Outcome Of Febrile Neutropenia Research Articles

Malnutrition and neutropenia in children treated for Burkitt lymphoma in Malawi

Infection in neutropenic children is a major cause of morbidity and mortality in children treated for cancer. In developing countries, children with cancer are often malnourished at diagnosis. In Blantyre, Malawi, children with Burkitt lymphoma are treated with a local protocol with limited toxicity. The aim of this study was to evaluate the incidence and outcome of febrile neutropenia during this treatment and the association with malnutrition at diagnosis. We documented nutritional status, febrile and/or neutropenic episodes, antibiotic therapy and short term outcome of all children with Burkitt lymphoma treated according to the local protocol and admitted from January 2007 to March 2008. Fifty eight (69%) of 84 patients were acutely malnourished at diagnosis with an arm muscle area (AMA) below the 5(th) percentile. Malnutrition at diagnosis was associated with a significantly higher rate of profound neutropenia. This association remained significant (OR 12; 95% C.I. 1.5 - infinitely; P = 0.012) after control for clinical stage of disease, bone marrow involvement and HIV infection which are possible confounders. All patients with profound neutropenia, prolonged neutropenia and treatment related deaths were malnourished at diagnosis. Four (4.9%) of 81 patients died of treatment related causes; three of them due to a Gram negative septicaemia. Acute malnutrition at diagnosis is associated with significantly more treatment related profound neutropenia. The intensity of chemotherapeutic regimens has to be adapted to the level of available supportive care and patients' nutritional status and tolerance to avoid unacceptable morbidity and mortality. This local treatment protocol for Burkitt lymphoma has a treatment related mortality of 5% in patients in Malawi.

Use of Colony-Stimulating Factors for Chemotherapy-Associated Neutropenia: Review of Current Guidelines

Chemotherapy-associated neutropenia is often dose-limiting and may compromise treatment efficacy. Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage-colony-stimulating factor (GM-CSF) are increasingly used to prevent febrile neutropenia (FN) or to increase dose-density. This review discusses recent changes in treatment guidelines for chemotherapy-associated neutropenia. Primary prophylactic use of CSFs is now recommended as a treatment option at an overall risk of FN of 20%, not taking into account cost-effectiveness. To estimate the risk of FN, patient-, disease-, and treatment-related factors predicting an adverse outcome of FN have been determined. Dose-dense chemotherapy has become feasible with the use of CSFs. However, clinical benefit has been shown only for specific chemotherapy regimens in breast cancer, small cell lung cancer (SCLC), and non-Hodgkin's lymphoma (NHL), for the latter particularly for patients above 60 years of age. Strategies are being developed to tailor the use of CSFs to patients with a high risk of adverse outcome of FN.

Observational study of the prevalence of febrile neutropenia in patients who received filgrastim or pegfilgrastim associated with 3-4 week chemotherapy regimens in community oncology practices.

