Impact of human leucocyte antigen mismatch on graft-versus-host disease and graft failure after reduced intensity conditioning allogeneic haematopoietic stem cell transplantation from related donors.
The impact of human leucocyte antigen (HLA) incompatibility between donor and recipient on graft-versus-host disease (GVHD) and graft failure after reduced-intensity conditioning stem cell transplantation (RICT) remains to be elucidated. We retrospectively analysed outcome in 341 patients who underwent RICT from related donors for haematological malignancies. The overall cumulative incidence of grade II-IV acute GVHD (aGVHD) was 40% for all subjects; 39% in recipients with HLA-matched donors, 44% in those with one-locus-mismatched donors, and 50% in those with two- to three-loci-mismatched donors. In a Cox regression model adjusted for potential confounders, the tendency for grade II-IV aGVHD (P=0.01), chronic GVHD (cGVHD) (P=0.05) and graft failure (P=0.033) increased with HLA disparity. Use of peripheral blood grafts instead of marrow was a risk factor for cGVHD. Use of antithymocyte globulin was associated with reduced aGVHD and cGVHD. Overall survival (OS) in recipients of two- to three-loci-mismatched RICT at 2 years (18%) was significantly worse than that in patients who received one-locus-mismatched RICT (51%) and HLA-matched RICT (48%) (P<0.0001). A two- to three-loci mismatch was identified as an independent risk factor for OS (P<0.001), but there was no significant difference in OS between HLA-matched and one-locus-mismatched RICT. HLA incompatibility between the donor and recipient is an important risk factor for graft failure, aGVHD, cGVHD and OS after RICT. RICT from a one-locus-mismatched donor may represent an effective alternative approach in patients with high-risk malignancies who lack HLA-matched related donors.
Teshima
Takanori
T
Centre for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka, Japan. tteshima@cancer.med.kyushu-u.ac.jp
Matsuo
Keitaro
K
Matsue
Kosei
K
Kawano
Fumio
F
Taniguchi
Shuichi
S
Hara
Masamichi
M
Hatanaka
Kazuo
K
Tanimoto
Mitsune
M
Harada
Mine
M
Nakao
Shinji
S
Abe
Yasunobu
Y
Wake
Atsushi
A
Eto
Tetsuya
T
Takemoto
Yoshinobu
Y
Imamura
Masahiro
M
Takahashi
Satoshi
S
Ishida
Yoji
Y
Kanda
Yoshinobu
Y
Kasai
Masaharu
M
Takaue
Yoichi
Y
D000208:Acute Disease; D002908:Chronic Disease; D006084:Graft Rejection; D006086:Graft vs Host Disease / Q000276:immunology* / Q000401:mortality; D006680:HLA Antigens / Q000276:immunology*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000601:surgery*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods / Q000401:mortality; D006648:Histocompatibility; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D015996:Survival Rate; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
D006680:HLA Antigens; D007166:Immunosuppressive Agents