Alternative donor transplantation for severe aplastic anemia: a comparative study of the SAAWP EBMT

• Published in: Blood 2024-07, Vol.144 (3), p.323-333
• Main Authors: Montoro, Juan, Eikema, Dirk-Jan, Tuffnell, Joe, Potter, Victoria, Kalwak, Krzysztof, Halkes, Constantijn J. M., Kulagin, Alexander, Collin, Matthew, Wynn, Robert F., Robinson, Stephen, Nicholson, Emma, Sengeloev, Henrik, Clay, Jennifer, Halahleh, Khalid, Skorobogatova, Elena, Sanz, Jaime, Passweg, Jakob, Mielke, Stephan, Ryhänen, Samppa, Carpenter, Ben, Gedde-Dahl, Tobias, Tholouli, Eleni, Fanin, Renato, Lewalle, Philippe, Kulasekararaj, Austin, Risitano, Antonio, Peffault de Latour, Régis
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Anemia, Aplastic - mortality; Anemia, Aplastic - therapy; Child; Child, Preschool; Female; Graft vs Host Disease - etiology; Graft vs Host Disease - prevention & control; Hematologi; Hematopoietic Stem Cell Transplantation - methods; Humans; Immunologi inom det medicinska området; Klinisk medicin; Male; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Middle Aged; Tissue Donors; Transplantation, Haploidentical - methods; Unrelated Donors; Young Adult
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood.2024024173

•SCT from MUD offers superior survival outcomes for severe aplastic anemia compared with both MMUD and Haplo SCT.•The decision between an MMUD and Haplo donor in the absence of an available MUD remains uncertain. [Display omitted] Selecting the most suitable alternative donor becomes challenging in severe aplastic anemia (SAA) when a matched sibling donor (MSD) is unavailable. We compared outcomes in patients with SAA undergoing stem cell transplantation (SCT) from matched unrelated donors (MUD) (n = 1106), mismatched unrelated donors (MMUD) (n = 340), and haploidentical donors (Haplo) (n = 206) registered in the European Society for Blood and Marrow Transplantation database (2012-2021). For Haplo SCT, only those receiving posttransplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis were included. Median age was 20 years, and the median time from diagnosis to transplantation 8.7 months. Compared with MUD, MMUD (hazard ratio [HR], 2.93; 95% confidence interval [CI], 1.52-5.6) and Haplo (HR, 5.15; 95% CI, 2.5-10.58) showed significantly higher risks of primary graft failure. MUD had lower rates of acute GVHD compared with MMUD and Haplo (grade 2-4: 13%, 22%, and 19%, respectively; P < .001; grade 3-4: 5%, 9%, and 7%, respectively; P = .028). The 3-year nonrelapse mortality rate was 14% for MUD, 19% for MMUD, and 27% for Haplo (P < .001), whereas overall survival and GVHD and relapse-free survival (GRFS) rates were 81% and 73% for MUD, 74% and 65% for MMUD, and 63% and 54% for Haplo, respectively (P < .001). In addition to donor type, multivariable analysis identified other factors associated with GRFS such as patient age, performance status, and interval between diagnosis and transplantation. For patients with SAA lacking an MSD, our findings support MUDs as the preferable alternative donor option. However, selecting between an MMUD and Haplo donor remains uncertain and requires further exploration. In this month’s CME article, Montoro and colleagues compare outcomes in patients with severe aplastic anemia transplanted from alternative donors from the European Society for Blood and Marrow Transplantation (EBMT) database (2012-2021), including matched unrelated donors (MUD), mismatched unrelated donors (MMUD), and haploidentical donors with posttransplant cyclophosphamide (Haplo). Based on this analysis, MUD is preferred, with lower rates of graft failure, graft-versus-host disease (GVHD), and nonrelapse mortality and better overall surviv