The recipient CCR5 variation predicts survival outcomes after bone marrow transplantation

Tomohiro Horio; Shohei Mizuno; Kaori Uchino; Motonori Mizutani; Ichiro Hanamura; J. Luis Espinoza; Makoto Onizuka; Koichi Kashiwase; Yasuo Morishima; Takahiro Fukuda; Yoshihisa Kodera; Noriko Doki; Koichi Miyamura; Takehiko Mori; Akiyoshi Takami

doi:10.1016/j.trim.2017.05.003

The recipient CCR5 variation predicts survival outcomes after bone marrow transplantation

Tomohiro Horio, Shohei Mizuno, Kaori Uchino, Motonori Mizutani, Ichiro Hanamura, J. Luis Espinoza, Makoto Onizuka, Koichi Kashiwase, Yasuo Morishima, Takahiro Fukuda, Yoshihisa Kodera, Noriko Doki, Koichi Miyamura, Takehiko Mori, Akiyoshi Takami

Department of Internal Medicine (Hematology)

Research output: Contribution to journal › Article

2 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Transplant Immunology
DOIs	https://doi.org/10.1016/j.trim.2017.05.003
Publication status	Accepted/In press - 2017 Mar 22

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Keywords

Bone marrow transplantation
CCR5
Graft-versus-host disease
Single nucleotide variation
Unrelated donor

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Transplantation

Cite this

Horio, T., Mizuno, S., Uchino, K., Mizutani, M., Hanamura, I., Espinoza, J. L., Onizuka, M., Kashiwase, K., Morishima, Y., Fukuda, T., Kodera, Y., Doki, N., Miyamura, K., Mori, T., & Takami, A. (Accepted/In press). The recipient CCR5 variation predicts survival outcomes after bone marrow transplantation. Transplant Immunology. https://doi.org/10.1016/j.trim.2017.05.003

The recipient CCR5 variation predicts survival outcomes after bone marrow transplantation. / Horio, Tomohiro; Mizuno, Shohei; Uchino, Kaori; Mizutani, Motonori; Hanamura, Ichiro; Espinoza, J. Luis; Onizuka, Makoto; Kashiwase, Koichi; Morishima, Yasuo; Fukuda, Takahiro; Kodera, Yoshihisa; Doki, Noriko; Miyamura, Koichi; Mori, Takehiko; Takami, Akiyoshi.

In: Transplant Immunology, 22.03.2017.

Research output: Contribution to journal › Article

Horio, Tomohiro ; Mizuno, Shohei ; Uchino, Kaori ; Mizutani, Motonori ; Hanamura, Ichiro ; Espinoza, J. Luis ; Onizuka, Makoto ; Kashiwase, Koichi ; Morishima, Yasuo ; Fukuda, Takahiro ; Kodera, Yoshihisa ; Doki, Noriko ; Miyamura, Koichi ; Mori, Takehiko ; Takami, Akiyoshi. / The recipient CCR5 variation predicts survival outcomes after bone marrow transplantation. In: Transplant Immunology. 2017.

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abstract = "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.",

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AU - Mizuno, Shohei

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AU - Espinoza, J. Luis

AU - Onizuka, Makoto

AU - Kashiwase, Koichi

AU - Morishima, Yasuo

AU - Fukuda, Takahiro

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AU - Mori, Takehiko

AU - Takami, Akiyoshi

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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

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KW - Single nucleotide variation

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Access to Document

10.1016/j.trim.2017.05.003