The role of HLA matching in unrelated donor hematopoietic stem cell transplantation for sickle cell disease in Europe

• Published in: Bone marrow transplantation (Basingstoke) 2020-10, Vol.55 (10), p.1946-1954
• Main Authors: Gluckman, Eliane, Fuente, Josu de la, Cappelli, Barbara, Scigliuolo, Graziana M., Volt, Fernanda, Tozatto-Maio, Karina, Rocha, Vanderson, Tommaso, Mina, O’Boyle, Farah, Smiers, Frans, Cunha-Riehm, Claudia Bettoni Da, Calore, Elisabetta, Bonanomi, Sonia, Graphakos, Stelios, Paisiou, Anna, Albert, Michael H., Ruggeri, Annalisa, Zecca, Marco, Lankester, Arjan C., Corbacioglu, Selim
• Format: Article
• Language: English
• Subjects: 13/100; 692/699/1541; 692/700/565/2319; Analysis; Antithymocyte globulin; Bone marrow; Bone marrow transplantation; Busulfan; Cell Biology; Clinical trials; Cyclophosphamide; Fludarabine; Graft rejection; Graft-versus-host reaction; Grafting; Grafts; Hematology; Hematopoietic stem cells; Histocompatibility antigen HLA; Internal Medicine; Matching; Medicine; Medicine & Public Health; Peripheral blood; Public Health; Risk analysis; Risk factors; Sickle cell anemia; Sickle cell disease; Stem cell transplantation; Stem Cells; Survival; Tissue typing; Transplantation; Treosulfan
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/s41409-020-0847-z

We report the results of an analysis of unrelated allogeneic hematopoietic stem cell transplantations (HSCT) in 71 patients with sickle cell disease (SCD) transplanted in EBMT centers between 2005 and 2017. Median age was 9.3 years; graft type was bone marrow in 79% and peripheral blood in 21%. Recipient–donor HLA match at high resolution typing was 10/10 in 31, 9/10 in 20, and 8/10 in 4 patients; the other patients had intermediate resolution typing. The most frequent conditioning regimens were fludarabine–thiotepa–treosulfan (64%) or busulfan–cyclophosphamide (12%). Cumulative incidence of neutrophil engraftment was 92%; platelet engraftment was 90%. Eleven patients (15%) experienced graft failure. Grade II–IV acute graft-vs.-host disease (GvHD) was 23%; 3-year chronic GvHD was 23%. Three-year overall survival (OS) was 88 ± 4%. GRFS was 62 ± 6%. HLA matching was the most significant risk factor for OS: 3-year OS was 96 ± 4% in 10/10 group vs. 75 ± 10% in 9–8/10 ( p  = 0.042); GRFS was 69 ± 9% vs. 50 ± 12% ( p  = 0.114), respectively. In conclusion, unrelated donor HSCT is a valid option for SCD patients who lack an HLA-identical sibling donor, preferably in the context of clinical trials. Using a 10/10 HLA-matched unrelated donor yields better survival indicating that HLA matching is an important donor selection factor in this nonmalignant disease.