiation before single cord blood transplantation in elderly patients

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Abstract

The optimal conditioning regimen for stem cell transplantation in elderly patients remains to be established. We developed a novel preparative regimen using fludarabine 180 mg/m2, intravenous busulfan 12.8 mg/m2, cytarabine 8 g/m2, and 4-Gy total body irradiation before cord blood transplantation (CBT) in patients older than 55 years with various hematological malignancies. All but one patient received graft-versus-host disease (GVHD) prophylaxis consisting of cyclosporine (CsA) and short-term methotrexate (sMTX). Thirty-three patients were included in this study, with a median age of 64 years (range 56–70). The disease risk index was high or very high in 67% of patients, and 73% had a disease status other than complete remission. The probabilities of overall survival and disease-free survival at 3 years were 60 and 57%, respectively. The cumulative incidences of relapse and non-relapse mortality at 3 years were 18 and 25%, respectively. Regimen-related toxicities were generally tolerable. Disease-free survivors (n = 20) stopped immunosuppressants at a median of 7.4 months (range 2.6–25.0), in all cases by the time of the last follow-up. In conclusion, this highly myeloablative conditioning regimen resulted in a high probability of disease-free, GVHD-free, immunosuppressant-free survival after single CBT.

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Acknowledgments

I would like to express my sincere gratitude to Dr. Hiroaki Mitsuya for providing me this study opportunity in his laboratory. The authors thank all of the physicians, nurses, pharmacists, and other staff at the hospital for taking care of patients. The authors also thank the cord blood bank in Japan.

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Authors and Affiliations

  1. Department of Hematology, National Hospital Organization Kumamoto Medical Center, 1-5 Ninomaru, Chuo-ku, Kumamoto, 860-0008, Japan

    Toshiro Kawakita, Taichi Hirano, Yumiko Irie, Hironori Sugitani, Akira Kubota, Miho Watanabe, Mitsunori Ueno, Norikazu Mitsui, Shunichiro Yamaguchi, Yoshiko Inoue, Tatsunori Sakai, Naoko Harada & Michihiro Hidaka

  2. Departments of Hematology, Rheumatology, and Infectious Disease, Kumamoto Univerity Graduate School of Medicine, Kumamoto, Japan

    Toshiro Kawakita, Yoshitaka Inoue, Miho Watanabe, Mitsunori Ueno & Masao Matsuoka

  3. Department of Hematology, Arao Municipal Hospital, Kumamoto, Japan

    Shunichiro Yamaguchi

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  1. Toshiro Kawakita
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Contributions

TK designed the study, took care of patients, analyzed extracted data, and contributed to writing the paper; MH took care of patients, reviewed the study design, and contributed to writing the paper. YI and MM reviewed the study design and contributed to writing the paper; HS, MY, AK, TH, NM, SY, YI, TS, and NH took care of patients and contributed to writing the paper, and YI contributed to data coordination.

Corresponding author

Correspondence to Toshiro Kawakita.

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Conflict of Interest

Toshiro Kawakita reports personal fees from Otsuka Pharmaceutical, personal fees from Sanofi, outside the submitted work; Masao Matsuoka reports personal fees from Otsuka Pharmaceutical, personal fees from Sanofi, outside the submitted work. The other authors declare that they have no conflicts of interest.

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Kawakita, T., Hirano, T., Inoue, Y. et al. Feasibility of an intensified myeloablative conditioning regimen consisting of busulfan, fludarabine, cytarabine, and total body irradiation before single cord blood transplantation in elderly patients. Int J Hematol 114, 85–93 (2021). https://doi.org/10.1007/s12185-021-03131-9

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