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

Abstract

Multivariate analysis was performed to determine the independent factors affecting the risk of acute GVHD (aGVHD) grades II to IV and extensive chronic GVHD (cGVHD) and the rate of survival in 481 recipients of T cell-depleted (TCD) marrow allografts who received transplants at a single center between 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, disease, and disease status, donor relationship, HLA antigen (Ag)mismatch (MM), growth-factor use, anti-thymocyte globulin use, year of transplantation, and the MoAb used for TCD. The results showed an association of HLA with an increased relative risk (RR) of aGVHD for recipients of grafts from relateddonors that were > or =2 Ag MM (n = 73, RR = 2.09, P = .005), matched unrelated (UR) donors (n = 130, RR = 1.98, P = .004), and > or =2 Ag MM UR donors (n = 34, RR = 2.68, P = .003) compared with the baseline matched-sibling group (n = 121). No increased 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-identical pairs. We found less effective TCD and resultant higher T-cell dose for recipients of grafts that were T cell depleted using OKT3. However, the use of OKT3 and not the T-cell dose was associated with increased aGVH-D risk (RR of 1.84, P = .001). Increased risk of extensive cGVHD was associated 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 was associated with older age (>20 years), a > or =2 Ag MM related donor, a 1 or > or =2 Ag MM UR donor, risk group, 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 the baseline group. These data indicate that there are quantitative as well as 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-positive recipients, and the acceptance of 1 but not > or =2 Ag HLA MM donors.

Lack of effect of donor–recipient ABO mismatching on outcome following allogeneic hematopoietic stem cell transplantation

“…[13][14][15][16][17][18][19][20][21]33,34 However, the relative ease of testing for such correlations, the well-known and highly prevalent phenomenon of publication bias, and the presence of a number of studies in the literature that have failed to confirm such correlations [22][23][24][25][26][27][28][29][30][31][32] led us to hypothesize that publication bias itself may be partly or wholly responsible for the appearance of such reports in the literature. To our knowledge, the current study is the only investigation of these issues in the BMT literature in which the authors have specified a single, precisely defined primary statistical end point before initiating the actual analysis, and used formal statistical adjustments to reduce the risk of reporting false-positive associations involving secondary end points.…”

“…In addition, the current study may be more widely applicable than the CIBMTR study because the CIBMTR study included only patients with early-stage leukemia, whereas the current study included an unselected consecutive series of transplants and thus represents all of the commonly transplanted diagnoses. We and others have hypothesized 13,15,16,26 that minor ABO mismatches between BMT donors and recipients might be associated with an increased incidence of GVHD given the importance of the ABO system in the solid organ transplant setting and given the expression of recipientderived ABO antigens on essentially all host nucleated cells, which could potentially serve as a target for incoming donor T-cells. However, neither the current study nor the large recently published CIBMTR study 32 just mentioned supports this hypothesis.…”

“…[1][2][3][4][5][6][7][8][9][10][11][12] However, the literature contains strikingly disparate opinions regarding the potential effect of ABO mismatching on other important outcome parameters including the incidence of death, relapse, graft-versus-host disease (GVHD), and transplant-related-mortality. Specifically, various investigators have concluded that ABO mismatching increases, [13][14][15][16][17][18][19][20][21] does not affect, [22][23][24][25][26][27][28][29][30][31][32] or decreases, [33][34] the incidence of one or more of the latter events.…”

Multidrug-resistant cytomegalovirus infection in a pediatric stem cell transplantation patient

“…Risk factors for CMV infection in HSCT patients include CMV seropositivity of donor and recipient, allogeneic transplantation (especially with T cell-depleted unrelated or HLA-mismatched donors) and cell source. Cord blood recipients have both longer and higher cumulative incidences of CMV infection compared to peripheral blood or allogeneic bone marrow recipients from related or unrelated donor origin (Keever-Taylor et al, 2001;Yoon et al, 2009;Yi and Kim, 2012). In HSCT patients, cellular immunity is mainly significantly impaired during the first 100 days post-transplant.…”

Impact of ABO blood group mismatch in alemtuzumab-based reduced-intensity conditioned haematopoietic SCT

“…2,8,[12][13][14] Immunological effects of ABO BD and MJ mismatch include acute haemolysis, pure red cell aplasia and delayed engraftment, leading to increased transfusion requirements. [15][16][17] In HSCT patients with ABO MN mismatch, acute or delayed haemolysis occur in up to 15-30% due to the development of passenger lymphocyte syndrome.…”