Homozygous HLA-C1 is Associated with Reduced Risk of Relapse after HLA-Matched Transplantation in Patients with Myeloid Leukemia

Nobuyoshi Arima, Junya Kanda, Junji Tanaka, Toshio Yabe, Yasuo Morishima, Sung Won Kim, Yuho Najima, Yukiyasu Ozawa, Tetsuya Eto, Heiwa Kanamori, Takehiko Mori, Naoki Kobayashi, Tadakazu Kondo, Hirohisa Nakamae, Naoyuki Uchida, Masami Inoue, Takahiro Fukuda, Tatsuo Ichinohe, Yoshiko Atsuta, Yoshinobu Kanda

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5 Citations (Scopus)

Abstract

Natural killer (NK) cells assume graft-versus-leukemia alloreactivity after hematopoietic stem cell transplantation (HSCT) through their inhibitory killer cell immunoglobulin-like receptors (KIRs). KIR2D family members recognize HLA-C alleles with Asn80 (HLA-C1) or Lys80 (HLA-C2). The predominance of HLA-C1 over HLA-C2 and the frequent presence of KIR2DL1 are characteristic of Japanese people. We compared clinical outcomes among homozygous HLA-C1 (HLA-C1/C1) patients and heterozygous HLA-C1/C2 patients who underwent HLA-matched HSCT for hematologic malignancies by assessing the data of 10,638 patients from the Japanese national registry. HLA-C1/C1 recipients had a lower rate of relapse than HLA-C1/C2 recipients after transplantation for acute myelogenous leukemia (AML) (hazard ratio [HR],.79; P =.006) and chronic myelogenous leukemia (CML) (HR,.48; P =.025), but not for acute lymphoblastic leukemia (HR, 1.36), lymphoma (HR,.97), or low-grade myelodysplastic syndrome (HR, 1.40). We then grouped AML and CML patients together and divided them into several subgroups. Advantages of HLA-C1/C1 recipients over HLA-C1/C2 recipients regarding relapse were observed irrespective of donor relation (related: HR,.79, P =.069; unrelated: HR,.77, P =.022), preparative regimen (myeloablative: HR,.79, P =.014; reduced intensity: HR,.73, P =.084), and occurrence of acute graft-versus-host disease (yes: HR,.70, P =.122; no, HR.71, P =.026) or cytomegalovirus reactivation (reactivated: HR.67,P =.054; nonreactivated: HR.71, P =.033); however, these advantages were not observed in recipients with a delay in achieving complete chimerism (HR, 1.06). The advantage of decreasing relapse and extending relapse-free survival of C1/1 over C1/2 KIR-ligand status was most pronounced in T cell-depleted HSCT (HR,.27; P <.001 and HR,.30; P =.002, respectively) and in children age <15 years (HR,.29; P <.001 and HR.31; P <.001, respectively). Our findings represent an important mechanism responsible for the immunity against HLA-C2–negative myeloid leukemia cells after HLA-matched transplantation.

Original languageEnglish
Pages (from-to)717-725
Number of pages9
JournalBiology of Blood and Marrow Transplantation
Volume24
Issue number4
DOIs
Publication statusPublished - 2018 Apr

Keywords

  • Allogeneic hematopoietic stem cell transplantation
  • Graft-versus-leukemia
  • HLA-C
  • Killer cell immunoglobulin-like receptor
  • Natural killer cell

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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    Arima, N., Kanda, J., Tanaka, J., Yabe, T., Morishima, Y., Kim, S. W., Najima, Y., Ozawa, Y., Eto, T., Kanamori, H., Mori, T., Kobayashi, N., Kondo, T., Nakamae, H., Uchida, N., Inoue, M., Fukuda, T., Ichinohe, T., Atsuta, Y., & Kanda, Y. (2018). Homozygous HLA-C1 is Associated with Reduced Risk of Relapse after HLA-Matched Transplantation in Patients with Myeloid Leukemia. Biology of Blood and Marrow Transplantation, 24(4), 717-725. https://doi.org/10.1016/j.bbmt.2017.11.029