Effect of Graft-versus-Host Disease on Post-Transplantation Outcomes following Single Cord Blood Transplantation Compared with Haploidentical Transplantation with Post-Transplantation Cyclophosphamide for Adult Acute Myeloid Leukemia

Takaaki Konuma; Kensuke Matsuda; Yoshimitsu Shimomura; Susumu Tanoue; Junichi Sugita; Yoshihiro Inamoto; Masahiro Hirayama; Takahide Ara; Hirohisa Nakamae; Shuichi Ota; Yumiko Maruyama; Tetsuya Eto; Naoyuki Uchida; Masatsugu Tanaka; Kazuya Ishiwata; Satoshi Koi; Satoshi Takahashi; Yukiyasu Ozawa; Makoto Onizuka; Yoshinobu Kanda; Takafumi Kimura; Tatsuo Ichinohe; Yoshiko Atsuta; Junya Kanda; Masamitsu Yanada

doi:10.1016/j.jtct.2023.03.001

Effect of Graft-versus-Host Disease on Post-Transplantation Outcomes following Single Cord Blood Transplantation Compared with Haploidentical Transplantation with Post-Transplantation Cyclophosphamide for Adult Acute Myeloid Leukemia

Transplant Cell Ther. 2023 Jun;29(6):365.e1-365.e11. doi: 10.1016/j.jtct.2023.03.001. Epub 2023 Mar 6.

Authors

Takaaki Konuma¹, Kensuke Matsuda², Yoshimitsu Shimomura³, Susumu Tanoue⁴, Junichi Sugita⁵, Yoshihiro Inamoto⁶, Masahiro Hirayama⁷, Takahide Ara⁸, Hirohisa Nakamae⁹, Shuichi Ota⁵, Yumiko Maruyama¹⁰, Tetsuya Eto¹¹, Naoyuki Uchida¹², Masatsugu Tanaka¹³, Kazuya Ishiwata¹⁴, Satoshi Koi¹⁵, Satoshi Takahashi¹⁶, Yukiyasu Ozawa¹⁷, Makoto Onizuka¹⁸, Yoshinobu Kanda¹⁹, Takafumi Kimura²⁰, Tatsuo Ichinohe²¹, Yoshiko Atsuta²², Junya Kanda²³, Masamitsu Yanada²⁴

Affiliations

¹ Department of Hematology and Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. Electronic address: tkonuma@ims.u-tokyo.ac.jp.
² Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
³ Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan.
⁴ Clinical Oncology and Hematology, The Jikei University School of Medicine, Tokyo, Japan.
⁵ Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan.
⁶ Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.
⁷ Department of Pediatrics, Mie University Graduate School of Medicine, Tsu, Japan.
⁸ Department of Hematology, Hokkaido University Hospital, Sapporo, Japan.
⁹ Hematology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan.
¹⁰ Department of Hematology, University of Tsukuba Hospital, Tsukuba, Japan.
¹¹ Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan.
¹² Department of Hematology, Toranomon Hospital, Tokyo, Japan.
¹³ Department of Hematology, Kanagawa Cancer Center, Yokohama, Japan.
¹⁴ Department of Hematology, Toranomon Hospital Kajigaya, Kanagawa, Japan.
¹⁵ Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
¹⁶ Division of Clinical Precision Research Platform, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
¹⁷ Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.
¹⁸ Department of Hematology and Oncology, Tokai University School of Medicine, Isehara, Japan.
¹⁹ Division of Hematology, Jichi Medical University, Tochigi, Japan.
²⁰ Preparation Department, Japanese Red Cross Kinki Block Blood Center, Osaka, Japan.
²¹ Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
²² Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan; Department of Registry Science for Transplant and Cellular Therapy, Aichi Medical University School of Medicine, Nagakute, Japan.
²³ Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
²⁴ Department of Hematology and Cell Therapy, Aichi Cancer Center, Nagoya, Japan.

PMID: 36889507
DOI: 10.1016/j.jtct.2023.03.001

Abstract

The possibility that HLA mismatches could reduce relapse after alternative HLA-mismatched allogeneic hematopoietic cell transplantation (HCT) is an attractive concept for treating acute myeloid leukemia (AML). However, it remains unclear whether the prognostic effect of graft-versus-host disease (GVHD) on survival differs between recipients of single-unit cord blood transplantation (CBT) and recipients of haploidentical HCT using post-transplantation cyclophosphamide (PTCy-haplo-HCT) for AML. The objective of this retrospective study was to compare the effect of acute GVHD and chronic GVHD on post-transplantation outcomes between recipients of CBT and recipients of PTCy-haplo-HCT. We retrospectively evaluated the effect of acute and chronic GVHD on post-transplantation outcomes following CBT and PTCy-haplo-HCT in adults with AML (n = 1981) between 2014 and 2020 using a Japanese registry database. In univariate analysis, the probability of overall survival was significantly greater in patients who developed grade I-II acute GVHD (P < .001, log-rank test) and limited chronic GVHD (P < .001, log-rank test) among CBT recipients, but these effects were not significant among PTCy-haplo-HCT recipients. In multivariate analysis, in which the development of GVHD was treated as a time-dependent covariate, the effect of grade I-II acute GVHD on reducing overall mortality differed significantly between CBT and PTCy-haplo-HCT (adjusted hazard ratio [HR] for CBT, .73, 95% confidence interval [CI], .60 to .87; adjusted HR for PTCy-haplo-HCT, 1.07; 95% CI, .70 to 1.64; P for interaction = .038). Our data demonstrate that grade I-II acute GVHD was associated with a significant improvement in overall mortality in adults with AML receiving CBT but not in recipients of PTCy-haplo-HCT.

Keywords: Acute myeloid leukemia; Cord blood transplantation; Graft-versus-host disease; Graft-versus-leukemia effect; Haploidentical transplantation; Posttransplant cyclophosphamide.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Cord Blood Stem Cell Transplantation*
Cyclophosphamide / therapeutic use
Graft vs Host Disease* / prevention & control
Hematopoietic Stem Cell Transplantation* / adverse effects
Humans
Leukemia, Myeloid, Acute* / therapy
Retrospective Studies
Transplantation, Haploidentical

Substances

Cyclophosphamide