Filgrastim enhances T-cell clearance by antithymocyte globulin exposure after unrelated cord blood transplantation
Autor: | Julie-Anne Gabelich, Jaap Jan Boelens, Rick Admiraal, Jurgen Langenhorst, Jürgen Kuball, Coco de Koning, Stefan Nierkens |
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Rok vydání: | 2018 |
Předmět: |
Male
endocrine system medicine.medical_specialty Adolescent Filgrastim T-Lymphocytes T cell Cord Blood Stem Cell Transplantation Granulocyte behavioral disciplines and activities Gastroenterology Lymphocyte Depletion Young Adult 03 medical and health sciences 0302 clinical medicine Internal medicine mental disorders medicine Humans Child Antilymphocyte Serum Bone Marrow Transplantation Retrospective Studies Transplantation Thymoglobulin business.industry Infant Hematology Haematopoiesis surgical procedures operative medicine.anatomical_structure Child Preschool 030220 oncology & carcinogenesis Cord blood Female Bone marrow business 030215 immunology medicine.drug |
Zdroj: | Blood Advances, 2(5), 565. The American Society of Hematology |
ISSN: | 2473-9537 2473-9529 |
Popis: | Residual antithymocyte globulin (ATG; Thymoglobulin) exposure after allogeneic hematopoietic (stem) cell transplantation (HCT) delays CD4+T-cell immune reconstitution (CD4+IR), subsequently increasing morbidity and mortality. This effect seems particularly present after cord blood transplantation (CBT) compared to bone marrow transplantation (BMT). The reason for this is currently unknown. We investigated the effect of active-ATG exposure on CD4+IR after BMT and CBT in 275 patients (CBT n = 155, BMT n = 120; median age, 7.8 years; range, 0.16-19.2 years) receiving their first allogeneic HCT between January 2008 and September 2016. Multivariate log-rank tests (with correction for covariates) revealed that CD4+IR was faster after CBT than after BMT with 10 active-ATG × day/mL exposure severely impaired CD4+IR after CBT (P< .001), but not after BMT (P= .74). To decipher these differences, we performed ATG-binding and ATG-cytotoxicity experiments using cord blood- and bone marrow graft-derived T-cell subsets, B cells, natural killer cells, and monocytes. No differences were observed. Nevertheless, a major covariate in our cohort was Filgrastim treatment (only given after CBT). We found that Filgrastim (granulocyte colony-stimulating factor [G-CSF]) exposure highly increased neutrophil-mediated ATG cytotoxicity (by 40-fold [0.5 vs 20%;P= .002]), which explained the enhanced T-cell clearance after CBT. These findings imply revision of the use (and/or timing) of G-CSF in patients with residual ATG exposure. |
Databáze: | OpenAIRE |
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