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
N1 - Funding Information:
Financial disclosure: This work was supported in part by a Grant-in-Aid from the Ministry of Health, Labour, and Welfare of Japan and by the Practical Research Project for Allergic Diseases and Immunology (Research Technology of Medical Transplantation) from the Japan Agency for Medical Research and Development (to Y.A.). The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
Publisher Copyright:
© 2017 The American Society for Blood and Marrow Transplantation
PY - 2018/4
Y1 - 2018/4
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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U2 - 10.1016/j.bbmt.2017.11.029
DO - 10.1016/j.bbmt.2017.11.029
M3 - Article
C2 - 29197675
AN - SCOPUS:85039974195
SN - 1083-8791
VL - 24
SP - 717
EP - 725
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 4
ER -