Clinical and In Vitro Studies on Impact of High-Dose Etoposide Pharmacokinetics Prior Allogeneic Hematopoietic Stem Cell Transplantation for Childhood Acute Lymphoblastic Leukemia on the Risk of Post-Transplant Leukemia Relapse

Autor: Maria Chrzanowska, Jacek Wachowiak, Dawid Szpecht, Joanna Sobiak, Dariusz W. Kowalczyk, Urszula Kazimierczak, Mariusz Wysocki, Jan Styczyński
Rok vydání: 2015
Předmět:
Male
Risk
Adolescent
Graft-vs-Leukemia Effect
medicine.medical_treatment
Immunology
Graft vs Leukemia Effect
Hematopoietic stem cell transplantation
Lymphocyte proliferation
In Vitro Techniques
Pharmacology
Disease-Free Survival
Pharmacokinetics
Recurrence
Humans
Transplantation
Homologous
Immunology and Allergy
Medicine
Drug Dosage Calculations
Child
Adverse effect
Th1-Th2 Balance
Childhood Acute Lymphoblastic Leukemia
Cells
Cultured
Etoposide
Cell Proliferation
business.industry
Hematopoietic Stem Cell Transplantation
General Medicine
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Graft versus leukemia
Antineoplastic Agents
Phytogenic
Transplantation
surgical procedures
operative
Female
Original Article
Pediatric acute lymphoblastic leukemia
business
T-Lymphocytes
Cytotoxic
Conditioning
medicine.drug
Zdroj: Archivum Immunologiae et Therapiae Experimentalis
ISSN: 1661-4917
0004-069X
DOI: 10.1007/s00005-015-0343-0
Popis: The impact of etoposide (VP-16) plasma concentrations on the day of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on leukemia-free survival in children with acute lymphoblastic leukemia (ALL) was studied. In addition, the in vitro effects of VP-16 on the lymphocytes proliferation, cytotoxic activity and on Th1/Th2 cytokine responses were assessed. In 31 children undergoing allo-HSCT, VP-16 plasma concentrations were determined up to 120 h after the infusion using the HPLC–UV method. For mentioned in vitro studies, VP-16 plasma concentrations observed on allo-HSCT day were used. In 84 % of children, VP-16 plasma concentrations (0.1–1.5 μg/mL) were quantifiable 72 h after the end of the drug infusion, i.e. when allo-HSCT should be performed. In 20 (65 %) children allo-HSCT was performed 4 days after the end of the drug infusion, and VP-16 was still detectable (0.1–0.9 μg/mL) in plasma of 12 (39 %) of them. Post-transplant ALL relapse occurred in four children, in all of them VP-16 was detectable in plasma (0.1–0.8 μg/mL) on allo-HSCT day, while there was no relapse in children with undetectable VP-16. In in vitro studies, VP-16 demonstrated impact on the proliferation activity of stimulated lymphocytes depending on its concentration and exposition time. The presence of VP-16 in plasma on allo-HSCT day may demonstrate an adverse effect on graft-versus-leukemia (GvL) reaction and increase the risk of post-transplant ALL relapse. Therefore, if 72 h after VP-16 administration its plasma concentration is still above 0.1 μg/mL then the postponement of transplantation for next 24 h should be considered to protect GvL effector cells from transplant material.
Databáze: OpenAIRE
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