Effects of HLA Allele and Killer Immunoglobulin-Like Receptor Ligand Matching on Clinical Outcome in Leukemia Patients Undergoing Transplantation With T-cell-Replete Marrow From an Unrelated Donor

Yasuo Morishima, Toshio Yabe, Keitaro Matsuo, Koichi Kashiwase, Hidetoshi Inoko, Hiroh Saji, Ken Yamamoto, Etsuko Maruya, Yoshiki Akatsuka, Makoto Onizuka, Hisashi Sakamaki, Hiroshi Sao, Seishi Ogawa, Shunichi Kato, Takeo Juji, Takehiko Sasazuki, Yoshihisa Kodera

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87 Citations (Scopus)

Abstract

The responsible human leukocyte antigen (HLA) locus and the role of killer immunoglobulin-like receptor (KIR) ligand matching on transplantation outcome were simultaneously identified by multivariate analysis in 1790 patients with leukemia who underwent transplantation with T-cell-replete marrow from an unrelated donor (UR-BMT) through the Japan Marrow Donor Program. The graft-versus-leukemia (GVL) effect depended on leukemia cell type. HLA-C mismatch reduced the relapse rate in acute lymphoblastic leukemia (ALL) (hazard ratio [HR] = 0.47; P = .003), and HLA-DPB1 mismatch reduced it in chronic myeloid leukemia (CML) (HR = 0.35; P < .001). In contrast, KIR2DL ligand mismatch in the graft-versus-host (GVH) direction (KIR-L-MM-G) increased in ALL (HR = 2.55; P = .017). An increased rejection rate was observed in KIR2DL ligand mismatch in the host-versus-graft direction (HR = 4.39; P = .012). Acute GVH disease (GVHD) was increased not only in the mismatch of HLA-A, -B, -C, and -DPB1, but also in KIR-L-MM-G. As a whole, the mismatch of HLA-A, -B, and -DQB1 locus and KIR-L-MM-G resulted in increased mortality. In conclusion, not only the mismatch of HLA-C and -DPB1, but also KIR-L-MM-G affected leukemia relapse, which should be considered based on leukemia cell type. Furthermore, KIR-L-MM induced adverse effects on acute GVHD (aGVHD) and rejection, and brought no survival benefits to patients with T-cell-replete UR-BMT.

Original languageEnglish
Pages (from-to)315-328
Number of pages14
JournalBiology of Blood and Marrow Transplantation
Volume13
Issue number3
DOIs
Publication statusPublished - 01-03-2007

All Science Journal Classification (ASJC) codes

  • Hematology
  • Transplantation

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    Morishima, Y., Yabe, T., Matsuo, K., Kashiwase, K., Inoko, H., Saji, H., Yamamoto, K., Maruya, E., Akatsuka, Y., Onizuka, M., Sakamaki, H., Sao, H., Ogawa, S., Kato, S., Juji, T., Sasazuki, T., & Kodera, Y. (2007). Effects of HLA Allele and Killer Immunoglobulin-Like Receptor Ligand Matching on Clinical Outcome in Leukemia Patients Undergoing Transplantation With T-cell-Replete Marrow From an Unrelated Donor. Biology of Blood and Marrow Transplantation, 13(3), 315-328. https://doi.org/10.1016/j.bbmt.2006.10.027