ABO incompatibility between donor and recipient is not considered a barrier for successful allogeneic hematopoietic stem cell transplantation (HSCT). However, it is well established that major ABO incompatibility is associated with several immunohematological complications such as delayed hemolysis, delayed erythropoiesis, pure red cell aplasia and prolonged transfusion requirements due to the persistent presence of host-derived antibodies. Nevertheless, conflicting data still exist as to its influence on graft-versus-host disease (GvHD) incidence, relapse rate and survival. To further investigate the relevance of ABO major mismatch on transplant outcome, we retrospectively analyzed results from 414 patients with major or major/minor ABO-mismatched related and unrelated allogeneic transplantation performed between 1978 and 2005. Of the 414 patients, 226 (55%) received bone marrow (BM), 138 (33%) peripheral blood stem cells (PBSC) and 49 (12%) cord blood (CB) transplantation. Transplants were performed for both malignant (71%) and non malignant (29%) hematological diseases using myeloablative (81%) and non myeloablative (19%) conditioning regimens. Transplant outcome was assessed by comparison with results from a 395-patient ABO-compatible population with similar characteristics with respect to period of transplant, stem cell source, conditioning regimen, GvHD prophylaxis and donor type. Median time to red cells transfusion independence was significantly longer in ABO-incompatible marrow recipients (median time 63 days vs. 41 days, p=0.001) with faster disappearance of anti-donor IgM hemagglutinins in unrelated recipients (median time 36 days vs. 44 days, p=0.03) and in patients with grade≥2 aGVHD (median time 35 days vs. 59 days, p=0.001). However, erythroid reconstitution was not significantly delayed in PBSC and CB transplantation, whatever donor type or aGVHD occurrence. A strong correlation between ABO incompatibility and GVHD incidence was found in PBSC recipients with a 2.1-fold increased likelihood (1.8–3.1, 95% CI, p=0.01) of developing grade≥2 aGVHD, all patients receiving cyclosporine A-based prophylaxis regimen. An effect of ABO mismatch was also found on relapse rate and overall survival in that population but without reaching statistical significance (35% vs. 41%, p=0.055 and 39 months vs. 34 months, p=0.055). Among CB transplant recipients, we also found an impact of ABO incompatibility on neutrophil engraftment with borderline statistical significance (median time to reach neutrophil count>1000/μL: 29 days vs. 23 days, p=0.05). No effect was seen on platelet recovery, GvHD incidence or relapse rate in this subgroup. When performing multivariate analysis in Cox regression model for effect on relapse rate in the whole population, donor/recipient ABO mismatch and c.GVHD appeared to be the 2 only factors associated with a lower risk of relapse (RR=0.65, 95% CI, p=0.04 and RR=0.55, 95% CI, p=0.035, respectively). Overall, our results confirm the impact of aGVHD and donor type in red blood cells transfusion requirements in bone marrow ABO-mismatched recipients. They also tend to show beneficial impact of ABO incompatibility on relapse rate, especially in PBSCT. Taken together, these data may influence donor choice, i.e.: select ABO-matched donor for bone marrow and cord blood transplants (to favor hematological recovery) and, may be ABO mismatched donor for peripheral blood transplants with the aim to stimulate alloreactivity in patients with hematological malignancy.

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