Effect of Conditioning Regimens and Graft-versus-Host Disease Prophylaxis on the Outcomes of Umbilical Cord Blood Transplantation Performed with Cyclophosphamide/Total Body Irradiation-Based Regimens

Nobuhiko Imahashi; Naoki Kurita; Takaaki Konuma; Satoshi Takahashi; Tetsuya Nishida; Masatsugu Tanaka; Hirohisa Nakamae; Toshiro Kawakita; Shuichi Ota; Noriko Doki; Yasushi Onishi; Masashi Sawa; Kazutaka Ozeki; Nobuhiro Hiramoto; Makoto Onizuka; Fumihiko Ishimaru; Tatsuo Ichinohe; Yoshiko Atsuta; Junya Kanda

doi:10.1016/j.jtct.2023.12.004

Effect of Conditioning Regimens and Graft-versus-Host Disease Prophylaxis on the Outcomes of Umbilical Cord Blood Transplantation Performed with Cyclophosphamide/Total Body Irradiation-Based Regimens

Transplant Cell Ther. 2024 Mar;30(3):318.e1-318.e11. doi: 10.1016/j.jtct.2023.12.004. Epub 2023 Dec 9.

Authors

Nobuhiko Imahashi¹, Naoki Kurita², Takaaki Konuma³, Satoshi Takahashi³, Tetsuya Nishida⁴, Masatsugu Tanaka⁵, Hirohisa Nakamae⁶, Toshiro Kawakita⁷, Shuichi Ota⁸, Noriko Doki⁹, Yasushi Onishi¹⁰, Masashi Sawa¹¹, Kazutaka Ozeki¹², Nobuhiro Hiramoto¹³, Makoto Onizuka¹⁴, Fumihiko Ishimaru¹⁵, Tatsuo Ichinohe¹⁶, Yoshiko Atsuta¹⁷, Junya Kanda¹⁸

Affiliations

¹ Department of Hematology, National Hospital Organization Nagoya Medical Center, Nagoya, Japan. Electronic address: nimahashi@med.nagoya-u.ac.jp.
² Department of Hematology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
³ Department of Hematology/Oncology, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
⁴ Department of Hematology, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital, Nagoya, Japan.
⁵ Department of Hematology, Kanagawa Cancer Center, Yokohama, Japan.
⁶ Department of Hematology, Osaka Metropolitan University Hospital, Osaka, Japan.
⁷ Department of Hematology, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan.
⁸ Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan.
⁹ Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
¹⁰ Department of Hematology, Tohoku University Hospital, Sendai, Japan.
¹¹ Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan.
¹² Department of Hematology and Oncology, Konan Kosei Hospital, Konan, Japan.
¹³ Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan.
¹⁴ Department of Hematology/Oncology, Tokai University School of Medicine, Isehara, Japan.
¹⁵ Japanese Red Cross Kanto-Koshinetsu Block Blood Center, Tokyo, Japan.
¹⁶ Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
¹⁷ Japanese Data Center for Hematopoietic Cell Transplantation, Nagakute, Japan; Department of Registry Science for Transplant and Cellular Therapy, Aichi Medical University School of Medicine, Nagakute, Japan.
¹⁸ Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

PMID: 38081416
DOI: 10.1016/j.jtct.2023.12.004

Abstract

Umbilical cord blood (UCB) is a valuable alternative donor source for allogeneic hematopoietic stem cell transplantation. Various conditioning regimens and graft-versus-host disease (GVHD) prophylaxis regimens aimed at improving the outcomes of umbilical cord blood transplantation (UCBT) have been explored; however, the differences in their effects remain unclear. This study was conducted to elucidate the differences in the effects of conditioning and GVHD prophylaxis regimens on UCBT outcomes by disease type in a nationwide, retrospective study. We retrospectively analyzed the effects of conditioning and GVHD prophylaxis regimens on the outcomes of UCBT performed with cyclophosphamide (Cy)/total body irradiation (TBI)-based regimens in patients with acute myeloid leukemia (AML; n = 1126), acute lymphoblastic leukemia (ALL; n = 620), myelodysplastic syndrome (MDS; n = 170), and lymphoma (n = 128). Multivariate analysis for overall survival (OS) demonstrated the benefit of adding high-dose cytarabine to the Cy/TBI regimen for the AML group (relative risk [RR], .76; P = .003) and lymphoma group (RR, .54; P = .02), but not for the ALL and MDS groups. In the ALL group, adding etoposide to the Cy/TBI regimen was associated with a lower OS (RR, 1.45; P = .03). For GVHD prophylaxis, a tacrolimus/methotrexate regimen was associated with a lower OS compared with a cyclosporine/methotrexate regimen in the AML group (RR, 1.26; P = .01); this difference was not observed in the other groups. These differences in OS according to the conditioning and GVHD prophylaxis regimen were attributable mainly to differences in relapse risk. Our data show that the effects of conditioning regimens and GVHD prophylaxis on UCBT outcomes differed according to disease type. UCBT outcomes could be improved by selecting optimal conditioning regimens and GVHD prophylaxis for each disease type.

Keywords: Conditioning regimen; GVHD prophylaxis; Myeloablative conditioning regimen; Umbilical cord blood transplantation.

MeSH terms

Cord Blood Stem Cell Transplantation*
Cyclophosphamide / therapeutic use
Disease-Free Survival
Graft vs Host Disease* / drug therapy
Graft vs Host Disease* / prevention & control
Hematopoietic Stem Cell Transplantation* / adverse effects
Humans
Leukemia, Myeloid, Acute* / drug therapy
Lymphoma* / drug therapy
Methotrexate / therapeutic use
Retrospective Studies
Whole-Body Irradiation

Substances

Cyclophosphamide
Methotrexate