Impact of human leucocyte antigen mismatch on graft-versus-host disease and graft failure after reduced intensity conditioning allogeneic haematopoietic stem cell transplantation from related donors

Takanori Teshima, Keitaro Matsuo, Kosei Matsue, Fumio Kawano, Shuichi Taniguchi, Masamichi Hara, Kazuo Hatanaka, Mitsune Tanimoto, Mine Harada, Shinji Nakao, Yasunobu Abe, Atsushi Wake, Tetsuya Eto, Yoshinobu Takemoto, Masahiro Imamura, Satoshi Takahashi, Yoji Ishida, Yoshinobu Kanda, Masaharu Kasai, Yoichi Takaue

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30 Citations (Scopus)

Abstract

The impact of human leucocyte antigen (HLA) incompatibility between donor and recipient on graft-versus-host disease (GVHD) and graft failure after reduced-intensity conditioning stem cell transplantation (RICT) remains to be elucidated. We retrospectively analysed outcome in 341 patients who underwent RICT from related donors for haematological malignancies. The overall cumulative incidence of grade II-IV acute GVHD (aGVHD) was 40% for all subjects; 39% in recipients with HLA-matched donors, 44% in those with one-locus-mismatched donors, and 50% in those with two- to three-loci-mismatched donors. In a Cox regression model adjusted for potential confounders, the tendency for grade II-IV aGVHD (P = 0·01), chronic GVHD (cGVHD) (P = 0·05) and graft failure (P = 0·033) increased with HLA disparity. Use of peripheral blood grafts instead of marrow was a risk factor for cGVHD. Use of antithymocyte globulin was associated with reduced aGVHD and cGVHD. Overall survival (OS) in recipients of two- to three-loci-mismatched RICT at 2 years (18%) was significantly worse than that in patients who received one-locus-mismatched RICT (51%) and HLA-matched RICT (48%) (P < 0·0001). A two- to three-loci mismatch was identified as an independent risk factor for OS (P < 0·001), but there was no significant difference in OS between HLA-matched and one-locus-mismatched RICT. HLA incompatibility between the donor and recipient is an important risk factor for graft failure, aGVHD, cGVHD and OS after RICT. RICT from a one-locus-mismatched donor may represent an effective alternative approach in patients with high-risk malignancies who lack HLA-matched related donors.

Original languageEnglish
Pages (from-to)575-587
Number of pages13
JournalBritish Journal of Haematology
Volume130
Issue number4
DOIs
Publication statusPublished - Aug 2005

Keywords

  • Antithymocyte globulin
  • Graft-versus-host disease
  • Human leucocyte antigen
  • Reduced intensity conditioning
  • Rejection

ASJC Scopus subject areas

  • Hematology

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  • Cite this

    Teshima, T., Matsuo, K., Matsue, K., Kawano, F., Taniguchi, S., Hara, M., Hatanaka, K., Tanimoto, M., Harada, M., Nakao, S., Abe, Y., Wake, A., Eto, T., Takemoto, Y., Imamura, M., Takahashi, S., Ishida, Y., Kanda, Y., Kasai, M., & Takaue, Y. (2005). Impact of human leucocyte antigen mismatch on graft-versus-host disease and graft failure after reduced intensity conditioning allogeneic haematopoietic stem cell transplantation from related donors. British Journal of Haematology, 130(4), 575-587. https://doi.org/10.1111/j.1365-2141.2005.05632.x