Analysis of glutathione S-transferase and cytochrome P450 gene polymorphism in recipients of dose-adjusted busulfan-cyclophosphamide conditioning.
Int J Hematol
; 111(1): 84-92, 2020 Jan.
Article
in En
| MEDLINE
| ID: mdl-31555969
ABSTRACT
Sporadic incidence of veno-occlusive disease (VOD) continues to occur, despite achievement of recommended busulfan (BU) concentrations after real-time BU dose adjustment. To explore the potential influence of glutathione S-transferase (GST) and cytochrome P450 (CYP) genotypes on plasma BU concentration, subsequent VOD, and transplant outcome, we assessed the polymorphisms of multiple GST and CYP genes. Fifty-five patients were included (median age 38 years; range 21-67). Of these, 49 received dose-adjusted BU/CY therapy. Twenty-six patients received transplants from human leukocyte antigen-identical siblings, 26 from unrelated donors. The GSTA1*A/*A genotype was significantly associated with lower BU first-dose area under curve (AUC1st). We found that patients with higher AUC1st showed a significantly higher serum total bilirubin during the first month after transplantation, but this was not necessarily associated with subsequent development of VOD. We further analyzed a possible association of GST and CYP polymorphisms and VOD development, and found none of the polymorphisms investigated was associated with VOD incidence. Regarding transplant outcomes, GSTM1-positive patients showed lower relapse rates and better overall survival in multivariate analyses. These results suggest that a GSTM1-positive genotype in patients receiving BU/CY conditioning protects against relapse of hematological malignancies after allogeneic hematopoietic stem cell transplantation.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Hepatic Veno-Occlusive Disease
/
Busulfan
/
Hematologic Neoplasms
/
Cyclophosphamide
/
Cytochrome P-450 Enzyme System
/
Glutathione Transferase
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
Asia
Language:
En
Journal:
Int J Hematol
Journal subject:
HEMATOLOGIA
Year:
2020
Document type:
Article
Affiliation country:
Japan