title: Pharmacogenetic analysis in the treatment of Hodgkin lymphoma.
abstract: About 15-20% of patients with Hodgkin lymphoma (HL) treated with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy ± radiotherapy still die following relapse or progressive disease. The outcome might be influenced by gene polymorphisms influencing chemotherapy metabolism. We studied 126 patients with HL treated with the ABVD regimen. We analyzed glutathione S-transferases (GSTT1, GSTM1 and GSTP1), cytochromes P450 (CYP3A4 and CYP2D6), UGT1A1 and BLMH gene polymorphisms and their association with clinical and outcome variables. Patients with a GSTM1 genotype associated with extensive or ultrahigh activity had a probability of 93.8% to achieve a complete response, while the remainder of the patients had a probability of 82.3% (p = 0.04). This variable maintained its statistical significance in multivariate analysis (hazard ratio 3.7, 95% confidence interval 1-13, p = 0.05). Patients with an extensive or ultrahigh GSTM1 genotype had better prognostic factors than those with poor or intermediate genotypes (hemoglobin level, p = 0.003; serum albumin, p = 0.05; and International Prognostic Score, p = 0.038). Thus, in the treatment of HL, clinical determinants might be more relevant than the pharmacogenetic parameters analyzed to date.
authors: Department of Hematology, Althaia, Universitat Internacional de Catalunya, Manresa, Spain.
authors: Albert
authors: A
authors: Altés
authors: Laia
authors: L
authors: Paré
authors: Albert
authors: A
authors: Esquirol
authors: Blanca
authors: B
authors: Xicoy
authors: Elena
authors: E
authors: Rámila
authors: Laura
authors: L
authors: Vicente
authors: Rosario
authors: R
authors: López
authors: Jaume
authors: J
authors: Orriols
authors: Ferran
authors: F
authors: Vall-llovera
authors: Blanca
authors: B
authors: Sánchez-González
authors: Elisabeth
authors: E
authors: del Río
authors: Anna
authors: A
authors: Sureda
authors: David
authors: D
authors: Páez
authors: Montserrat
authors: M
authors: Baiget
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006689:Hodgkin Disease / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D011878:Radiotherapy / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase