Analysis of glutathione S-transferase and cytochrome P450 gene polymorphism in recipients of dose-adjusted busulfan-cyclophosphamide conditioning

Genetic Predictors for Sinusoidal Obstruction Syndrome—A Systematic Review

“…The homozygous deletion of GSTM1 often referred to as “null genotype” was associated with SOS after allogeneic HSCT with a busulfan-based conditioning regimen in pediatric beta-thalassemia patients (OR 4.3, CI 1.5–12.5, p = 0.008) published by Srivastava et al [ 42 ]. This association was not replicated in subsequent studies in predominantly adult [ 36 , 37 , 40 , 52 ] and pediatric cohorts [ 41 , 51 , 54 ], with one pediatric study by Zwaveling et al showing possible evidence of association (no OR reported, p = 0.07) [ 53 ]. The GSTP1 rs1695 (A > G) variant was associated with SOS in a study by Krivoy et al [ 37 ] of 63 adult patients undergoing HSCT for acute myeloid leukemia (no OR reported, p = 0.05) but not in other predominantly adult [ 36 , 40 , 52 ] or pediatric studies [ 51 , 53 , 54 ].…”

“…Twenty-three studies reported on patients who underwent HSCT (85%). Of those, 19 restricted the exposure to allogeneic HSCT (83%), while four also included autologous HSCT (17%) [ 22 , 35 , 36 , 37 ]. Four studies included only HSCT from a sibling donor (17%) [ 38 , 39 , 40 , 41 ], the others included various donor types.…”

“…The study by Curtis et al from 2016 performed a gene–gene interaction study with CTH but also compared the GSTA1 *B*B diplotypes to *A*A/*A*B diplotypes and reported an OR of 10.9 (CI 2.3–51.3) [ 46 ]. The *B haplotype, corresponding to the rs3957357 (C > T) or −69 variant, was not found to be associated with SOS in two studies with 84 and 55 adult patients [ 36 , 52 ], and three pediatric and one mainly adult study with 29 to 77 participants [ 37 , 41 , 53 , 54 ].…”

“…The GSTP1 rs1138272(C > T) variant was tested in two studies and the rs614080 (A > G) variant in one study without showing evidence for an association. The GSTT1 “null genotype” was not associated with SOS in two pediatric [ 42 , 53 ] and four mainly adult [ 36 , 37 , 40 , 52 ] studies. GSTO1 , GSTO2 , and GSTZ1 variants were not found to be associated with SOS [ 36 ].…”

Busulfan-cyclophosphamide versus cyclophosphamide-busulfan as conditioning regimen before allogeneic hematopoietic cell transplantation: a prospective randomized trial

“…The hepatotoxicity of BuCy regimen is well described [12][13][14]26]; one of the pathomechanism of the hepatotoxicity of Bu and Cy is the depletion in glutathione levels, which plays a central role in the metabolism of the toxic metabolites of Cy in hepatocytes [9,10]. Glutathione depletion as a mechanism of hepatic toxicity had been studied extensively [27][28][29]. The precise pathomechanism remains speculative as we do not have data on glutathione metabolism and other explanations are possible.…”