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

Research output: Contribution to journalArticle

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
JournalBiology of Blood and Marrow Transplantation
DOIs
Publication statusAccepted/In press - 2018 Jan 1

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Myeloid Leukemia
Hematopoietic Stem Cell Transplantation
Transplantation
KIR Receptors
Recurrence
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Acute Myeloid Leukemia
HLA-C Antigens
Chimerism
Myelodysplastic Syndromes
Graft vs Host Disease
Hematologic Neoplasms
Myeloid Cells
Cytomegalovirus
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Natural Killer Cells
Registries
Immunity
Lymphoma
Leukemia

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

Cite this

Homozygous HLA-C1 is Associated with Reduced Risk of Relapse after HLA-Matched Transplantation in Patients with Myeloid Leukemia. / Arima, Nobuyoshi; Kanda, Junya; Tanaka, Junji; Yabe, Toshio; Morishima, Yasuo; Kim, Sung Won; Najima, Yuho; Ozawa, Yukiyasu; Eto, Tetsuya; Kanamori, Heiwa; Mori, Takehiko; Kobayashi, Naoki; Kondo, Tadakazu; Nakamae, Hirohisa; Uchida, Naoyuki; Inoue, Masami; Fukuda, Takahiro; Ichinohe, Tatsuo; Atsuta, Yoshiko; Kanda, Yoshinobu.

In: Biology of Blood and Marrow Transplantation, 01.01.2018.

Research output: Contribution to journalArticle

Arima, N, Kanda, J, Tanaka, J, Yabe, T, Morishima, Y, Kim, SW, 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. https://doi.org/10.1016/j.bbmt.2017.11.029
Arima, Nobuyoshi ; Kanda, Junya ; Tanaka, Junji ; Yabe, Toshio ; Morishima, Yasuo ; Kim, Sung Won ; Najima, Yuho ; Ozawa, Yukiyasu ; Eto, Tetsuya ; Kanamori, Heiwa ; Mori, Takehiko ; Kobayashi, Naoki ; Kondo, Tadakazu ; Nakamae, Hirohisa ; Uchida, Naoyuki ; Inoue, Masami ; Fukuda, Takahiro ; Ichinohe, Tatsuo ; Atsuta, Yoshiko ; Kanda, Yoshinobu. / Homozygous HLA-C1 is Associated with Reduced Risk of Relapse after HLA-Matched Transplantation in Patients with Myeloid Leukemia. In: Biology of Blood and Marrow Transplantation. 2018.
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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.",
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TY - JOUR

T1 - Homozygous HLA-C1 is Associated with Reduced Risk of Relapse after HLA-Matched Transplantation in Patients with Myeloid Leukemia

AU - Arima, Nobuyoshi

AU - Kanda, Junya

AU - Tanaka, Junji

AU - Yabe, Toshio

AU - Morishima, Yasuo

AU - Kim, Sung Won

AU - Najima, Yuho

AU - Ozawa, Yukiyasu

AU - Eto, Tetsuya

AU - Kanamori, Heiwa

AU - Mori, Takehiko

AU - Kobayashi, Naoki

AU - Kondo, Tadakazu

AU - Nakamae, Hirohisa

AU - Uchida, Naoyuki

AU - Inoue, Masami

AU - Fukuda, Takahiro

AU - Ichinohe, Tatsuo

AU - Atsuta, Yoshiko

AU - Kanda, Yoshinobu

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - Allogeneic hematopoietic stem cell transplantation

KW - Graft-versus-leukemia

KW - HLA-C

KW - Killer cell immunoglobulin-like receptor

KW - Natural killer cell

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