TY - JOUR
T1 - The recipient CCR5 variation predicts survival outcomes after bone marrow transplantation
AU - Horio, Tomohiro
AU - Mizuno, Shohei
AU - Uchino, Kaori
AU - Mizutani, Motonori
AU - Hanamura, Ichiro
AU - Espinoza, J. Luis
AU - Onizuka, Makoto
AU - Kashiwase, Koichi
AU - Morishima, Yasuo
AU - Fukuda, Takahiro
AU - Kodera, Yoshihisa
AU - Doki, Noriko
AU - Miyamura, Koichi
AU - Mori, Takehiko
AU - Takami, Akiyoshi
N1 - Funding Information:
This study was supported by grants from the Ministry of Education, Culture, Sports and Technology of Japan (15K09513), the Ministry of Health, Labour and Welfare of Japan (15eK0510002h0002, 15ek0109134h0001, and 16mk0101065h0001), and Bristol-Myers Squibb Foundation Grant (21544355). The funders played no role in the study design, data collection and analysis, the decision to publish, or the preparation of the manuscript.
Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/6
Y1 - 2017/6
N2 - The chemokine receptor CCR5 plays roles in the trafficking of effector cells towards the site of inflammation. We retrospectively examined the impact of the CCR5 variation (rs1800023, -2086A > G) on transplant outcomes in a cohort of 329 patients who underwent unrelated HLA-matched bone marrow transplantation (BMT) for hematologic malignancies through the Japan Marrow Donor Program. A multivariate analysis showed that the recipient CCR5 -2086A/A genotype was significantly associated with a lower relapse rate but not with the development of graft-versus-host disease (GVHD) or transplant-related mortality, thereby resulting in better disease-free and overall survival rates than other variations. The donor CCR5 -2086A/A genotype was associated with a lower incidence of grades 3–4 acute GVHD, which did not improve the survival outcomes. These findings suggest that the recipient CCR5 -2086A/A genotype affects the induction of the graft-versus-tumor effect without augmenting the development of GVHD. CCR5 genotyping in transplant recipients may therefore be a useful tool for evaluating pretransplantation risks.
AB - The chemokine receptor CCR5 plays roles in the trafficking of effector cells towards the site of inflammation. We retrospectively examined the impact of the CCR5 variation (rs1800023, -2086A > G) on transplant outcomes in a cohort of 329 patients who underwent unrelated HLA-matched bone marrow transplantation (BMT) for hematologic malignancies through the Japan Marrow Donor Program. A multivariate analysis showed that the recipient CCR5 -2086A/A genotype was significantly associated with a lower relapse rate but not with the development of graft-versus-host disease (GVHD) or transplant-related mortality, thereby resulting in better disease-free and overall survival rates than other variations. The donor CCR5 -2086A/A genotype was associated with a lower incidence of grades 3–4 acute GVHD, which did not improve the survival outcomes. These findings suggest that the recipient CCR5 -2086A/A genotype affects the induction of the graft-versus-tumor effect without augmenting the development of GVHD. CCR5 genotyping in transplant recipients may therefore be a useful tool for evaluating pretransplantation risks.
KW - Bone marrow transplantation
KW - CCR5
KW - Graft-versus-host disease
KW - Single nucleotide variation
KW - Unrelated donor
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U2 - 10.1016/j.trim.2017.05.003
DO - 10.1016/j.trim.2017.05.003
M3 - Article
C2 - 28487238
AN - SCOPUS:85019076279
VL - 42
SP - 34
EP - 39
JO - Transplant Immunology
JF - Transplant Immunology
SN - 0966-3274
ER -