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.