1. Impact of early cyclosporine A levels on acute graft-versus-host disease in allogeneic hematopoietic stem cell transplantation using in vivo T-cell depletion.
- Author
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Nikoloudis A, Buxhofer-Ausch V, Aichinger C, Binder M, Hasengruber P, Kaynak E, Wipplinger D, Milanov R, Strassl I, Stiefel O, Machherndl-Spandl S, Petzer A, Weltermann A, and Clausen J
- Subjects
- Humans, Male, Female, Middle Aged, Adult, Retrospective Studies, Lymphocyte Depletion methods, T-Lymphocytes immunology, Immunosuppressive Agents therapeutic use, Adolescent, Aged, Acute Disease, Young Adult, Cyclosporine therapeutic use, Graft vs Host Disease drug therapy, Hematopoietic Stem Cell Transplantation methods, Transplantation, Homologous methods
- Abstract
Background Aims: Cyclosporin A (CsA) remains a major component of immunosuppressive regimens applied in allogeneic hematopoietic stem cell transplantation (HSCT). The impact of CsA trough levels during the first weeks after HSCT has not yet been investigated specifically in anti-T-lymphocyte globulin (ATLG)-based HSCT from matched related and unrelated donors., Methods: To address this issue, we have retrospectively examined 307 consecutive matched related (n = 145) and unrelated (n = 162) HSCTs, using peripheral blood stem cells or bone marrow. HSCTs for active, uncontrolled malignancies were excluded. The initial three weeks' average mean CsA trough levels were analyzed in landmark and multi-state models, using a cut-off of 200 ng/mL., Results: CsA levels >200 ng/mL were associated with a reduced risk of acute graft-versus-host disease (GVHD) grade 3-4 at the first-week landmark (subdistribution hazard ratio [SHR] 0.59, P = 0.03) and the second-week landmark (SHR 0.48, P = 0.004), whereas there was no impact at the third-week landmark (HR 0.87, P = 0.69). This was supported by a multi-state model, in which week 1 (hazard ratio [HR] 0.53, P = 0.006) and week 2 (HR 0.48, P = 0.003), but not week 3 (HR 0.80, P = 0.44) CsA levels >200 ng/mL were associated with a reduced acute GVHD 3-4 risk. Relapse incidence was not significantly affected by week 1 through 3 CsA levels. Despite ATLG's inherent GVHD-preventive properties, week 1 CsA trough levels >200 ng/mL following ATLG-based HSCT (n = 220) were associated with a significantly reduced risk of non-relapse mortality (SHR 0.52, P = 0.02) and improved overall survival (HR 0.61, P = 0.02)., Conclusions: Our findings emphasize the continuing importance of ensuring CsA levels ≥200 ng/mL immediately post-transplant in the setting of ATLG-based HSCT., Competing Interests: Declaration of Competing Interest Dr. Johannes Clausen has received speaker's honoraria and research funding from Neovvii and Novartis. The other authors declare no competing financial interests., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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