BMC Cancer 2009, 9:153 http://www.biomedcentral.com/1471-2407/9/153 Table 2: Overall toxicity from chemotherapy in selected cohort. Category Number (%) N = 664 Variable Anaemia stage Leucopenia stage Thrombocytopenia Mucositis Nausea/vomiting Diarrhoea Neuropathy Skin rash 0 1 2 3 4 0 1 2 3 4 0 1 2 3 4 0 1 2 3 4 No data 0 1 2 3 4 No data 0 1 2 3 4 No data 0 1 2 3 4 No data 0 1 2 3 4 No data 116 (17.5) 241 (36.3) 259 (39.0) 39 (5.9) 9 (1.4) 171 (25.8) 70 (10.5) 96 (14.5) 154 (23.2) 173 (26.1) 503 (75.8) 51 (7.7) 45 (6.8) 33 (5.0) 32 (4.8) 347 (52.3) 137 (20.6) 98 (14.8) 17 (2.6) 3 (0.5) 62 (9.3) 329 (49.5) 168 (25.3) 68 (10.2) 39 (5.9) 5 (0.8) 55 (8.3) 434 (65.4) 74 (11.1) 50 (7.5) 45 (6.8) 7 (1.1) 54 (8.1) 318 (47.9) 192 (28.9) 77 (11.6) 26 (3.9) 0 51 (7.7) 521 (78.5) 50 (7.5) 27 (4.1) 7 (1.1) 2 (0.3) 57 (8.6) iting (21% vs 15%) and diarrhoea (21% vs 12%) were significantly more common among patients with B symp- toms (Table 6). However the associations between B symptoms and nausea and vomiting and diarrhoea disap- peared after adjustment for other variables independently associated with these symptoms (Table 7). Response and survival There was no statistically significant difference in either response rates or survival for patients with or without B symptoms. Discussion These data demonstrate for the first time and in a large patient cohort that the presence of inflammatory (B) symptoms is an independent predictor of increased inci- dence of severe leucopenia and anaemia in patients with malignancy, in this case high risk, intermediate grade non-Hodgkin lymphoma. Although B symptoms were associated with an increased risk of thrombocytopenia, nausea and vomiting and diarrhoea on univariate analy- sis, these associations were not supported on multivariate analysis. The study has some limitations. Firstly, it was an unplanned reanalysis of prospectively collected data, and the presence of inflammation was only assessed clinically as correlative blood samples for measurement of inflam- matory proteins were not available. In addition, it was not possible to assess the impact of B symptoms on the inci- dence of neutropenia, febrile neutropenia, toxicity related hospitalisation, treatment related death and dose delay or reduction, as these data had not been reliably recorded. Such associations and correlation with plasma inflamma- tory markers should be evaluated in future studies. How- ever, an 18% increase (40% vs 58%) in the incidence of grades 3 and 4 leucopenia, which was worse in patients with inflammatory symptoms is highly clinically signifi- cant and likely to impact on such outcomes. This study was principally undertaken to provide a clinical "proof of principle" of our previous pre-clinical and clini- cal findings that the presence of an inflammatory response predicts for slower hepatic clearance of cytotoxic drugs and increased toxicity. The data will not have a major immediate impact on the management of patients with NHL, as prophylactic G-CSF is already routinely used in this condition, and our data confirm that this provides a protective effect against leucopenia. Also, in this cohort, the presence of inflammatory symptoms did not adversely impact on survival, which again raises questions about the immediate clinical significance of our findings. However, this may have been due in part to our desire to include only patients on whom full data sets were available for the assessment of toxicity and could have excluded patients Page 5 of 10 (page number not for citation purposes)