Discussion
There is consensus that ABO incompatibility causes immune complications after HSCT (pure red cell regenerative arrest [PRCA] and early or delayed hemolysis). However, conflicting data persist regarding the effect of ABO incompatibility on complications such as post-transplant survival and GVHD incidence and severity [13,14]. Few studies addressed survival after ABO-incompatible allogeneic peripheral blood stem cell transplantation (PBSCT) in AA patients, and this group of children is even less well known. Therefore, we analyzed the clinical outcome of ABO incompatibility after allo-HSCT.
A clinical study [15] reported that AA patients might produce more cytotoxic T cells sensitive to donor major histocompatibility complexes (MHCs) during allogeneic HSCT due to repeated transfusions. This increase in cytotoxic T cells can lead to a higher implantation failure rate and transplantation-related mortality. However, we determined that the 6-year OS rate was higher in patients with bidirectional incompatibility compared to those with the major incompatibility, minor incompatibility, and ABO-compatible groups. However, the four data groups were not significantly different, which was consistent with most current findings [16,17].
The ABO blood group system is considered the most important of the 36 blood group systems. ABO antigens are tissue blood group antigens and can be found in the endothelium, epidermal, mucosal epithelium, and on lymphocytes and platelets. In the present study, we observed no difference in the neutrophil and platelet implantation status among the four groups, which was consistent with previous findings [18,19]. This suggested that ABO blood group incompatibility did not affect leukocyte or platelet recovery.
Previous studies suggested that ABO-incompatible transplantation might increase GVHD risk due to the expression of blood cell antigens on endothelium and epithelial tissues, which the GvH response can target [20]. However, our data revealed a significant difference in the aGVHD incidence among the four groups (p = 0.0462). Surprisingly, the ABO-compatible recipients had the highest incidence of aGVHD, contradicting most previous conclusions [21,22]. Both studies suggested that ABO incompatibility increases the risk of aGVHD, particularly in secondary ABO incompatibility. Our data suggested that cGVHD occurrence was not associated with the presence or absence of ABO compatibility.
ABO incompatibility increases the risk of immune-mediated hematologic events, including hemolytic responses, passenger lymphocyte syndrome (PLS), and PRCA, due to immunological incompatibility between donors and recipients. A hemolytic response can occur in both major and minor ABO-incompatible transplants. However, it can be successfully avoided through antibody removal treatment or grafts with removed red blood cells. PLS is more commonly observed in small ABO-incompatible transplants with limited prevalence and is generally reported in case studies [1]. PRCA is more prevalent in large ABO-incompatible transplants (prevalence: 1–7.5%) [23,24]. None of these complications were observed in our patients during graft infusion. The absence of these complications in our study could be attributed to variations in primary conditions across research sites or individuals.
The univariate analysis demonstrated that aGVHD and TMA significantly affected survival, while ABO compatibility did not exhibit a significant effect. These findings contradicted the results reported by Helming [15] and other studies conducted on youngsters. Although we included a substantial number of affected children, the limited number of AA children (n = 37, 17.1%) might have influenced the inconsistent outcomes. Therefore, it is crucial to conduct multicenter investigations to validate or challenge our findings.
One strength of our study is its focus on a consistent cohort of children with AA, which distinguishes it from most previous studies in the field. Unlike current research that includes a broader range of disorders and examines all HSCT recipients, we specifically examined the effect of ABO compatibility on children with AA. This distinction might explain the differences between our analysis results and some recent outcomes. However, a weakness of our study is that it is a retrospective analysis, which inherently carries the bias of examining retrospective data. Factors that were not studied, such as ABH secretory state, graft mononuclear cell composition, or the presence of donor-specific anti-HLA antibodies, can all influence graft failure and rejection. These factors might moderate the effect of ABO incompatibility on the final clinical outcome of children undergoing allogeneic HSCT. Based on this retrospective assessment, we concluded that ABO incompatibility has minimal effects on HSCT efficiency and is not a significant barrier to donor selection.