Analysis of risk factors for the development of GVHD after T cell-depletedallogeneic BMT: Effect of HLA disparity, ABO incompatibility, and method of T-cell depletion

Multivariate analysis was performed to determine the independent factors af fecting the risk of acute GVHD (aGVHD) grades II to IV and extensive chroni c GVHD (cGVHD) and the rate of survival in 481 recipients of T cell-deplete d (TCD) marrow allografts who received transplants at a single center betwe en 1991 and 2000. All patients received grafts partially depleted of CD3(+) T cells by complement-mediated lysis using 2 narrow-specificity monoclonal antibodies (MoAbs), T10B9.1A-31 (n = 400) or Muromonab-Orthoclone OKT3 (n = 81). Factors considered in the analysis included patient/donor sex, age, cytomegalovirus (CMV) status, and ABO blood group along with T-cell dose, d isease and disease status, donor relationship, HLA antigen (Ag) mismatch (b 7M), growth-factor use, anti-thymocyte globulin use, year of transplantatio n, and the MoAb used for TCD. The results showed an association of HLA MM w ith an increased relative risk (RR) of aGVHD for recipients of grafts from related donors that were greater than or equal to2 Ag MM (n = 73, RR = 2.09 , P =.005), matched unrelated (UR) donors (n = 130, RR = 1.98, P = .004), a nd greater than or equal to2 Ag Mr I UR donors (n = 34, RR = 2.68, P = .003 ) compared with the baseline matched-sibling group (n = 121). INTO increase d risk of aGVHD was seen for 0 to 1 Ag MM family donors (n = 24) or 1 Ag MM UR donors (n = 99). aGVHD risk was increased with minor, but not major or major-minor, ABO disparity (RR = 2.0, P =.003) compared with that of ABO-id entical pairs. We found less effective TCD and resultant higher T-cell dose for recipients of grafts that were T cell depleted using OKT3. However, th e use of OKT3 and not the T-cell dose was associated with increased aGVHD r isk (RR of 1.84, P = .001). Increased risk of extensive cGVHD was associate d with patient age of > 20 years (RR = 2.2, P < .0001) and with CMV status (positive patient/negative donor, RR = 1.9, P = .002). Decreased survival w as associated with older age (> 20 years), a greater than or equal to2 Ag M M related donor, a 1 or greater than or equal to2 Ag MM UR donor, risk grou p, and a CMV positive patient/-negative donor pair. There was no difference in survival for 0 to 1 Ag MM related or matched UR donors compared with th e baseline group. These data indicate that there are quantitative as well a s potential qualitative differences in outcome depending on the TCD method. Expected and unexpected risk factors for GVHD and survival were associated with partial TCD. Our data support the consideration of ABO match in donor selection, the preferential selection of CMV positive donors for CMV-posit ive recipients, and the acceptance of 1 but not greater than or equal to2 A g HLA MM donors.