title: Treatment of aggressive B-cell lymphoma in elderly patients: influence of single nucleotide polymorphisms affecting pharmacodynamics of chemotherapeutics.
abstract: Clinical and/or biological risk factors are needed to identify elderly patients with aggressive B-cell lymphoma able to receive full-dose R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) treatment. We present a retrospective analysis of 83 patients≥75 years of age (range: 75-97) who were diagnosed with aggressive B cell lymphoma between 2004 and 2011 in our clinic. R-CHOP-like therapy was administered in 82% of these patients resulting in a median overall survival of 54 months. A median cumulative dose of 226 mg/m2 doxorubicin and a median of six cycles were applied in these patients. Two genotypes of the CBR3 and MLH1 genes affecting the metabolism of cytostatics identified a subgroup with a favorable prognosis (median overall survival not reached vs. 30 months, p=0.01). A treatment strategy aiming at full-dose R-CHOP was feasible and resulted in an encouraging treatment outcome in patients≥75 years. Pharmacogenetic parameters, if independently validated, may be helpful in elderly patients.
authors.affiliation: Department of Internal Medicine III with Hematology, Medical Oncology, Hemostaseology, Infectious Disease, Rheumatology, Oncologic Center, Laboratory for Immunological and Molecular Cancer Research, Paracelsus Medical University Salzburg , Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Melchardt
authors.forename: Lukas
authors.initials: L
authors.lastname: Weiss
authors.forename: Clemens
authors.initials: C
authors.lastname: Hufnagl
authors.forename: Daniel
authors.initials: D
authors.lastname: Neureiter
authors.forename: Ralf
authors.initials: R
authors.lastname: Kemmerling
authors.forename: Patrick
authors.initials: P
authors.lastname: Morre
authors.forename: Ann
authors.initials: A
authors.lastname: Boekstegers
authors.forename: Georg
authors.initials: G
authors.lastname: Hopfinger
authors.forename: Jutta
authors.initials: J
authors.lastname: Auberger
authors.forename: Susanne
authors.initials: S
authors.lastname: Steinkirchner
authors.forename: Lisa
authors.initials: L
authors.lastname: Pleyer
authors.forename: Richard
authors.initials: R
authors.lastname: Greil
authors.forename: Alexander
authors.initials: A
authors.lastname: Egle
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D000429:Alcohol Oxidoreductases / Q000235:genetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D005838:Genotype; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011379:Prognosis; D012189:Retrospective Studies; D000069283:Rituximab / Q000008:administration & dosage; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D000429:Alcohol Oxidoreductases; C531130:CBR3 protein, human; D000070957:MutL Protein Homolog 1; D011241:Prednisone
keywords: Aggressive lymphoma; R-CHOP; elderly; single nucleotide polymorphisms; toxicity