Impact Of ABO Blood Group Incompatibility On The Efficacy Of Treatment Using Single-unit Unrelated Umbilical Cord Blood Transplantation

Objective ABO blood group incompatibility is not thought to affect the success of allogeneic hematopoietic stem cell transplantation(allo-HSCT),and donor-recipient ABO blood group incompatibility occurs in approximately 1/3 of the cases of allo-HSCT.But controversy still exists regarding the impact of donor-recipient ABO blood group incompatibility on hematopoietic reconstitution, the occurrence of graft versus host disease (GVHD), and the long-term survival of patients after allo-HSCT.What’s more,reports of ABO blood group incompatibility in umbilical cord blood transplantation are relatively rare.Therefore,the aim of this study was to investigate the impact of ABO blood group incompatibility on the efficacy of the treatment of patients with hematological malignancies using myeloablative single-unit unrelated donor umbilical cord blood transplantation (UCBT). The time and cumulative incidence of neutrophil, platelet, and red blood cell engraftment; cumulative incidence of acute and chronic graft-versus-host disease; overall survival (OS); the disease-free survival(DFS) rate; and non-relapse mortality (NRM) rate were used as observation indexes for therapeutic efficacy.Methods We retrospectively analyzed 211 cases of patients with malignant hematologic diseases who accepted myeloablative single-unit unrelated donor UCBT at our center between May 2008 and November 2014, including 101 cases of identical ABO blood group,59 cases of minor incompatible ABO blood group,39 cases of major incompatible ABO blood group, and 12 cases of bidirectional incompatible ABO blood group. All the patients received intensified myeloablative conditioning, and a combination of cyclosporine A(CsA) and short-course mycophenolate mofetil (MMF) was given for GVHD prophylaxis. The cohort of patients were followed-up until November 30,2015.Comparisons of continuous variables were performed using a Kruskal-Wallis test. Comparisons of group variables were performed using a chi square test. Estimations of the survival rate were performed using the Kaplan-Meier method. Comparisons of the inter-group survival rates were performed using a log-rank test. The cumulative incidence of neutrophil, platelet, and red blood cell engraftment and the incidence of acute GVHD, chronic GVHD, and NRM are represented using the cumulative incidence rate with competing risks. Multivariate analysis was performed with the Cox proportional hazards regression model. The variables included in the multivariate analysis consisted of age, degree of disease risk (standard risk vs. high risk), conditioning regimen (TBI-based vs. BU-based), HLA compatibility (6/6 vs.5/6 vs.4/6), total nucleated cell (TNC) number in umbilical cord blood, and the number of CD34+ cells.The statistical analysis was performed with SPSS 17.0 software(SPSS Inc.,Chicago, IL, USA). The cumulative incidence rate was calculated using R 3.0 software.(R Foundation for Statistical Computing, Vienna, Austria).A value of P<0.05 indicates statistical significance.Results A comparison of ABO compatible and incompatible UCBT demonstrated no significant differences (P>0.05) in the cumulative incidence of neutrophil, platelet, and red blood cell engraftment; cumulative incidence of grade II to IV acute GVHD; cumulative incidence of grade III to IV acute GVHD; and chronic GVHD, as well as in the OS, DFS, and NRM of patients. None of the patients developed pure red-cell aplasia (PRCA) after UCBT. In the multivariate analysis,CD34+ cell number in umbilical cord blood was positively correlated with neutrophil engraftment (hazard ratio (HR), 1.20;95%CI 1.06-1.37; P<0.01), platelet engraftment (HR,1.26; 95%CI 1.10-1.44; P<0.01), and red blood cell engraftment (HR,1.22; 95%CI 1.08-1.38; P<0.01).What’s more,a difference in HLA compatibility was an independent risk factor for the cumulative incidence of acute GVHD (HR,1.81; 95%CI 1.16-2.81; P<0.01).Conclusion The results showed that ABO blood group incompatibility had no significant impact on the stem cell engraftment,the occurrence of GVHD,and long term survival of malignant hematological disease patients with myeloablative single-unit UCBT;Patients receive ABO-incompatible UCBT may not develop PRCA;ABO blood group incompatibility might not be considered as a major factor in the selection of umbilical cord blood.A lower cord blood CD34+ cell count was associated with a lower incidence of stem cell engraftment.And the HLA typing mismatching between donor and recipient had a impact on the cumulative incidence of grade II to IV acute GVHD.