NKG2D gene polymorphism has a significant impact on transplant outcomes after HLA-fully-matched unrelated bone marrow transplantation for standard risk hematologic malignancies

• Published in: Haematologica (Roma) Vol. 94; no. 10; pp. 1427 - 1434
• Main Authors: Espinoza, J. Luis, Takami, Akiyoshi, Onizuka, Makoto, Sao, Hiroshi, Akiyama, Hideki, Miyamura, Koichi, Okamoto, Shinichiro, Inoue, Masami, Kanda, Yoshinobu, Ohtake, Shigeki, Fukuda, Takahiro, Morishima, Yasuo, Kodera, Yoshihisa, Nakao, Shinji, Japan Marrow Donor Program
• Format: Journal Article
• Language: English
• Published: Pavia Ferrata Storti Foundation 01-10-2009
• Subjects: Adolescent; Adult; Biological and medical sciences; Bone Marrow Transplantation - methods; Bone Marrow Transplantation - mortality; Child; Child, Preschool; Female; Follow-Up Studies; Haplotypes; Hematologic and hematopoietic diseases; Hematologic Neoplasms - genetics; Hematologic Neoplasms - mortality; Hematologic Neoplasms - surgery; Histocompatibility Testing - methods; HLA Antigens - genetics; Humans; Infant; Living Donors; Male; Medical sciences; Middle Aged; NK Cell Lectin-Like Receptor Subfamily K - genetics; Original; Polymorphism, Genetic - genetics; Retrospective Studies; Risk Factors; Treatment Outcome; Young Adult; HLA-System; Prognosis; Genetic variability; Hematology; Unrelated donor; NKG2D receptor; Stem cell; Major histocompatibility system; Hematopoietic cell; Homograft; Genotype; Malignant hemopathy; LNK1; HNK1; Standards; bone marrow transplantation; NKG2D; Risk factor; Bone marrow; Graft; Single nucleotide polymorphism; Histocompatibility; Cancer
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2009.008318

1 Department of Hematology and Oncology, Kanazawa University Hospital, Kanazawa
2 Department of Hematology and Oncology, Tokai University School of Medicine, Isehara
3 Department of Hematology, Meitetsu Hospital, Nagoya
4 Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo
5 Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya
6 Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo
7 Department of Hematology and Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka
8 Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama
9 Hematopoietic Stem Cell Transplantation Unit, National Cancer Center Hospital, Tokyo
10 Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya
11 Department of Promotion for Blood and Marrow Transplantation, Aichi Medical University, Nagoya, Japan
Correspondence: Akiyoshi Takami, M.D., Ph.D., Department of Hematology & Oncology, Kanazawa University Hospital, 13-1 Takaramachi, Kanazawa, 920-8641, Japan. E-mail: takami{at}med3.m.kanazawa-u.ac.jp
Background: NKG2D, an activating and co-stimulatory receptor expressed on natural killer cells and T cells, plays pivotal roles in immunity to microbial infections as well as in cancer immunosurveillance. This study examined the impact of donor and recipient polymorphisms in the NKG2D gene on the clinical outcomes of patients undergoing allogeneic T-cell-replete myeloablative bone marrow transplantation using an HLA-matched unrelated donor.
Design and Methods: The NKG2D polymorphism was retrospectively analyzed in a total 145 recipients with hematologic malignancies and their unrelated donors. The patients underwent transplantation following myeloablative conditioning; the recipients and donors were matched through the Japan Marrow Donor Program.
Results: In patients with standard-risk disease, the donor NKG2D-HNK1 haplotype, a haplotype expected to induce greater natural killer cell activity, was associated with significantly improved overall survival (adjusted hazard ratio, 0.44; 95% confidence interval, 0.23 to 0.85; p =0.01) as well as transplant related mortality (adjusted hazard ratio, 0.42; 95% confidence interval, 0.21 to 0.86; p =0.02), but had no impact on disease relapse or the development of grade II–IV acute graft-versus-host disease or chronic graft-versus-host disease. The NKG2D polymorphism did not significantly influence the transplant outcomes in patients with high-risk disease.
Conclusions: These data suggest an association between the donor HNK1 haplotype and better clinical outcome among recipients, with standard-risk disease, of bone marrow transplants from HLA-matched unrelated donors.
Key words: NKG2D, HNK1, LNK1, unrelated donor, bone marrow transplantation, single nucleotide polymorphism.