Altered effect of killer immunoglobulin-like receptor–ligand mismatch by graft versus host disease prophylaxis in cord blood transplantation

Hisayuki Yokoyama, Masahiro Hirayama, Yoshiyuki Takahashi, Naoyuki Uchida, Masatsugu Tanaka, Makoto Onizuka, Yukiyasu Ozawa, Daishi Onai, Yuna Katsuoka, Atsushi Wake, Masashi Sawa, Hikaru Kobayashi, Yumiko Maruyama, Kazutaka Ozeki, Takafumi Kimura, Junya Kanda, Takahiro Fukuda, Yoshiko Atsuta, Seitaro Terakura, Satoko Morishima

Research output: Contribution to journalArticlepeer-review

Abstract

The role of killer immunoglobulin-like receptor–ligand mismatch (KIR–ligand mismatch) between donors and recipients undergoing cord blood transplantation (CBT) is controversial. If each immunosuppressant differently affects natural killer (NK) cell function, the effect of KIR–ligand mismatch may be altered depending on the type of graft versus host disease (GVHD) prophylaxis. To verify this hypothesis, the difference in the effect of KIR–ligand mismatch was retrospectively assessed between patients who received CBT for acute leukemia, myelodysplastic syndrome, or chronic myeloid leukemia, as well as GVHD prophylaxis comprising tacrolimus plus methotrexate (MTX) or mycophenolate mofetil (MMF). In the MMF group (n = 1363), KIR–ligand mismatch augmented the incidence of non-relapse mortality (NRM; hazard ratio [HR], 1.40; P = 0.008), which worsened overall survival (OS; HR, 1.30, P = 0.0077). In the analysis of each KIR–ligand mismatch type, HLA-C2 mismatch had a favorable effect on relapse incidence (HR, 0.56; P = 0.0043) and OS (HR, 0.72; P = 0.037) only in the MTX group. In the MMF group, HLA-A3/A11 mismatch worsened NRM (HR, 1.93; P < 0.001) and OS (HR, 1.48; P = 0.014). These results imply that the effects of KIR–ligand mismatch differ with the type of GVHD prophylaxis and that assessing the KIR–ligand mismatch status is important for CBT.

Original languageEnglish
JournalBone Marrow Transplantation
DOIs
Publication statusAccepted/In press - 2021
Externally publishedYes

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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