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.

Effect of physical exercise on the functional capacity of children and adolescents submitted to transplantation of hematopoietic stem cells—A systematic review with meta-analysis

“…Hematopoietic stem cell transplantation (HSCT) is aimed at restoring the medullary and immunological functions compromised by different clinical situations (Franca et al, 2015; Holtick et al, 2014; Ogonek et al, 2016), such as onco-hematological, autoimmune, metabolic, congenital, hereditary, and some solid tumors (Majhail et al, 2015). According to the World Network for Blood and Bone Marrow Transplantation, there was a progressive increase in the number of transplants performed.…”

Impact of Glutathione S-Transferase Polymorphisms on Busulfan Pharmacokinetics and Outcomes of Hematopoietic Stem Cell Transplantation

“…The target regions for polymorphisms in GSTA1 [G-52A (rs3957356), C-69T (rs3957357), A-513G (rs11964968), T-567G (rs4715332), G-631T (rs4715333), and G-1142C (rs58912740)] and GSTP1 [A313G (rs1695) at codon 105 and C341T (rs1138272) at codon 114] were amplified and sequenced using primers as described previously. 18,19…”

Review of Genetic Variation as a Predictive Biomarker for Chronic Graft-Versus-Host-Disease After Allogeneic Stem Cell Transplantation

“…methylenetetrahydrofolate reductase and thymidylate synthase genotypes have been associated with aGvHD in recipients receiving methotrexate (164). In 2015, a review article by Franca et al (165) summarized studies on pharmacogenetics variants and GvHD in both adult and pediatric cohorts. Despite the observed genotype effects on pharmacokinetic parameters, the studies found no statistically significant effects on cGvHD.…”