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

Thomas Melchardt; Lukas Weiss; Clemens Hufnagl; Daniel Neureiter; Ralf Kemmerling; Patrick Morre; Ann Boekstegers; Georg Hopfinger; Jutta Auberger; Susanne Steinkirchner; Lisa Pleyer; Richard Greil; Alexander Egle

doi:10.3109/10428194.2014.916798

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.

Authors

Thomas Melchardt¹, Lukas Weiss, Clemens Hufnagl, Daniel Neureiter, Ralf Kemmerling, Patrick Morre, Ann Boekstegers, Georg Hopfinger, Jutta Auberger, Susanne Steinkirchner, Lisa Pleyer, Richard Greil, Alexander Egle

Affiliation

¹ 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.

PMID: 24798743
DOI: 10.3109/10428194.2014.916798

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