Donor-specific anti-HLA antibodies (DSAs) in patients undergoing allogeneic hematopoietic stem cell transplantation from mismatched donors on behalf of GITMO and AIBT.

Background: Antibodies directed against donor-specific HLA allele(s)/antigen(s) (DSAs) represent a known risk factor for hematopoietic stem cell transplantation (HSCT) engraftment. Still, the overall management needs to be standardized.
Material and Methods: GITMO and AIBT ran a survey on DSAs in Italian Transplant Programs including mismatched HSCT performed between January 2014 and June 2017.
Results: One-thousand-thirty-three patients were proposed for the study, 804 were evaluable. Overall, 355 (44%) were screened: 91/355 (25.6%) showed anti-HLA antibodies, 23 DSAs (6.5%). Female gender and at least 4 previous pregnancies showed an impact on alloimmunization. Eleven patients with DSAs underwent desensitization. In seven cases no desensitization was employed. An alternative donor was selected for five patients. Neutrophil and platelet engraftment were obtained in 93.6% and 86.6% of the whole population, respectively, and were statistically associated with the absence of anti-HLA antibodies, ABO match, a higher number of infused nucleated cells and lack of a-GvHD. In addition, significant factors for platelet engraftment were the use of leuco-depleted transfusions, HLA match, younger age of the patient. Graft failure (GF) was associated with bone marrow stem cell source, and a lower number of infused CD34+. The detection of antibodies directed against both HLA classes, donor and patient age, the hematologic and molecular remission at HSCT, HLA match, ANC and PLTS engraftment, full donor engraftment within 28 days after HSCT, early and late GF, grade>II a-GVHD showed an impact on OS.
Discussion: Anti-HLA antibodies and DSAs were confirmed as risk factors affecting OS. DSAs were managed with various approaches resulting in stable engraftment in 81.9% of patients. Our study supports the clinical relevance of DSAs detection and management in mmHSCT. A standardized approach of DS is warranted.