Effect of matching of class I HLA alleles on clinical outcome after transplantation of hematopoietic stem cells from an unrelated donor

Takehiko Sasazuki, Takeo Juji, Yasuo Morishima, Naoko Kinukawa, Hidehiko Kashiwabara, Hidetoshi Inoko, Takato Yoshida, Akinori Kimura, Tatsuya Akaza, Nobuhiro Kamikawaji, Yoshihisa Kodera, Fumimaro Takaku, Yoshiaki Nose, Takashi Ono, Takeo Sakamaki, Shunichi Kato, Yuichi Akiyama, Shinichiro Okamoto, Hiroo Dohy, Mine Harada & 1 others Shigetaka Asano

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Abstract

Background. The requirements with respect to HLA compatibility and the relative importance of matching for individual class I and class II HLA alleles in the transplantation of hematopoietic stem cells from unrelated donors have not yet been established. Methods. We performed retrospective DNA typing of alleles at 11 polymorphic loci of HLA genes in 440 recipients of hematopoietic stem cells from unrelated donors who were serologically identical with their respective recipients for HLA-A, B, and DR antigens. Of these recipients, 80 percent had leukemia; the rest had lymphoma, marrow failure, or a congenital disorder. Results. Multivariate analysis showed that incompatibility for HLA-A alleles and incompatibility for HLA-C alleles were independent risk factors for severe acute graft-versus-host disease (GVHD) (HLA-A, P=0.006; HLA-C, P=0.001). Mismatching of HLA-A, but not of HLA-C, alleles was an independent risk factor for death (P<0.001). Mismatching of HLA-C alleles was a significant risk factor for relapse of leukemia (P=0.035). HLA-B disparity was a significant risk factor for both GVHD and death in the univariate analysis, but not in the multivariate analysis. Disparities in class II HLA alleles of the DRB1, DQA1, DQB1, DPA1, and DPB1 loci were not identified as significant risk factors for acute GVHD or death in the multivariate analysis. Conclusions. Genomic typing of class I HLA alleles adds substantially to the success of transplantation of hematopoietic stem cells from unrelated donors, even if the donors are serologically identical to their recipients with respect to HLA-A, B, and DR antigens.

Original languageEnglish
Pages (from-to)1177-1185
Number of pages9
JournalNew England Journal of Medicine
Volume339
Issue number17
DOIs
Publication statusPublished - 1998 Oct 22

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Unrelated Donors
Hematopoietic Stem Cell Transplantation
Alleles
HLA-A Antigens
HLA-C Antigens
HLA-B Antigens
Graft vs Host Disease
Multivariate Analysis
HLA-DR Antigens
Leukemia
HLA-DRB1 Chains
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
DNA Fingerprinting
Hematopoietic Stem Cells
Lymphoma
Bone Marrow
Tissue Donors
Recurrence

ASJC Scopus subject areas

  • Medicine(all)

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Effect of matching of class I HLA alleles on clinical outcome after transplantation of hematopoietic stem cells from an unrelated donor. / Sasazuki, Takehiko; Juji, Takeo; Morishima, Yasuo; Kinukawa, Naoko; Kashiwabara, Hidehiko; Inoko, Hidetoshi; Yoshida, Takato; Kimura, Akinori; Akaza, Tatsuya; Kamikawaji, Nobuhiro; Kodera, Yoshihisa; Takaku, Fumimaro; Nose, Yoshiaki; Ono, Takashi; Sakamaki, Takeo; Kato, Shunichi; Akiyama, Yuichi; Okamoto, Shinichiro; Dohy, Hiroo; Harada, Mine; Asano, Shigetaka.

In: New England Journal of Medicine, Vol. 339, No. 17, 22.10.1998, p. 1177-1185.

Research output: Contribution to journalArticle

Sasazuki, T, Juji, T, Morishima, Y, Kinukawa, N, Kashiwabara, H, Inoko, H, Yoshida, T, Kimura, A, Akaza, T, Kamikawaji, N, Kodera, Y, Takaku, F, Nose, Y, Ono, T, Sakamaki, T, Kato, S, Akiyama, Y, Okamoto, S, Dohy, H, Harada, M & Asano, S 1998, 'Effect of matching of class I HLA alleles on clinical outcome after transplantation of hematopoietic stem cells from an unrelated donor', New England Journal of Medicine, vol. 339, no. 17, pp. 1177-1185. https://doi.org/10.1056/NEJM199810223391701
Sasazuki, Takehiko ; Juji, Takeo ; Morishima, Yasuo ; Kinukawa, Naoko ; Kashiwabara, Hidehiko ; Inoko, Hidetoshi ; Yoshida, Takato ; Kimura, Akinori ; Akaza, Tatsuya ; Kamikawaji, Nobuhiro ; Kodera, Yoshihisa ; Takaku, Fumimaro ; Nose, Yoshiaki ; Ono, Takashi ; Sakamaki, Takeo ; Kato, Shunichi ; Akiyama, Yuichi ; Okamoto, Shinichiro ; Dohy, Hiroo ; Harada, Mine ; Asano, Shigetaka. / Effect of matching of class I HLA alleles on clinical outcome after transplantation of hematopoietic stem cells from an unrelated donor. In: New England Journal of Medicine. 1998 ; Vol. 339, No. 17. pp. 1177-1185.
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abstract = "Background. The requirements with respect to HLA compatibility and the relative importance of matching for individual class I and class II HLA alleles in the transplantation of hematopoietic stem cells from unrelated donors have not yet been established. Methods. We performed retrospective DNA typing of alleles at 11 polymorphic loci of HLA genes in 440 recipients of hematopoietic stem cells from unrelated donors who were serologically identical with their respective recipients for HLA-A, B, and DR antigens. Of these recipients, 80 percent had leukemia; the rest had lymphoma, marrow failure, or a congenital disorder. Results. Multivariate analysis showed that incompatibility for HLA-A alleles and incompatibility for HLA-C alleles were independent risk factors for severe acute graft-versus-host disease (GVHD) (HLA-A, P=0.006; HLA-C, P=0.001). Mismatching of HLA-A, but not of HLA-C, alleles was an independent risk factor for death (P<0.001). Mismatching of HLA-C alleles was a significant risk factor for relapse of leukemia (P=0.035). HLA-B disparity was a significant risk factor for both GVHD and death in the univariate analysis, but not in the multivariate analysis. Disparities in class II HLA alleles of the DRB1, DQA1, DQB1, DPA1, and DPB1 loci were not identified as significant risk factors for acute GVHD or death in the multivariate analysis. Conclusions. Genomic typing of class I HLA alleles adds substantially to the success of transplantation of hematopoietic stem cells from unrelated donors, even if the donors are serologically identical to their recipients with respect to HLA-A, B, and DR antigens.",
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T1 - Effect of matching of class I HLA alleles on clinical outcome after transplantation of hematopoietic stem cells from an unrelated donor

