title: Role of glutathione-S-transferase (GST) polymorphisms in patients with advanced Hodgkin lymphoma: results from the HD2000 GISL trial.
abstract: Polymorphisms of the Glutathione-S Transferase (GST) family may influence the prognosis in lymphoma patients. We aimed to validate the impact of GSTT1 and GSTM1 deletions and of the GSTP1Ile105Val polymorphism on outcome and toxicity in 140 patients with advanced Hodgkin's lymphoma enrolled in the prospective multicenter HD2000-GISL trial, comparing ABVD, BEACOPP and CEC regimens. Carriers of the GSTP1Ile105Val polymorphism had a higher rate of grade 3-4 anemia following treatment. Overall, our study failed to validate GST genotyping as prognostic factor for progression-free survival (PFS). Only the small cohort of patients with an international prognostic score (IPS) >3 and undeleted GSTT1 and/or GSTM1, treated with ABVD had worse progression-free survival (PFS) (GSTT1 + vs GSTT1-: HR 5.02, 95% C.I., 1.16-21.8, p = 0.031, GSTM1 + /GSTT1 + vs GSTM1-and/or GSTT1-: HR 4.61, 95% C.I. 1.28- 16.6, p = 0.019, respectively). No differences were observed for patients treated with intensified regimens, as BEACOPP and CEC. In conclusion, the prognostic role of GST polymorphism, if at all, is limited to a small subgroup of patients treated with standard ABVD regimen.
authors.affiliation: UOC di Ematologia, Dipartimento Oncoematologico, Azienda Ospedaliera, Cosenza, Italy. fortunato_morabito@tin.it
authors.forename: Fortunato
authors.initials: F
authors.lastname: Morabito
authors.forename: Stefan
authors.initials: S
authors.lastname: Hohaus
authors.forename: Corrado
authors.initials: C
authors.lastname: Mammi
authors.forename: Luigi
authors.initials: L
authors.lastname: Marcheselli
authors.forename: Massimo
authors.initials: M
authors.lastname: Gentile
authors.forename: Francesco
authors.initials: F
authors.lastname: Merli
authors.forename: Antonella
authors.initials: A
authors.lastname: Montanini
authors.forename: Caterina
authors.initials: C
authors.lastname: Stelitano
authors.forename: Antonio
authors.initials: A
authors.lastname: La Sala
authors.forename: Renato
authors.initials: R
authors.lastname: Scalone
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Voso
authors.forename: Stefano
authors.initials: S
authors.lastname: Luminari
authors.forename: Emilio
authors.initials: E
authors.lastname: Iannitto
authors.forename: Paolo
authors.initials: P
authors.lastname: Gobbi
authors.forename: Massimo
authors.initials: M
authors.lastname: Federico
mesh_terms: D000328:Adult; D000740:Anemia / Q000139:chemically induced / Q000235:genetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001711:Biotransformation / Q000235:genetics; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics* / Q000502:physiology; D005982:Glutathione Transferase / Q000235:genetics* / Q000502:physiology; D006689:Hodgkin Disease / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000401:mortality; D006801:Humans; D008130:Lomustine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D011344:Procarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D011379:Prognosis; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D014751:Vindesine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D001761:Bleomycin; D016190:Carboplatin; D003520:Cyclophosphamide; D003606:Dacarbazine; D004317:Doxorubicin; D015251:Epirubicin; D005047:Etoposide; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D008130:Lomustine; D009363:Neoplasm Proteins; D011241:Prednisone; D011344:Procarbazine; D014747:Vinblastine; D014750:Vincristine; D014751:Vindesine; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human