TY - JOUR
T1 - HLA-DPB1 mismatch induces a graft-versus-leukemia effect without severe acute GVHD after single-unit umbilical cord blood transplantation
AU - Yabe, T.
AU - Azuma, F.
AU - Kashiwase, K.
AU - Matsumoto, K.
AU - Orihara, T.
AU - Yabe, H.
AU - Kato, S.
AU - Kato, K.
AU - Kai, S.
AU - Mori, T.
AU - Morishima, S.
AU - Satake, M.
AU - Takanashi, M.
AU - Nakajima, K.
AU - Morishima, Y.
N1 - Funding Information:
We thank the patients and donors taking part in the umbilical cord blood transplantation, and the staff members of the cord blood collection facilities, transplantation centers, cord blood banks and the Japanese Cord Blood Bank Network for their generous cooperation. We also thank Naoya Takeda for proofreading the manuscript; Aiko Ono, Yuko Yamagiwa and Naoya Takeda for the HLA typing; Manabu Kondo for advice on the statistical analysis; and Kazuyo Ohmura, Miyuki Itoh, Mutsuko Minemoto, Atsuko Ogawa, the late Yoshiharu Suzuki, Tadashi Nagai and Mutsuhiko Minami for their encouragement and support for the research. This work was supported in part by grants from the Japanese Ministry of Health, Labor and Welfare (H23-Immunology-010 and H26-Immunology-106) and by the Practical Research Project for Allergic Diseases and Immunology (Research on Technology of Medical Transplantation) from the Japan Agency for Medical Research and Development (15ek0510002h0302 and 16ek0510002h0003).
Publisher Copyright:
© 2018 Macmillan Publishers Limited.
PY - 2018/1
Y1 - 2018/1
N2 - Although it is known that human leukocyte antigen (HLA)-DPB1 disparity has a strong impact on outcomes in unrelated hematopoietic transplantation with induction of acute graft-versus-host disease (GVHD) and a graft-versus-leukemia (GVL) effect, its role in unrelated umbilical cord blood transplantation (UR-CBT) has yet to be fully clarified. Our current study is being conducted to elucidate the impact of HLA-DPB1 mismatch, along with the effect of other HLA loci mismatches at the allele level. HLA six loci alleles were retrospectively typed in 1157 Japanese donors and patients with leukemia or myelodysplastic syndrome who underwent transplantation with a single unit of cord blood. HLA-DPB1 mismatch was associated with a significant reduction in leukemia relapse (hazard ratio 0.61, Po0.001), whereas the other HLA loci allele-level mismatches did not. No significant effect of HLA-DPB1 mismatch was observed in the risk of acute GVHD, engraftment or mortality. This HLA-DPB1 GVL effect without induction of severe acute GVHD or deterioration of survival rate has not been reported in unrelated bone marrow or peripheral blood stem cell transplantations, suggesting apparent advantages of UR-CBT. Accordingly, selection of an HLA-DPB1 mismatch cord blood might be the preferable choice for single-unit UR-CBT.
AB - Although it is known that human leukocyte antigen (HLA)-DPB1 disparity has a strong impact on outcomes in unrelated hematopoietic transplantation with induction of acute graft-versus-host disease (GVHD) and a graft-versus-leukemia (GVL) effect, its role in unrelated umbilical cord blood transplantation (UR-CBT) has yet to be fully clarified. Our current study is being conducted to elucidate the impact of HLA-DPB1 mismatch, along with the effect of other HLA loci mismatches at the allele level. HLA six loci alleles were retrospectively typed in 1157 Japanese donors and patients with leukemia or myelodysplastic syndrome who underwent transplantation with a single unit of cord blood. HLA-DPB1 mismatch was associated with a significant reduction in leukemia relapse (hazard ratio 0.61, Po0.001), whereas the other HLA loci allele-level mismatches did not. No significant effect of HLA-DPB1 mismatch was observed in the risk of acute GVHD, engraftment or mortality. This HLA-DPB1 GVL effect without induction of severe acute GVHD or deterioration of survival rate has not been reported in unrelated bone marrow or peripheral blood stem cell transplantations, suggesting apparent advantages of UR-CBT. Accordingly, selection of an HLA-DPB1 mismatch cord blood might be the preferable choice for single-unit UR-CBT.
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U2 - 10.1038/leu.2017.202
DO - 10.1038/leu.2017.202
M3 - Article
C2 - 28652579
AN - SCOPUS:85046578463
SN - 0887-6924
VL - 32
SP - 168
EP - 175
JO - Leukemia
JF - Leukemia
IS - 1
ER -
