1. Outcomes of HLA-mismatched HSCT with TCRαβ/CD19 depletion or post-HSCT cyclophosphamide for inborn errors of immunity.
- Author
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Lum SH, Albert MH, Gilbert P, Sirait T, Algeri M, Muratori R, Fournier B, Laberko A, Karakukcu M, Unal E, Ayas M, Yadav SP, Fisgin T, Elfeky R, Fernandes J, Faraci M, Cole T, Schulz A, Meisel R, Zecca M, Ifversen M, Biffi A, Diana JS, Vallée T, Giardino S, Ersoy GZ, Moshous D, Gennery AR, Balashov D, Bonfim C, Locatelli F, Lankester A, Neven B, and Slatter M
- Subjects
- Humans, Child, Child, Preschool, Female, Male, Infant, Adolescent, Retrospective Studies, Young Adult, Lymphocyte Depletion, Transplantation Conditioning methods, HLA Antigens immunology, Adult, Treatment Outcome, Infant, Newborn, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation methods, Cyclophosphamide therapeutic use, Cyclophosphamide administration & dosage, Receptors, Antigen, T-Cell, alpha-beta, Antigens, CD19, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control
- Abstract
Abstract: HLA-mismatched transplants with either in vitro depletion of CD3+ T-cell receptor (TCR)αβ/CD19 (TCRαβ) cells or in vivo T-cell depletion using posttransplant cyclophosphamide (PTCY) have been increasingly used for patients with inborn errors of immunity (IEIs). We performed a retrospective multicenter study via the EBMT registry on 306 children with IEIs undergoing their first transplant between 2010 and 2019 from an HLA-mismatched donor using TCRαβ (n = 167) or PTCY (n = 139). The median age for hematopoietic stem cell transplantation (HSCT) was 1.2 years (range, 0.03-19.6 years). The 3-year overall survival (OS) was 78% (95% confidence interval (CI), 71-84) after TCRαβ and 66% (57-74) after PTCY (P = .013). Pre-HSCT morbidity score (hazard ratio [HR], 2.27; 1.07-4.80, P = .032) and non-busulfan/treosulfan conditioning (HR, 3.12; 1.98-4.92, P < .001) were the only independent predictors of unfavorable OS. The 3-year event-free survival (EFS) was 58% (50%-66%) after TCRαβ and 57% (48%-66%) after PTCY (P = .804). The cumulative incidence of severe acute graft-versus-host disease (GvHD) was higher after PTCY (15%, 9%-21%) than TCRαβ (6%, 2%-9%, P = .007), with no difference in chronic GvHD (PTCY, 11%, 6%-17%; TCRαβ, 7%, 3%-11%, P = .173). The 3-year GvHD-free EFS was 53% (44%-61%) after TCRαβ and 41% (32%-50%) after PTCY (P = .080). PTCY had significantly higher rates of veno-occlusive disease (14.4% vs TCRαβ 4.9%, P = .009), acute kidney injury (12.7% vs 4.6%, P = .032), and pulmonary complications (38.2% vs 24.1%, P = .017). Adenoviremia (18.3% vs PTCY 8.0%, P = .015), primary graft failure (10% vs 5%, P = .048), and second HSCT (17.4% vs 7.9%, P = .023) were significantly higher in TCRαβ. In conclusion, this study demonstrates that both approaches are suitable options in patients with IEIs, although they are characterized by different advantages and outcomes., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
- Published
- 2024
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