Febrile neutropaenia in apparently stable outpatients A Carmona-Bayonas et al Variables tested as potential risk factors in febrile neutropaenia Table 2 outcome Variables Baseline characteristics and medical history Age, years Sex Surgery in the previous month ECOG performance status Antibiotics in the previous month Constitutional syndrome COPD Chronic heart failure Diabetes mellitus Lung cancer Lymphoma Breast cancer TNM stage Prophylactic GCSF Adjuvant chemotherapy Laboratory results Albumin, g dl 1 Total proteins, g dl 1 LDH, mU ml 1 Monocytes at the onset, mm 3 Platelets at the onset, mm 3 Haemoglobin at the onset, g dl 1 Neutrophils at the onset, mm 3 Fibrinogen, mg dl 1 Uraemia, mg dl 1 Stress hyperglycaemiaa Characteristics of the febrile neutropaenia episode Productive cough Urinary infection Fever of unknown origin Abnormal X-ray without pneumonia at the onset Heart rate X91 Respiratory rate X21 MASCC score Burden of disease at the onset Dehydration Chills Temperature at the onset, 1C Stomatitis NCI grade X2 Table 1 The MASCC index score Category Burden of illness: no or mild symptoms No hypotension No chronic obstructive pulmonary disease Solid tumour or no previous invasive fungal infection Outpatient status Burden of disease: moderate symptoms No dehydration Aged o60 years Weight 5 5 4 4 3 3 3 2 Abbreviation: MASCC ¼ Multinational Association of Supportive Care in Cancer. The maximum theoretical score is 26. A MASCC score X21 identifies low-risk patients with a positive predictive value of 91%, specificity of 68% and sensitivity of 71% (Klastersky et al, 2000). neutropaenia p500 mm 3 (or a count of p1000 cells mm 3 with a predicted decrease to p500 cells mm 3), chemotherapy and a solid tumour were reviewed. Patients treated with high-dose chemo- therapy (HDC), including induction and intensification for acute leukaemia, BMT, the Magrath regimen and other induction treatments for Burkitt lymphoma, were excluded. The episode was considered valid if the management complied with current IDSA guidelines for FN (Hughes et al, 2002). Oral or ambulatory therapy was not offered. We additionally excluded the episodes in which X10% of the variables tested were missing. In case of multiple episodes for one patient, only the first one was evaluated. The study protocol was approved by the hospital investigational review board, and informed consent was obtained from patients. Study design Initial risk stratification We used objective criteria, such as the blood pressure, X-rays and blood tests, to classify the episodes into two categories: apparently stable patients (ASPs) and clearly unstable patients (CUPs). The CUP subgroup included those patients with any of these features at presentation: acute organ dysfunction, septic shock, hypotension, extensive infections (pneumonia, cellulitis 45 cm, typhlitis, meningitis and pyelone- phritis) or any other acute comorbidity indicating hospital admission by itself. Patients without the attributes that charac- terised CUPs were considered ASPs. The medical records of the whole ASP group were reviewed to analyse the prevalence of complications that were not present at the diagnosis of FN, which comprised the triage and a basic workup (around 3 h). Potential risk factors in the ASP group We designed a retrospective case – control study. Both cases and controls were obtained from the same base (ASP group). A case was defined as a patient with an unexpected serious complication after admission. These events were defined according to the MASCC criterion (Klastersky et al, 2000). All cases were included in the analysis. In patients with multiple complications, we considered the most severe one to define the case. A control was defined as a randomly selected patient who was not a case. The whole ASP subgroup was analysed to calculate the prevalence of complications and to provide a completely randomised selection of controls. For the multivariate study, we planned a ratio of 1 : 2 for cases and controls, plus additional 25% controls to compensate missing values. No matching techniques were used. Selection of prognostic variables was performed after reviewing the literature and considering their availability in the Emergency Room setting. We also omitted the variables that were not accessible at the onset. Burden of disease was evaluated as in Klastersky et al (2000). Constitutional syndrome was defined as the presence of asthenia, anorexia and loss of X10% of body weight in the previous 3 months. As outlined in Table 2, most of the variables were dichotomic. For continuous variables, cutoffs were & 2011 Cancer Research UK Abbreviations: COPD ¼ chronic obstructive pulmonary disease; ECOG ¼ Eastern Cooperative Oncology Group; GCSF ¼ granulocyte-colony stimulating factor; LDH ¼ lactate dehydrogenase; MASCC ¼ Multinational Association of Supportive Care in Cancer; NCI ¼ National Cancer Institute; TNM ¼ tumour-node-metastasis. aStress hyperglycaemia: X121 mg dl 1 (X250 mg m 2 in diabetic patients). defined according to previous reports (Groeger et al, 1998) or, when unavailable, to clinically relevant or NCI toxicity scale-based cutoffs. Statistical considerations For the univariate analysis, each potential risk factor was assessed using w2-test or, when appropriate, Fisher exact test. Those variables with a P-value o0.20 were eligible for the multivariate analysis. The variables with X10% of missing values (chills, heart rate, respiratory rate and fibrinogen) were excluded. Clinical redundancy and potential overlapping was also a reason for exclusion. The covariates finally included in the stepwise logistic regression model were: age, sex, ECOG, constitutional syndrome, COPD, albumin, monocytes, platelets, uraemia, stress hypergly- caemia, productive cough, abnormal X-rays without pneumonia, stomatitis, chronic heart failure, burden of disease, lung cancer and breast cancer. Statistical analyses were carried out with the British Journal of Cancer (2011) 105(5), 612 – 617 Categories X65, o65 Male, female Yes, no X2, o2 Yes, no Yes, no Yes, no Yes, no Yes, no Yes, no Yes, no Yes, no IV, I – III Yes, no Yes, no o3, X3 o6.4, X6.4 X475 , o475 o200, X200 o1 00 000, X1 00 000 p9, 49 p100, 4100 X450 , o450 X30 mg, o30 Yes, no Yes, no Yes, no Yes, no Yes, no Yes, no Yes, no o21, X21 Moderate, low Yes, no Yes, no X39, o39 Yes, no 613 s e i d u t S l a c i n i l C