ANTI-HLA DONOR SPECIFIC ANTIBODIES (DSA) IN THE TRANSPLANTATION OF HEMATOPOIETIC STEM CELLS AND DESENSITIZATION STRATEGY. UNICENTRIC PERSPECTIVE STUDY

Background: In the setting of hematopoietic stem cell transplantation (HSCT), the detection of antibodies (Ab) directed against donor specific HLA antigens (DSA) represents a contraindication to proceed with the same donor. In many cases, there is insufficient time to search for alternative donors and it is necessary to plan an immunosuppressive strategy to decrease the DSA levels, thus reducing the risk of graft failure. To date, there is no consensus on desensitization standards to manage DSAs in HSCT. The aim of this study was to evaluate the efficacy of our desensitization strategy. Methods: Anti-HLA Ab research was carried out using the Luminex bead assay (Lifecode Screen and LSA I/II-Immucor). The results were expressed as mean fluorescence intensity (MFI); MFI >1000 was considered positive. In case of a mismatched related donor, a flow cytometric crossmatch test (FCXM) was performed. If the patient had DSAs and only one available donor, the following desensitization strategy was employed: Rituximab on day -15, single-volume plasmapheresis procedures (PP), usually on day -9 and -8, intravenous immunoglobulins on day -7, infusion of HLA selected platelets for DSA absorption in case of persistent antibodies directed against class I HLA antigens. The aim of this schedule was to avoid interferences with chemotherapy and anti-T-cell globulins infused during the condition regimen. Results: Between August 2014 and April 2019, we prospectively screened for DSA 159 consecutive patients candidates to an allogeneic HSCT. Thirty-eight patients (23.9%) showed anti-HLA Ab and 9 of them (5.7%) had DSAs: 6 were treated with the desensitization strategy, applied according to the MFI score and the FCXM result, and they all obtained an engraftment; in 2 cases, an alternative donor was selected and in 1 case the research for an alternative donor is still underway. DSA detection was performed every 7 days after HSCT for the first month and 60, 180 and 365 days following HSCT. Neither a DSA rebound nor other complications were observed during the follow-up. Conclusions: Our prospective analysis underlines the necessity to routinely evaluate the presence of DSAs before an allogeneic mismatched HSCT. Our desensitization schedule, based on the combination of PP, rituximab, IVIG and platelet absorption, proved successful in reducing DSAs. Transplant and transfusion specialists should join to define a consensus for a standard desensitization strategy