Incidence and Role of Recipient-Specific Antibodies in Allogeneic Hematopoietic Cell Transplantation from Mismatched Related Donors

• Published in: Transplantation and cellular therapy 2024-01, Vol.30 (1), p.99.e1-99.e10
• Main Authors: Sadowska-Klasa, Alicja, Dukat-Mazurek, Anna, Zielińska, Hanna, Dębska-Zielkowska, Joanna, Piekarska, Agnieszka, Moszkowska, Grażyna, Mensah-Glanowska, Patrycja, Zaucha, Jan Maciej
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Anti-HLA antibodies; Antilymphocyte Serum; Graft Rejection; Graft vs Host Disease - epidemiology; Graft vs Host Disease - etiology; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic Stem Cell Transplantation - methods; Humans; Incidence; Middle Aged; Mismatched donor; RSA; TA-TMA; Thrombotic Microangiopathies - complications; Transplantation, Homologous - adverse effects; Young Adult
• ISSN: 2666-6367; 2666-6367
• DOI: 10.1016/j.jtct.2023.10.015

•Anti-HLA recipient-specific antibodies (RSAs) are often present in related mismatched donor population.•The presence of RSAs may be associated with higher rates of transplantation-associated thrombotic microangiopathy (TA-TMA) but not with acute graft-versus-host disease.•Antibody-mediated complement activation might be an additional factor influencing endothelial damage and TA-TMA occurrence. High titer of donor-specific antibodies (DSAs) increases the risk of graft rejection after mismatched related hematopoietic cell transplantation (HCT). There are no data regarding the incidence of anti-HLA recipient-specific antibodies (RSAs) and their role after transplantation. Here we aimed to identify the incidence of RSAs in a mismatched related hematopoietic cell donor population and their possible impact on immune-mediated complications, such as acute graft-versus-host disease (aGVHD), and complications resulting from endothelial injury, such as transplantation-associated thrombotic microangiopathy (TA-TMA) and veno-occlusive disease (VOD). We prospectively analyzed the incidence of anti-HLA antibodies in 28 mismatched related pairs of recipients and their donors who underwent HCT at our center between 2020 and 2022. In positive samples screened for anti-HLA class I and/or II antibodies, the specificity of the HLA antibodies was analyzed. All recipients had a hematologic malignancy and received a myeloablative conditioning regimen and immunosuppression consisting of post-transplantation cyclophosphamide, tacrolimus, and mycophenolate mofetil. Patients were tested for TA-TMA and aGVHD development during routine post-transplantation visits up to 100 days post-transplantation. We used modified Jodele criteria for TA-TMA diagnosis, and based aGVHD grading on the MAGIC criteria. VOD was assessed using the European Society for Blood and Marrow Transplantation. Anti-HLA antibodies were detected in 12 donors (43%) and in 9 recipients (32%). There were no significant differences between donors and recipients according to age (median, 42 years [range, 17 to 69 years] versus 39 years [range, 8 to 68 years]), sex, or pregnancy history. No transfusion history was noted in the donor group (P < .05). RSA antibodies were present more often than DSAs and were detected in 9 out of 12 (75%) anti-HLA-positive donors and in only 2 out of 9 (22%) recipients, respectively (P < .05). During the follow-up, 11 patients (39%) developed aGVHD, including grade I-II in 9 (32%) and grade I