Monocytes at the onset, mm 3 X200 14 (27.5) o200 37 (72.5) Platelets at the onset, mm 3 X1 00 000 20 (39.2) o1 00 000 31 (60.8) Uraemia, mg dl 1 p30 19 (43.2) 430 25 (56.8) Stress hyperglycaemiaa No 23 (47.9) Yes 25 (52.1) Stomatitis NCI grade o2 31 (60.8) X2 20 (39.2) MASCC X21 o21 Urinary infection No Yes Productive cough No 34 (66.7) Yes 17 (33.3) Burden of disease Low 18 (35) Moderate 33 (65) 62 (52.1) 57 (47.9) 80 (67.8) 38 (32.2) 94 (80.3) 23 (19.7) 94 (80.3) 23 (19.7) 94 (79.7) 24 (20.3) Characteristics of the febrile neutropaenia episode Abnormal X-ray without pneumonia No 19 (37.3) 88 (73.9) 4.78 Yes 32 (62.7) 31 (26.1) 32 (64) 18 (36) 112 (94) 7 (6) 46 (90.1) 5 (9.9) 112 (91.8) 10 (8.1) 7.9 1.2 OR 95% CI P-value Variable 0.35 0.27 0.73 0.003 0.001 0.7 – 3.7 0.6 – 2.2 2.87 1.41 – 5.86 3.26 1.65 – 6.45 5.37 2.53 – 11.3 o0.0001 4.42 2.14 – 9.19 o0.0001 2.52 1.23 – 5.18 0.010 2.37 – 9.62 o0.0001 3 – 20.5 o0.0001 0.39 – 3.7 0.7 111 (94.1) 7 (5.9) 107 (69) 48 (31) 7.92 3.03 – 20.7 o0.0001 4.3 2.15 – 8 o0.0001 Abbreviations: CI ¼ confidence interval; ECOG ¼ Eastern Cooperative Oncology Group; GCSF ¼ granulocyte-colony stimulating factor; LDH ¼ lactate dehydrogenase; NCI ¼ National Cancer Institute; OR ¼ odds ratio; TNM ¼ tumour-node-metastasis. aStress hyperglycaemia: X121 mg dl 1 (X250 mg m 2 in diabetic patients). group of patients that can be suitable for home treatment, thus making the inclusion of in-patients problematic. We also reasoned that a prognostic model is more helpful to make meaningful decisions in non-obvious situations, such as the assessment of ASPs with subtle clinical signs. According to this clinically oriented approach, we classified our patients into two subgroups that we called ASPs and CUPs, and focused in the prognosis and traits of the former ones. The ASP subgroup British Journal of Cancer (2011) 105(5), 612 – 617 Table 5 (Continued ) Variables Cases, n (%) Controls, n (%) LDH, mU ml 1 o475 X475 Haemoglobin at the onset, gr dl 1 X9 39 (76.4) 102 (83.6) o9 12 (23.6) 19 (16.4) Neutrophils at the onset, mm 3 X100 28 (54.9) 71 (58.1) o100 23 (45.1) 50 (41.9) 1.6 1.1 30 (58.9) 18 (41.1) 81 (66.3) 34 (33.6) 1.42 0.7 – 2.9 C l i n i c a l S t u d i e s 616 Febrile neutropaenia in apparently stable outpatients A Carmona-Bayonas et al ECOG, X2 Chronic bronchitis Chronic heart failure Stomatitis grade, X2 Monocytes, o200 mm 3 Stress hyperglycaemia OR 2.40 4.45 6.47 2.59 2.29 3.06 95% CI 1.03 – 5.55 1.95 – 10.17 1.60 – 26.15 1.15 – 5.81 1.04 – 5.07 1.43 – 6.54 P-value 0.041 o0.0001 0.009 0.02 0.04 0.004 Table 6 Predictive factors for serious complications in the multivariate analysis Abbreviations: CI ¼ confidence interval; ECOG ¼ Eastern Cooperative Oncology Group; OR ¼ odds ratio. represents 80% of our practice in a Medical Oncology unit. We report that this simple classification yields a rate of complications in the range of the MASCC low-risk group. Furthermore, we found that 85% of ASPs were MASCC X21 (low risk), but this model had a lower sensitivity in our population than previously reported. This low performance was suggested by a 64% of patients with complications showing a MASCC index X21. We interpreted this finding as a result of the selection, which defined a different sample to that in which MASCC was validated. The MASCC scale includes eight parameters, and the definition of low risk is a score X21. But when we applied the model to our sample, the reason for the low sensitivity became clear. There are no in-patients, hypotension and invasive fungal infections and the rate of dehydration is low. As a result, these factors become useless to differentiate some cases from others. Only three factors are left to make a prognostic distinction. Although moderate burden of disease, COPD and age 460 years occur more often, they are still relatively infrequent, and thereby they are of limited discrimina- tory help. For our second objective, a retrospective case – control study was considered, as complications are rare events in ASPs. For example, the MASCC Study included 1351 patients, but the derivation set only contained 32 low-risk patients with unexpected complications (Klastersky et al, 2000). Our aim is not to make a comparison with MASCC, but to assess the possibility to further stratify the ASP group, according to the presenting clinical features. Our hypoth- esis is that to reduce uncertainty we need to select not only more homogeneous samples but also to consider different types of variables. In fact, the study proposes that a combination of comorbidities, biological variables and toxicities might improve the prognostic evaluation. The independent variables were ECOG X2, COPD, chronic heart failure, stomatitis grade X2, monocytes o200 mm 3 and hyper- glycaemia. These variables should not be adopted until further investigations could confirm the data and expose new sources of risk. However, all of them have a recognised biological substrate. Several studies have reported that a poor performance status is an adverse prognostic trait (Escalante et al, 1996; Sanz et al, 2002; Talcott et al, 2004; Klastersky et al, 2006). COPD is also a well- known risk factor in FN, as it is associated with serious bacterial infections and acute respiratory failure (Klastersky et al, 2000). The presence of stomatitis can predispose to bacteraemia (Bochud et al, 1994). Moreover, the inability to swallow is one of the causes that justify the hospitalisation (Rubenstein et al, 1993; Mullen et al, 1999; Talcott et al, 2004). Monocytopenia is linked with bacteraemia in children with FN (Rackoff et al, 1996), and early monocytopenia after chemotherapy is correlated with neutro- paenia (Oguz et al, 2006). Finally, hyperglycaemia is common in critically ill patients, in which it is a well-known risk factor of complications (Dandona et al, 2003). Moreover, a randomised trial has shown that intensive insulin therapy reduces morbidity and mortality in this setting (Van den Berghe et al, 2001). We believe & 2011 Cancer Research UK