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Role of Pharmacogenetics in Hematopoietic Stem Cell Transplantation Outcome in Children.

ABSTRACT: Hematopoietic stem cell transplantation (HSCT) is an established therapeutic procedure for several congenital and acquired disorders, both malignant and nonmalignant. Despite the great improvements in HSCT clinical practices over the last few decades, complications, such as graft vs. host disease (GVHD) and sinusoidal obstructive syndrome (SOS), are still largely unpredictable and remain the major causes of morbidity and mortality. Both donor and patient genetic background might influence the success of bone marrow transplantation and could at least partially explain the inter-individual variability in HSCT outcome. This review summarizes some of the recent studies on candidate gene polymorphisms in HSCT, with particular reference to pediatric cohorts. The interest is especially focused on pharmacogenetic variants affecting myeloablative and immunosuppressive drugs, although genetic traits involved in SOS susceptibility and transplant-related mortality are also reviewed.

SUBMITTER: Franca R

PROVIDER: S-EPMC4581262 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Role of Pharmacogenetics in Hematopoietic Stem Cell Transplantation Outcome in Children.

Franca Raffaella R Stocco Gabriele G Favretto Diego D Giurici Nagua N Decorti Giuliana G Rabusin Marco M

International journal of molecular sciences 20150810 8

Hematopoietic stem cell transplantation (HSCT) is an established therapeutic procedure for several congenital and acquired disorders, both malignant and nonmalignant. Despite the great improvements in HSCT clinical practices over the last few decades, complications, such as graft vs. host disease (GVHD) and sinusoidal obstructive syndrome (SOS), are still largely unpredictable and remain the major causes of morbidity and mortality. Both donor and patient genetic background might influence the su ...[more]

PMID: 26266406

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Project description:BackgroundGastrointestinal tract function and it's integrity are controlled by a number of peptides whose secretion is influenced by severe inflammation. In stomach the main regulatory peptide is ghrelin. For upper small intestine cholecystokinin and lower small intestine glucagon-like peptide- 1 are secreted, while fibroblast growth factor-21 is secreted by several organs, including the liver, pancreas, and adipose tissue [12]. Hematopoietic stem cell transplantation causes serious mucosal damage, which can reflect on this peptides.MethodsThe aim of the study was to determine fasting plasma concentrations of ghrelin, cholecystokinin, glucagon- like peptide-1, and fibroblast growth factor-21, and their gene expressions, before and 6 months after hematopoietic stem cell transplantation.27 children were studied, control group included 26 healthy children.ResultsAcute graft versus host disease was diagnosed in 11 patients (41%, n = 27). Median pre-transplantation concentrations of gastrointestinal peptides, as well as their gene expressions, were significantly lower in studied group compared with the control group. Only median of fibroblast growth factor-21 concentration was near-significantly higher before stem cell transplantation than in the control group. The post-hematopoietic transplant results revealed significantly higher concentrations of the studied peptides (except fibroblast growth factor-21) and respective gene expressions as compare to pre transplant results. Median glucagone like peptide-1 concentrations were significantly decreased in patients with features of acute graft versus host disease. Moreover, negative correlation between glucagone like peptide-1 concentrations and acute graft versus host disease severity was found.ConclusionsIncreased concentrations and gene expressions of gastrointestinal tract regulation peptides can be caused by stimulation of regeneration in the severe injured organ. Measurement of these parameters may be a useful method of assessment of severity of gastrointestinal tract complications of hematopoietic stem cell transplantation.

Dataset Information

Role of Pharmacogenetics in Hematopoietic Stem Cell Transplantation Outcome in Children.

Publications

Role of Pharmacogenetics in Hematopoietic Stem Cell Transplantation Outcome in Children.

Similar Datasets

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