Finding a balance in reduced toxicity hematopoietic stem cell transplantation for thalassemia: role of infused CD3+ cell count and immunosuppression.

Autor: Meissner B; Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany. Meissner.Barbara@mh-hannover.de., Lang P; Department Hematology/Oncology, University Children's Hospital Tuebingen, Tuebingen, Germany., Bader P; Department for Children and Adolescents, Division for Stem Cell Transplantation, Immunology and Intensive Care Medicine, Goethe University Frankfurt, University Hospital, Frankfurt, Germany., Hoenig M; Department of Pediatrics, University Medical Center Ulm, Ulm, Germany., Müller I; Division of Pediatric Stem Cell Transplantation and Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Meisel R; Devision of Pediatric Stem Cell Therapy, Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany., Greil J; University Children's Hospital Heidelberg, Heidelberg, Germany., Sauer MG; Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany., Metzler M; Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Erlangen, Germany., Corbacioglu S; Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany., Burkhardt B; Pediatric Hematology and Oncology, University Hospital Muenster, Muenster, Germany., Wölfl M; University Children's Hospital Wuerzburg, Wuerzburg, Germany., Strahm B; Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Kafa K; Pediatric Hematology and Oncology, Martin Luther University Halle-Wittenberg, Halle, Germany., Basu O; University Children's Hospital Essen, Essen, Germany., Lode HN; Department of Pediatric Oncology and Hematology, University Medicine Greifswald, Greifswald, Germany., Gruhn B; Department of Pediatrics, Jena University Hospital, Jena, Germany., Cario H; Department of Pediatrics, University Medical Center Ulm, Ulm, Germany., Ozga AK; Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Zimmermann M; Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany., Jarisch A; Department for Children and Adolescents, Division for Stem Cell Transplantation, Immunology and Intensive Care Medicine, Goethe University Frankfurt, University Hospital, Frankfurt, Germany., Beier R; Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
Jazyk: angličtina
Zdroj: Bone marrow transplantation [Bone Marrow Transplant] 2024 May; Vol. 59 (5), pp. 587-596. Date of Electronic Publication: 2024 Feb 07.
DOI: 10.1038/s41409-024-02219-0
Abstrakt: We performed a retrospective analysis on 124 patients with transfusion-dependent thalassemia who were registered in the German pediatric registry for stem cell transplantation. All patients underwent first allogeneic hematopoietic stem cell transplantation (HSCT) between 2011 and 2020 and belonged mainly to Pesaro risk class 1-2. Four-year overall (OS) and thalassemia-free survival (TFS) were 94.5% ± 2.9% and 88.0% ± 3.4% after treosulfan-fludarabine-thiotepa- and 96.9% ± 3.1% (P = 0.763) and 96.9% ± 3.1% (P = 0.155) after busulfan-fludarabine-based conditioning. Mixed chimerism below 75% occurred predominantly in treosulfan-based regimens (27.5% versus 6.2%). OS and TFS did not differ significantly between matched sibling, other matched family and matched unrelated donor (UD) HSCTs (OS: 100.0%, 100.0%, 96.3% ± 3.6%; TFS: 96.5% ± 2.4%, 90.0% ± 9.5%, 88.9% ± 6.0%). However, mismatched UD-HSCTs performed less favorable (OS: 84.7% ± 7.3% (P = 0.029); TFS: 79.9% ± 7.4% (P = 0.082)). We generated a scoring system reflecting the risk to develop mixed chimerism in our cohort. The main risk-reducing factors were a high CD3+ cell count (≥6 × 10 7 /kg) in the graft, busulfan-conditioning, pre-conditioning therapy and low-targeted ciclosporin A trough levels. Acute GvHD grade III-IV in treosulfan-based concepts predominantly occurred in patients with UD and reduced GvHD prophylaxis but not in the context of high CD3+ cell doses. Taken together, this information might be used to develop more risk-adapted HSCT regimens for thalassemia patients.
(© 2024. The Author(s).)
Databáze: MEDLINE
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