Desensitization therapy for elevated donor-specific antibody levels in haploidentical transplantation in Chilean patients

Allogeneic stem cell transplantation (ALOSCT) is curative for several hematological diseases. Unrelated donors and cord blood stem cells are valid options but haploidentical donors (HAPLO) have been considered the main source of stem cells in several countries, partly due to easy access and low cost of the transplantation process. Unfortunately, some patients have antibodies against the HLA epitopes from family haploidentical donors (donor-specific antibodies [DSA]) which are associated with engraftment failure and lethality. A few strategies exist to reduce or eliminate HLA antibodies that bind to these receptors. In this study, we present our experience with DSA desensitization by retrospectively examining a cohort from our hospital program. Between 2012 and 2023, we performed 243 ALOSCTs, of which 142 were from HAPLO and 56 were from unrelated donors. Nine patients (7%) had elevated DSA levels, most of which were female patients and mostly HAPLO. The median fluorescence intensity for these patients was 22,490 (19,000-28,560). Most of these high DSA patients (80%) received a desensitization procedure that involves plasmapheresis, rituximab, and immunoglobulin. The remaining 20% had severe infections during transplantation, and received rituximab monotherapy instead. The median dose of stem cells infused was 6.5 x 10^6 CD34/kg. Graft-versus-host disease (GVHD) preventative measures for all patients involved post-transplantation cyclophosphamide. Primary graft failure was observed in 45% of DSA elevated patients. For the remaining patients, median granulocyte and platelet engraftment were 14 d (12-16) and 16 d (13-18), respectively. Mortality in patients who did not receive engraftment was 100%. The incidence of mild, chronic GVHD was 15%. In conclusion, the desensitization of DSA in patients provided a 55% rate of engraftment and survival. However, a 45% rate of primary graft failure continued to pose a challenge in patients with DSA and required the development of improved strategies to reduce elevated transplant-related mortality.