Successful Clearance of Donor Specific Anti-HLA Antibodies after Desensitization with Rituximab, Velcade and Plasma-Exchange Followed By a Haploidentical Stem Cell Transplantion with Post-Transplantation Cyclophosphamide
Authors: Furst Sabine , Maisano Valerio , Basire Agnes , Granata Angela , Legrand Faezeh , Devillier Raynier , Harbi Samia , Castagna Luca , Picard Christophe , Lemarie Claude , Chabannon Christian , Blaise Didier 
Published: November 2020

Background: T cell - replete haploidentical stem cell transplantation (haploSCT) is increasingly performed and has expanded donor pool and transplant option for many patients (pt). However, the presence of recipient antibodies against donor HLA antigens (DSA) have been reported to be associated with engraftment failure and may limit the access to transplantation as the only lifesafing treatment modality. Guidelines for detection and treatment of DSA have been recently published but no standardized desensitization schedule exists so far. We report here the results of our institutional desensitization procedure initially developed for highly immunized patients with severe sickle cell disease undergoing haploSCT and then further adapted to all pt with DSA undergoing a mismatched allogeneic SCT.
Methods: From March 2014 to July 2019, 20 pt had detectable DSA and did perform desensitization before undergoing a haploSCT. The DSA level was determined by using the LUMINEX technique (One Lamda, Inc). In case of positivity, the single antigen test was done to identify each class I and II HLA antibody-specificity. The values were expressed in mean fluorescence intensity (MFI). DSA were considered positive if the MFI value was ≥ 1000. The desensitization treatment included Rituximab 375 mg/m2, Velcade 1.3 mg/m2 and Plasma-Exchange followed by intravenous polyvalent immunoglobulins (Figure). DSA level controls were done routinely during desensitization, before starting the conditioning regimen and the day before graft injection. Pt who did not decrease DSA levels were not considered for haploSCT.
Results: Median age was 61 years (range, 22-73). Diagnosis was acute myeloid leukemia in 6 pt, myelodysplastic / myeloproliferative syndrome in 10 pt, chronic lymphocytic leukemia in 1 pt and severe sickle cell disease in 3 pt. All donors were first-degree family members. Half of the pt were women [donor-recipient sex match: F/F=4; M/F=6; F/M=5; M/M=5pt]. The median MFI value before desensitization was 4700 (range, 1000-16000). Most pt (17) had DSAs against HLA class I antigens. Seventeen pt successfully decreased DSA levels to a median MFI value of 500 (range, 500-1200) and could proceed to haploSCT. They all engrafted and no DSA rebound was observed. One pt relapsed during the desensitization procedure and 2 pt with high DSAs above 10000 did not respond with remaining MFI of 16000 and 9500, respectively, and did not undergo haploSCT. One pt with CMML experienced primary graft failure for relapse and one pt with CLL did not engraft for unknown cause.
Conclusions: The presence of DSA under 10000 should not be a barrier to transplantation. Our report shows that the hereby described desensitization schedule effectively cleared DSA allowing engraftment after haploSCT. Further studies are needed to determine the role of specificity and strength of DSA in order to better predict the likelihood of successful desensitization.

Disclosures
Harbi: Sanofi: Honoraria. Blaise:Jazz Pharmaceuticals: Honoraria.