Colony-stimulating factors (CSFs) significantly decrease the risk of febrile neutropenia (FN), a common complication of myelosuppressive chemotherapy. Pegfilgrastim (6 mg), introduced in 2002, has a sustained duration of action, with a single dose comparable in efficacy to daily injections of filgrastim (5 g per kg per day) for 10 to 11 days; both agents should be initiated 24 hours after completing chemotherapy. To (1) describe the use of pegfilgrastim and filgrastim in oncology practices throughout the United States and (2) compare their effectiveness in actual practice as measured by the outcome of febrile neutropenia in patients who received chemotherapy regimens administered every 3 to 4 weeks for breast, lung, ovarian, colon cancer, or lymphoma and who received a CSF prior to developing FN. Data were retrospectively obtained from the medical records of a cohort of adult patients aged 18 years or older treated in 99 community oncology practices in the United States in 2001 and 2003. Eligible patients were treated with chemotherapy every 3 to 4 weeks for breast, lung, ovarian, colon cancer, or lymphoma and were users of filgrastim in 2001 (prior to the U.S. Food and Drug Administration approval of pegfilgrastim in January 2002) or users of either filgrastim or pegfilgrastim or both CSF agents in 2003. Pegfilgrastim was initiated, on average, 2.4 days (SD +/-3.2) after chemotherapy in the first cycle of use and 1.9 (+/-3.0) days in subsequent cycles of use. In contrast, filgrastim was started on average 7.7 (+/-6.5) days and 4.9 (4.6) days after chemotherapy in the first and subsequent cycles of use in 2001, increasing to 9.6 (+/-6.2) and 6.4 (+/-6.4) days in 2003. In the first cycle of CSF use, filgrastim was administered for an average of 5.2 (+/-3.5) days to 583 patients in 2001 and 3.7 (+/-2.8) days to 868 patients in 2003 (P <0.001). Among patients who received more than 1 cycle of filgrastim (n = 457 in 2001 and n = 489 in 2003; 78.4% and 56.3% of filgrastim users, respectively), the mean days of filgrastim administered in subsequent cycles was 6.0 (+/-3.5) in 2001 and 4.6 (+/-3.2) in 2003. Pegfilgrastim was administered as a single dose per chemotherapy course to 1,412 patients in 2003. Patients who received pegfilgrastim were more likely to have at least 1 myelosuppressive drug (74.8%) in the regimen compared with patients who received filgrastim in 2003 (70.0%, P = 0.013), but a greater proportion of filgrastim patients in 2003 (19.4%) had advanced-stage disease compared with pegfilgrastim patients (14.8%, P = 0.005). More patients who received filgrastim in 2003 (36.2%) had a cancer other than breast cancer or non-Hodgkin's lymphoma compared with those who received pegfilgrastim (29.5%, P = 0.001). A total of 94 of 1,451 patients (6.5%) who received filgrastim experienced FN compared with 67 of 1,412 patients (4.7%) for pegfilgrastim. The odds ratio of developing FN among patients who received filgrastim versus pegfilgrastim was 1.41 (95% confidence interval, 1.02-1.96; P = 0.040) after adjusting for patient and chemotherapy regimen characteristics. In this retrospective study of patients treated in 99 community oncology practices, patients who received filgrastim often initiated treatment later than recommended and received fewer days per cycle than demonstrated to be effective in randomized controlled trials. Pegfilgrastim was generally initiated earlier within the course of chemotherapy compared with filgrastim, and because of its sustained duration of action, only a single injection was required. In these patients treated with a heterogeneous group of chemotherapy regimens with a broad range of risk of FN, overall, an absolute 1.8% increase in the incidence of developing FN was observed in patients who received filgrastim compared with patients who received pegfilgrastim, (absolute rates of 6.5% and 4.7%, respectively).

Change of procalcitonin predicts clinical outcome of febrile episodes in patients with hematological malignancies

Procalcitonin (PCT) was widely investigated in febrile neutropenia as an indirect marker of infection. Many institutions also use PCT as a tool to monitor the course of a febrile episode because increases in PCT values during the febrile episode were associated with development of complications. However, to date, no study systematically evaluated the accuracy of decreasing PCT values in predicting favorable outcomes of a febrile episode. The aim of this study was to evaluate the changes in PCT values after resolution of fever with regard to their predictive value of stable defervescence. PCT was studied prospectively in 94 febrile episodes of 35 patients with hematological malignancies. Sixty-seven episodes were associated with an increased level of PCT at the beginning. In these episodes, stable resolution of fever was significantly correlated with a decrease in PCT values. The best cut-off level to predict freedom from recurrence of fever for at least 5 days was <70% of the maximum PCT value on the second afebrile day. Out of 44 patient episodes with a subsequent decrease to <70%, only two patients had recurrent fever within the next 5 days, revealing a negative predictive value of 95%, p<0.001. Our study supports the value of PCT as a reliable tool to predict clinical outcome in febrile neutropenia.