AU - Sasazuki, Takehiko

AU - Juji, Takeo

AU - Morishima, Yasuo

AU - Kinukawa, Naoko

AU - Kashiwabara, Hidehiko

AU - Inoko, Hidetoshi

AU - Yoshida, Takato

AU - Kimura, Akinori

AU - Akaza, Tatsuya

AU - Kamikawaji, Nobuhiro

AU - Kodera, Yoshihisa

AU - Takaku, Fumimaro

AU - Nose, Yoshiaki

AU - Ono, Takashi

AU - Sakamaki, Takeo

AU - Kato, Shunichi

AU - Akiyama, Yuichi

AU - Okamoto, Shinichiro

AU - Dohy, Hiroo

AU - Harada, Mine

AU - Asano, Shigetaka

PY - 1998/10/22

Y1 - 1998/10/22

N2 - Background. The requirements with respect to HLA compatibility and the relative importance of matching for individual class I and class II HLA alleles in the transplantation of hematopoietic stem cells from unrelated donors have not yet been established. Methods. We performed retrospective DNA typing of alleles at 11 polymorphic loci of HLA genes in 440 recipients of hematopoietic stem cells from unrelated donors who were serologically identical with their respective recipients for HLA-A, B, and DR antigens. Of these recipients, 80 percent had leukemia; the rest had lymphoma, marrow failure, or a congenital disorder. Results. Multivariate analysis showed that incompatibility for HLA-A alleles and incompatibility for HLA-C alleles were independent risk factors for severe acute graft-versus-host disease (GVHD) (HLA-A, P=0.006; HLA-C, P=0.001). Mismatching of HLA-A, but not of HLA-C, alleles was an independent risk factor for death (P<0.001). Mismatching of HLA-C alleles was a significant risk factor for relapse of leukemia (P=0.035). HLA-B disparity was a significant risk factor for both GVHD and death in the univariate analysis, but not in the multivariate analysis. Disparities in class II HLA alleles of the DRB1, DQA1, DQB1, DPA1, and DPB1 loci were not identified as significant risk factors for acute GVHD or death in the multivariate analysis. Conclusions. Genomic typing of class I HLA alleles adds substantially to the success of transplantation of hematopoietic stem cells from unrelated donors, even if the donors are serologically identical to their recipients with respect to HLA-A, B, and DR antigens.

AB - Background. The requirements with respect to HLA compatibility and the relative importance of matching for individual class I and class II HLA alleles in the transplantation of hematopoietic stem cells from unrelated donors have not yet been established. Methods. We performed retrospective DNA typing of alleles at 11 polymorphic loci of HLA genes in 440 recipients of hematopoietic stem cells from unrelated donors who were serologically identical with their respective recipients for HLA-A, B, and DR antigens. Of these recipients, 80 percent had leukemia; the rest had lymphoma, marrow failure, or a congenital disorder. Results. Multivariate analysis showed that incompatibility for HLA-A alleles and incompatibility for HLA-C alleles were independent risk factors for severe acute graft-versus-host disease (GVHD) (HLA-A, P=0.006; HLA-C, P=0.001). Mismatching of HLA-A, but not of HLA-C, alleles was an independent risk factor for death (P<0.001). Mismatching of HLA-C alleles was a significant risk factor for relapse of leukemia (P=0.035). HLA-B disparity was a significant risk factor for both GVHD and death in the univariate analysis, but not in the multivariate analysis. Disparities in class II HLA alleles of the DRB1, DQA1, DQB1, DPA1, and DPB1 loci were not identified as significant risk factors for acute GVHD or death in the multivariate analysis. Conclusions. Genomic typing of class I HLA alleles adds substantially to the success of transplantation of hematopoietic stem cells from unrelated donors, even if the donors are serologically identical to their recipients with respect to HLA-A, B, and DR antigens.

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