Background: The impact of ABO incompatibility between recipient and donor on the outcome of hemato- poietic stem cell transplantation (HSCT), on the immune- hematologic (IH) complications and on the role of IH monitoring before and after HSCT are still debated. The aim of this study was to evaluate the impact of ABO mismatch on the development of immediate and late IH complica- tions, DFS, OS, GVHD and TRM. Moreover, we analyzed the efficacy of the protocol used at the“Sapienza”University of Rome to manage ABO incompatibility in patients undergoing a HSCT. Methods: From January 2013 to December 2016, we prospectively analyzed 104 consecutive patients (64 males/ 40 females) receiving a HSCT:29.8% from a matched related donor, 53.8% from a matched unrelated donors,1.9% from a cord blood,14.4% from a haploidentical donor. Within 30 days prior to the HSCT and every week up to 30 days post-HSCT, then every 15 days until RBC engraftment, patients underwent a complete IH assessment, including ABO and Rh blood phenotype, indirect antiglobulin test, direct antiglobulin test, anti-A and anti-B IgM, and IgG titration in ABO-incompatible cases. Graft manipulation or desensitization strategies were defined according to ABO incompatibility, donor sex (all female donor grafts were plasma depleted), donor's transfusion history. RBC and PLT transfusion support was established according to IH features. Data were prospectively collected in a database, including age, sex, diagnosis, donor hematopoietic stem cell source, conditioning regimen and post-HSCT complications such as CMV/EBV infections, venous-occlusive disease, hemorrhagic cystitis, hemolytic- uremic syndrome and GVHD. Results: Fourty-nine of 104 patients (47%) were ABO- identical and 55 (53%) ABO-incompatible (23 major, 25 minor, 7 bidirectional). Seven patients (6.7%) received a non-myeloablative conditioning regimen, 33(31.7%) a reduced intensity and 64 patients (61.5%) a myeloablative regimen. Stem cell source was bone marrow for 52% of patients, peripheral blood for 46% of patients, cord blood for 2%. In 61 cases (58.7%), a plasma depletion from the graft was carried out, in 2 cases the graft was subjected to erythro-sedimentation, in 2 other cases both plasma and RBC depletion were performed. Two patients were treated with plasmapheresis (1 ABO bidirectional incompatibility and 1 ABO major + high titer anti-K alloantibody). Hemolysis during infusion was observed in 17% of patients with ABO major and bidirectional incompatibility. Donor engraftment in PMN, PLTs and RBCs, graft failure or other complications did not differ between patients with or without ABO incompatibility; only 1 patient with a major ABO incompatibility suffered from a pure red cell aplasia. Two patients experienced autoimmune hemolytic anemia. Factors associated with a prolonged blood support (RBC) were ABO incompatibility (p=0.01), hemorrhagic cystitis (p=0.01) and haploidentical transplant (p=0,004). ABO incompatibility did not show a significant impact on GVHD, OS and DFS. Conclusions: In this prospective study, we confirm that ABO incompatibility does not represent a barrier to allo- HSCT. It is, however, associated with a prolonged transfusional requirement. In our experience, ABO incom- patibility does not influence the risk of GVHD. A strict IH monitoring, as a shared standard procedure, allows to perform an appropriate transfusion support and to treat patients efficiently, limiting post-HSCT IH complications
