Improved outcomes of single-unit cord blood transplantation for acute myeloid leukemia by killer immunoglobulin-like receptor 2DL1-ligand mismatch

Hisayuki Yokoyama; Minoru Kanaya; Tomoki Iemura; Masahiro Hirayama; Satoshi Yamasaki; Tadakazu Kondo; Naoyuki Uchida; Satoshi Takahashi; Masatsugu Tanaka; Makoto Onizuka; Yukiyasu Ozawa; Yasuji Kozai; Tetsuya Eto; Yasuhiro Sugio; Atsushi Hamamura; Toshiro Kawakita; Nobuyuki Aotsuka; Satoru Takada; Atsushi Wake; Takafumi Kimura; Tatsuo Ichinohe; Yoshiko Atsuta; Masamitsu Yanada; Satoko Morishima

doi:10.1038/s41409-022-01700-y

Improved outcomes of single-unit cord blood transplantation for acute myeloid leukemia by killer immunoglobulin-like receptor 2DL1-ligand mismatch

Bone Marrow Transplant. 2022 Jul;57(7):1171-1179. doi: 10.1038/s41409-022-01700-y. Epub 2022 May 10.

Authors

Hisayuki Yokoyama¹, Minoru Kanaya², Tomoki Iemura³, Masahiro Hirayama⁴, Satoshi Yamasaki⁵, Tadakazu Kondo³, Naoyuki Uchida⁶, Satoshi Takahashi⁷, Masatsugu Tanaka⁸, Makoto Onizuka⁹, Yukiyasu Ozawa¹⁰, Yasuji Kozai¹¹, Tetsuya Eto¹², Yasuhiro Sugio¹³, Atsushi Hamamura¹⁴, Toshiro Kawakita¹⁵, Nobuyuki Aotsuka¹⁶, Satoru Takada¹⁷, Atsushi Wake¹⁸, Takafumi Kimura¹⁹, Tatsuo Ichinohe²⁰, Yoshiko Atsuta^{21

22}, Masamitsu Yanada²³, Satoko Morishima²⁴

Affiliations

¹ Department of Hematology, Tohoku University Graduate School of Medicine, Sendai, Japan. hisayuki.yokoyama.a1@tohoku.ac.jp.
² Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
³ Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
⁴ Department of Pediatrics, Mie University Graduate School of Medicine, Tsu, Japan.
⁵ Department of Internal Medicine, Kyushu University Beppu Hospital, Beppu, Japan.
⁶ Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital, Tokyo, Japan.
⁷ Division of Clinical Precision Research Platform, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
⁸ Department of Hematology, Kanagawa Cancer Center, Yokohama, Japan.
⁹ Department of Hematology/Oncology, Tokai University School of Medicine, Isehara, Japan.
¹⁰ Department of Hematology, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital, Nagoya, Japan.
¹¹ Department of Transfusion Medicine, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan.
¹² Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan.
¹³ Department of Hematology, Kitakyushu City Hospital Organization, Kitakyushu Municipal Medical Center, Kitakyushu, Japan.
¹⁴ Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
¹⁵ Department of Hematology, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan.
¹⁶ Division of Hematology-Oncology, Japanese Red Cross Society Narita Hospital, Narita, Japan.
¹⁷ Leukemia Research Center, Saiseikai Maebashi Hospital, Maebashi, Japan.
¹⁸ Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations, Toranomon Hospital, Kajigaya, Japan.
¹⁹ Preparation Department, Japanese Red Cross Kinki Block Blood Center, Ibaraki, Japan.
²⁰ Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
²¹ Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan.
²² Department of Registry Science for Transplant and Cellular Therapy, Aichi Medical University School of Medicine, Nagoya, Japan.
²³ Department of Hematology and Cell Therapy, Aichi Cancer Center, Nagoya, Japan.
²⁴ Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine), Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan.

PMID: 35538140
DOI: 10.1038/s41409-022-01700-y

Abstract

The impact of the killer immunoglobulin-like receptor (KIR)-ligand mismatch between donor and recipient in hematopoietic stem cell transplantation is controversial. Recently, it has been suggested that their effect on cord blood transplantation (CBT) differs among types of mismatched KIR-ligand and graft-versus-host disease (GVHD) prophylaxis. To investigate their role in acute myeloid leukemia (AML), mismatch of KIR2DL1, KIR3DL1, and KIR3DL2-ligand (HLA-C2, Bw4, and A3/11) were retrospectively assessed in patients undergoing CBT with GVHD prophylaxis comprising a calcineurin inhibitor plus methotrexate (CNI/MTX) or mycophenolate mofetil (CNI/MMF). In patients who received CNI/MTX, a favorable effect of KIR-ligand mismatch on relapse was noted in HLA-C2 mismatched cases (24.8% at 3 years post-CBT [no HLA-C2 mismatch, n = 1602] vs. 15.4% [HLA-C2 mismatch, n = 161], P = 0.0116). In this group, overall survival (OS) was also superior (68.2%, P = 0.0083) compared to the other group (55.0%). Multivariate analysis results supported these findings (hazard ratio [HR] 0.61 for relapse, P = 0.017 and HR 0.72 for OS, P = 0.016). However, the KIR-ligand mismatch effect was not observed in patients with KIR-ligand mismatch types other than HLA-C2 and those using CNI/MMF for GVHD prophylaxis. These results suggest that HLA-C2 mismatch in CBT using CNI/MTX as GVHD prophylaxis may improve the outcomes of patients with AML.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Calcineurin Inhibitors
Cord Blood Stem Cell Transplantation* / methods
Graft vs Host Disease* / prevention & control
Hematopoietic Stem Cell Transplantation*
Humans
Leukemia, Myeloid, Acute* / therapy
Ligands
Methotrexate
Mycophenolic Acid
Receptors, KIR
Recurrence
Retrospective Studies

Substances

Calcineurin Inhibitors
Ligands
Receptors, KIR
Mycophenolic Acid
Methotrexate