Influence of HLA 1–3-locus mismatch and antithymocyte globulin administration in unrelated bone marrow transplantation

Koji Kawamura, Junya Kanda, Kazuteru Ohashi, Takahiro Fukuda, Koji Iwato, Tetsuya Eto, Shin ichiro Fujiwara, Takehiko Mori, Kentaro Fukushima, Yukiyasu Ozawa, Naoyuki Uchida, Takashi Ashida, Tatsuo Ichinohe, Yoshiko Atsuta, Yoshinobu Kanda

Research output: Contribution to journalArticle

Abstract

For patients without an HLA-matched donor, an HLA-mismatched unrelated donor (MMUD) has been considered as an alternative donor in allogeneic hematopoietic cell transplantation (allo-HCT). We conducted a nationwide retrospective study to compare the transplant outcomes among 1-, 2-, and 3-locus (allele/antigen) mismatched unrelated donors (1MMUD n = 2044, 2MMUD n = 492, and 3MMUD n = 73) in allo-HCT and to assess the impact of antithymocyte globulin (ATG) in allo-HCT from 1-3MMUD. 2MMUD and 3MMUD were independent significant adverse factors for grade III–IV acute graft-versus-host disease (GVHD) (hazard ratio [HR] 1.72, p < 0.001 and HR 2.48, p < 0.001), non-relapse mortality (NRM) (HR 1.47, p < 0.001 and HR 2.00, p < 0.001), and overall survival (OS) (HR 1.21, p = 0.0066 and HR 1.60, p = 0.0015). Conversely, the use of ATG was an independent favorable factor for grade III–IV acute GVHD (HR 0.43, p < 0.001), NRM (HR 0.51, p < 0.001), and OS (HR 0.74, p = 0.0012). On the other hand, HLA compatibility and the use of ATG were not associated with a risk of relapse. An interaction test between the number of HLA mismatches and the use of ATG revealed that the effect of ATG on NRM and OS in the 2MMUD group was significantly less than that in the 1MMUD group (HR 1.53, p = 0.036 and HR 2.34, p = 0.0046). This study indicated that the number of HLA mismatches and the use of ATG were significantly associated with not only GVHD, but also NRM and OS. Whereas the use of ATG could improve transplant outcomes in allo-HCT from 1MMUD, its effectiveness with 2MMUD and 3MMUD was limited.

Original languageEnglish
Pages (from-to)1099-1110
Number of pages12
JournalAnnals of Hematology
Volume99
Issue number5
DOIs
Publication statusPublished - 2020 May 1

Keywords

  • Antithymocyte globulin
  • Bone marrow transplantation
  • Graft-versus-host disease
  • HLA-mismatched unrelated donor

ASJC Scopus subject areas

  • Hematology

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  • Cite this

    Kawamura, K., Kanda, J., Ohashi, K., Fukuda, T., Iwato, K., Eto, T., Fujiwara, S. I., Mori, T., Fukushima, K., Ozawa, Y., Uchida, N., Ashida, T., Ichinohe, T., Atsuta, Y., & Kanda, Y. (2020). Influence of HLA 1–3-locus mismatch and antithymocyte globulin administration in unrelated bone marrow transplantation. Annals of Hematology, 99(5), 1099-1110. https://doi.org/10.1007/s00277-020-03995-7