The impact of graft composition on clinical outcomes in unmanipulated HLA-mismatched/haploidentical hematopoietic SCT.
This study examines the absolute numbers and relative proportions of CD4+, CD8+, CD14+ and CD34+ cells contained in allografts and their impact on early engraftment and later clinical outcomes in 141 patients with hematological malignancies who underwent unmanipulated HLA-mismatched/haploidentical hematopoietic SCT without in vitro T-cell depletion. These patients received G-CSF-primed BM grafts (G-BM) and peripheral blood grafts (G-PB) following a modified regimen of BU/CY 2 plus antithymocyte globulin. Multivariate analysis showed that high CD34+ cell numbers were associated with accelerated plt engraftment (P=0.001). Meanwhile, patients with a higher CD4/CD8 ratio in G-BM (> or =1.16) had a survival disadvantage (P<0.01) and a trend towards relapse (P=0.086) after controlling for disease status. A higher CD4/CD8 was also associated with a significantly increased risk of acute GVHD grades II-IV (P=0.013), even after adjusting for an ABO major mismatch. No aspect of graft composition affected neutrophil engraftment or chronic GVHD. In conclusion, the differences in CD34+ cell dose and the CD4/CD8 ratio in grafts seem to affect engraftment and clinical outcomes; in particular, a lower CD4/CD8 ratio in primed BM graft is associated with a survival benefit.
Luo
X-H
XH
Peking University Institute of Hematology, Peking University People's Hospital, Beijing, China.
Chang
Y-J
YJ
Xu
L-P
LP
Liu
D-H
DH
Liu
K-Y
KY
Huang
X-J
XJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology*; D002648:Child; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
D015703:Antigens, CD; D006680:HLA Antigens