title: Inflammatory (B) symptoms are independent predictors of myelosuppression from chemotherapy in Non-Hodgkin Lymphoma (NHL) patients--analysis of data from a British National Lymphoma Investigation phase III trial comparing CHOP to PMitCEBO.
abstract: BACKGROUND
  Toxicity from chemotherapy is highly variable, unpredictable and results in substantial morbidity and increased healthcare costs. New predictors of toxicity are required to improve the safety and efficacy of chemotherapy. Inflammatory or B symptoms in lymphoma are associated with elevated plasma inflammatory markers and predict worse treatment response and survival. Recent data suggest that systemic inflammation results in reduced hepatic drug metabolism and increased toxicity from chemotherapy. We investigated whether B symptoms were associated with greater toxicity in patients treated for non-Hodgkin lymphoma (NHL).
  
  
  METHODS
  The British National Lymphoma Investigation compared two chemotherapy regimens in older patients with aggressive NHL. Approximately 50% of patients had B symptoms. Demographic and toxicity data on 664 patients were analysed to identify predictors of toxicity by multivariate analysis, with particular reference to B symptoms.
  
  
  RESULTS
  Using univariate analyses, severe (grades 3-4) leucopenia, anaemia, thrombocytopenia, nausea and vomiting and diarrhoea occurred more frequently in patients with B symptoms. The associations between B symptoms and severe leucopenia (OR 1.7, p = 0.005) and anaemia (OR 2.3, p = 0.025) persisted after adjustment for other prognostic factors in multivariate analyses. The use of granulocyte colony stimulating factor reduced neutropenia in patients with both A and B symptoms.
  
  
  CONCLUSIONS
  For the first time and in a large NHL cohort we have shown that inflammatory symptoms are independent predictors for myelosuppression from chemotherapy. These data will enable improved prognostication for toxicity and provide individualization of therapy in NHL and other tumours. These findings also create the potential for strategies used prior to chemotherapy aimed at reducing systemic inflammation in order to improve drug metabolism and reduce treatment-related toxicity.
authors.affiliation: 1Imperial College, London, UK. r.sharma@imperial.ac.uk
authors.forename: Rohini
authors.initials: R
authors.lastname: Sharma
authors.forename: David
authors.initials: D
authors.lastname: Cunningham
authors.forename: Paul
authors.initials: P
authors.lastname: Smith
authors.forename: Graham
authors.initials: G
authors.lastname: Robertson
authors.forename: Owen
authors.initials: O
authors.lastname: Dent
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Clarke
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001761:Bleomycin / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D005047:Etoposide / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007970:Leukopenia / Q000188:drug therapy* / Q000276:immunology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000009:adverse effects / Q000627:therapeutic use; D011239:Prednisolone / Q000009:adverse effects / Q000627:therapeutic use; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D011994:Recombinant Proteins; D016896:Treatment Outcome; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D011994:Recombinant Proteins; D001761:Bleomycin; D016179:Granulocyte Colony-Stimulating Factor; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone; D008942:Mitoxantrone; D011241:Prednisone