Treatment of aggressive B-cell lymphoma in elderly patients: influence of single nucleotide polymorphisms affecting pharmacodynamics of chemotherapeutics

Leuk Lymphoma. 2015 Feb;56(2):353-60. doi: 10.3109/10428194.2014.916798. Epub 2014 Jun 25.

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.

Keywords: Aggressive lymphoma; R-CHOP; elderly; single nucleotide polymorphisms; toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Aged
  • Aged, 80 and over
  • Alcohol Oxidoreductases / genetics
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Drug Administration Schedule
  • Female
  • Genotype
  • Humans
  • Leukopenia / chemically induced
  • Lymphoma, B-Cell / drug therapy*
  • Lymphoma, B-Cell / genetics*
  • Lymphoma, B-Cell / pathology
  • Male
  • MutL Protein Homolog 1
  • Nuclear Proteins / genetics
  • Polymorphism, Single Nucleotide*
  • Prednisone / administration & dosage
  • Prednisone / adverse effects
  • Prognosis
  • Retrospective Studies
  • Rituximab / administration & dosage
  • Survival Analysis
  • Treatment Outcome
  • Vincristine / administration & dosage
  • Vincristine / adverse effects

Substances

  • Adaptor Proteins, Signal Transducing
  • MLH1 protein, human
  • Nuclear Proteins
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Alcohol Oxidoreductases
  • CBR3 protein, human
  • MutL Protein Homolog 1
  • Prednisone