Purpose
Allogeneic stem cell transplantation (SCT) remains a curative option for patients suffering from hematological disorders. However, long-term survival is mainly influenced by treatment related toxicity, graft versus host disease (GVHD), disease relapse and graft failure. HLA mismatched related, unrelated donors are increasingly used as alternative stem cell sources. In this setting, the presence of donor specific HLA antibodies (DSA) in the recipient has been shown to be associated with higher incidences of graft rejection in both solid organ transplantation and HLA-mismatched SCT. There is currently no guidelines on the management of patients with DSA.
Materials and Methods
We evaluated 46 patients undergoing SCT using only peripheral blood stem cells and we explored the relation between the presence of DSA and the frequency of complications including graft failure, GVHD, relapse and death. We also assessed the impact of using pre-transplant desensitization treatment. All included patients were positive for HLA-antibodies (Class I, Class II or both) measured by Luminex technology before transplant. They all have been treated in our centre between March 2015 and July 2018.
Results
Ten patients developed DSA before or after SCT (21.7%), 8 with a mismatched unrelated donor (two mismatches with both HLA class I and II, and five with class II) and 2 haplo-identical grafts. The only one
patient who developed primary graft failure was DSA positive. We noted 17 deaths (36.9%), 18 GVHD (39%) and 17 relapses (36.9%).The presence of DSA did not affect significantly mortality, GVHD, engraftment or relapse rate. Five out of the DSA positive patients (50%) were treated with a desensitization procedure including rituximab, intravenous gammaglobulins and plasmapheresis. This procedure was also performed in non-DSA patients in a total of 15 patients (32.6%). Despite desensitization, we observed an increase in DSA in two patients. The procedure did not result in a statistically significant incidence of outcome.
Conclusion
DSA are described to be an important cause of graft failure. Despite the absence of significant impact on outcomes, our results support the idea of screening patient for HLA antibodies before SCT, particularly in the
setting of mismatched related or unrelated donors. When DSA are detected, alternative donors and desensitization therapy should be considered. Prospective studies and further therapeutic guidelines are
warranted.

Donor Specific Anti-HLA Antibodies and Allogeneic Hematopoietic Stem Cell Transplantation