Desensitization Therapy Using Sirolimus and Anti-CD20 Monoclonal Antibody Based Regimen In Haploidentical Transplant...

This retrospective study evaluated the efficacy of desensitization therapy using sirolimus and an anti-CD20 monoclonal antibody (n = 47) plus either plasmapheresis (n = 3) or bortezomib (n = 3) in 53 candidates for haploidentical stem cell transplantation (Haplo-SCT) who had pre-transplant donor-specific anti-HLA antibodies (DSA; mean fluorescence intensity [MFI] ≥ 2000). The patients, with a median age of 46 yr (range, 20 to 70), received desensitization therapy within 40 d before transplantation. The median DSA MFI decreased from 9242 (range, 2156 to 20,150) before treatment to 3974 (range, 0 to 16,336) after treatment, 43.4% of the patients became DSA-negative (MFI ≤ 2000), and 62.3% of patients achieved a response, defined as a ≥50% reduction in DSA MFI. Among 31 out of 53 patients who underwent transplantation after receiving myeloablative (n = 19) or reduced-intensity conditioning (n = 12) with infusion of haploidentical allografts and umbilical cord blood, all achieved engraftment without primary graft failure or poor graft function. The 100-d cumulative incidence of acute graft-versus-host disease (GVHD) was 25.8% (95% confidence interval [CI], 10.3% to 41.3%). With a median follow-up of 27 months (range, 3-44), the 1-yr cumulative incidence of chronic GVHD was 31.0% (95% CI, 14.1% to 47.9%). The 1-yr cumulative incidences of relapse and non-relapse mortality were 3.2% (95% CI, 0% to 9.6%) and 10.4% (95% CI, 6.5% to 14.3%), respectively. The 1-yr probabilities of disease-free survival and overall survival were 86.4% and 89.7% (95% CI, 78.5% to 100%), respectively. These findings suggest that sirolimus combined with an anti-CD20 monoclonal antibody based regimen is an effective desensitization strategy that may improve outcomes in DSA-positive Haplo-SCT recipients.