Influence of ATLG serum levels on CD3/CD19-depleted hematopoietic grafts and on immune recovery in pediatric haplo-HSCT.

Autor:	Maier CP; Department of General Pediatrics, Hematology/Oncology, Children's University Hospital Tuebingen, Tuebingen, Germany.; Department of Hematology, Oncology, Clinical Immunology and Rheumatology, Center for Internal Medicine, University Hospital Tuebingen, Tuebingen, Germany., Klose C; Center for Clinical Transfusion Medicine, University Hospital Tuebingen, Tuebingen, Germany., Seitz CM; Department of General Pediatrics, Hematology/Oncology, Children's University Hospital Tuebingen, Tuebingen, Germany.; German Cancer Consortium (DKTK), Partner Site Tuebingen, a partnership between DKFZ and University Hospital Tuebingen, Tuebingen, Germany.; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies,' University of Tuebingen, Tuebingen, Germany., Heubach F; Department of General Pediatrics, Hematology/Oncology, Children's University Hospital Tuebingen, Tuebingen, Germany.; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies,' University of Tuebingen, Tuebingen, Germany., Döring M; Department of General Pediatrics, Hematology/Oncology, Children's University Hospital Tuebingen, Tuebingen, Germany., Meisel R; Division of Pediatric Stem Cell Therapy, Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany., Schuster F; Division of Pediatric Stem Cell Therapy, Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany., Gruhn B; Department of Pediatrics, Jena University Hospital, Jena, Germany., Keller F; Department of Nephrology, Center for Internal Medicine, University Hospital Ulm, Ulm, Germany.; Institute of Experimental and Clinical Pharmacology and Toxicology, University Hospital Ulm, Ulm, Germany., Rabsteyn A; Department of General Pediatrics, Hematology/Oncology, Children's University Hospital Tuebingen, Tuebingen, Germany.; German Cancer Consortium (DKTK), Partner Site Tuebingen, a partnership between DKFZ and University Hospital Tuebingen, Tuebingen, Germany.; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies,' University of Tuebingen, Tuebingen, Germany., Arendt AM; Department of General Pediatrics, Hematology/Oncology, Children's University Hospital Tuebingen, Tuebingen, Germany., Amorelli G; Department of General Pediatrics, Hematology/Oncology, Children's University Hospital Tuebingen, Tuebingen, Germany.; German Cancer Consortium (DKTK), Partner Site Tuebingen, a partnership between DKFZ and University Hospital Tuebingen, Tuebingen, Germany.; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies,' University of Tuebingen, Tuebingen, Germany., Eichholz T; Department of General Pediatrics, Hematology/Oncology, Children's University Hospital Tuebingen, Tuebingen, Germany., Feuchtinger T; Department of Pediatric Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Dr. von Hauner Children's University Hospital, Munich, Germany., Martinius H; Neovii Biotech, Graefelfing, Germany., Nierkens S; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Teltschik R; Department of General Pediatrics, Hematology/Oncology, Children's University Hospital Tuebingen, Tuebingen, Germany., Schulte JH; Department of General Pediatrics, Hematology/Oncology, Children's University Hospital Tuebingen, Tuebingen, Germany.; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies,' University of Tuebingen, Tuebingen, Germany., Lengerke C; Department of Hematology, Oncology, Clinical Immunology and Rheumatology, Center for Internal Medicine, University Hospital Tuebingen, Tuebingen, Germany., Handgretinger R; Department of General Pediatrics, Hematology/Oncology, Children's University Hospital Tuebingen, Tuebingen, Germany., Lang P; Department of General Pediatrics, Hematology/Oncology, Children's University Hospital Tuebingen, Tuebingen, Germany.; German Cancer Consortium (DKTK), Partner Site Tuebingen, a partnership between DKFZ and University Hospital Tuebingen, Tuebingen, Germany.; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies,' University of Tuebingen, Tuebingen, Germany.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2024 May 14; Vol. 8 (9), pp. 2160-2171.
DOI:	10.1182/bloodadvances.2023011016
Abstrakt:	Abstract: Anti-T lymphocyte globulin (ATLG) significantly reduces the risk of engraftment failure in allogeneic hematopoietic stem cell transplant (HSCT) but hampers posttransplant immune reconstitution. We hypothesized that in patients receiving haploidentical CD3/CD19-depleted grafts, these double-edged effects could be better balanced by attaining high ATLG serum concentrations before transplant but as low as possible on the day of transplant. Therefore, we moved the start of ATLG application to day -12 and determined serum concentrations of T-cell-specific ATLG in pediatric patients treated with 3 established dosing regimens (15, 30, or 60 mg/kg). Corresponding mean T-cell-specific ATLG serum concentrations at day 0 were 1.14, 2.99, or 12.10 μg/mL, respectively. Higher ATLG doses correlated with higher peak levels at days -8 and -7 and reduced graft rejection, whereas lower ATLG doses correlated with significantly faster posttransplant recovery of T and natural killer cells. The rate of graft-versus-host disease remained low, independent of ATLG doses. Moreover, in vitro assays showed that ATLG concentrations of 2.0 μg/mL and lower only slightly reduced the activity of natural killer cells, and therefore, the function of such effector cells might be preserved in the grafts. Pharmacokinetic analysis, compatible with linear first-order kinetics, revealed similar half-life values, independent of ATLG doses. Hence, the day on which a desired ATLG serum level is reached can be calculated before HSCT. Our retrospective study demonstrates the relevance of dosing and time of administration of ATLG on engraftment and immune recovery in ex vivo CD3/CD19-depleted haploidentical HSCT. (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu