Mild Acute Graft-Versus-Host Disease Improves Outcomes After HLA-Haploidentical-Related Donor Transplantation Using Posttransplant Cyclophosphamide and Cord Blood Transplantation

Author:

Wada Fumiya1ORCID,Kanda Junya1ORCID,Kamijo Kimimori2,Nishikubo Masashi2,Yoshioka Satoshi23,Ishikawa Takayuki2,Ueda Yasunori4,Akasaka Takashi5,Arai Yasuyuki1,Izumi Kiyotaka6,Hirata Hirokazu6,Ikeda Takashi7,Yonezawa Akihito8,Anzai Naoyuki9,Watanabe Mitsumasa10,Imada Kazunori3,Yago Kazuhiro11,Tamura Naoki12,Itoh Mitsuru12,Masuo Yuki13,Kunitomi Akane13,Takeoka Tomoharu13,Kitano Toshiyuki14,Arima Nobuyoshi15,Hishizawa Masakatsu16,Asagoe Kohsuke17,Kondo Tadakazu12,Takaori-Kondo Akifumi1

Affiliation:

1. Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

2. Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan

3. Department of Hematology, Japanese Red Cross Osaka Hospital, Osaka, Japan

4. Department of Hematology/Oncology, Kurashiki Central Hospital, Okayama, Japan

5. Department of Hematology, Tenri Hospital, Tenri, Japan

6. Department of Hematology, Kansai Electric Power Hospital, Osaka, Japan

7. Division of Hematology and Stem Cell Transplantation, Shizuoka Cancer Center, Shizuoka, Japan

8. Department of Hematology, Kokura Memorial Hospital, Fukuoka, Japan

9. Department of Hematology, Takatsuki Red Cross Hospital, Osaka, Japan

10. Department of Hematology, Hyogo Prefectural Amagasaki General Medical Center, Hyogo, Japan

11. Department of Hematology, Shizuoka General Hospital, Shizuoka, Japan

12. Department of Hematology, Kyoto City Hospital, Kyoto, Japan

13. Department of Hematology and Immunology, Japanese Red Cross Otsu Hospital, Shiga, Japan

14. Department of Hematology, Kitano Hospital, Osaka, Japan

15. Department of Hematology, Shinko Hospital, Hyogo, Japan

16. Department of Hematology, Kyoto-Katsura Hospital, Kyoto, Japan

17. Department of Hematology, Shiga General Hospital, Shiga, Japan

Abstract

Haploidentical-related donor transplantation using posttransplant cyclophosphamide (PTCy-haplo) and cord blood transplantation (CBT) are valid alternatives for patients with hematological malignancies when HLA-matched donor transplantation (MDT) is unavailable. However, the effects of graft-versus-host disease (GVHD) on outcomes after these transplants have not been fully elucidated. Therefore, we evaluated the effects of acute and chronic GVHD on transplant outcomes after PTCy-haplo transplants and compared them with CBT and MDT. We included a total of 914 adult patients with hematological malignancies in the Kyoto Stem Cell Transplantation Group registry who received PTCy-haplo (N = 120), CBT (N = 402), and MDT (N = 392), and achieved neutrophil engraftment. A multivariate analysis revealed that grade I–II acute GVHD improved of overall survival (OS) after PTCy-haplo [hazard ratio (HR) = 0.39, P = 0.018] and CBT (HR = 0.48, P < 0.001), but not after MDT (HR = 0.80, P = 0.267) compared with patients without acute GVHD. Grade I–II acute GVHD had a trend toward reducing the risk of nonrelapse mortality (NRM) after PTCy-haplo (HR = 0.13, P = 0.060) and this positive effect was significant after CBT (HR = 0.39, P = 0.003). A negative impact of grade III–IV acute GVHD on NRM was observed after CBT and MDT, but not after PTCy-haplo. Limited chronic GVHD had a positive impact on OS after CBT and MDT, but not after PTCy-haplo. In conclusion, mild acute GVHD improved outcomes after PTCy-haplo and CBT, and limited chronic GVHD improved outcomes after CBT and MDT. These data indicated that the effects of GVHD on transplant outcomes depended on transplant platforms.

Funder

Takeda Science Foundation

Japan Society for the Promotion of Science

Publisher

SAGE Publications

Subject

Transplantation,Cell Biology,Biomedical Engineering

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