Subject(s)
Antineoplastic Agents/adverse effects , Fever/chemically induced , Models, Statistical , Neoplasms/drug therapy , Neutropenia/chemically induced , Antineoplastic Agents/administration & dosage , Child , Child, Preschool , Dose-Response Relationship, Drug , Female , Fever/epidemiology , Humans , Male , Neoplasms/pathology , Neutropenia/epidemiology , Predictive Value of Tests , Prognosis , Risk AssessmentABSTRACT
We report an increased incidence of infectious deaths during maintenance treatment of the ninth protocol for acute lymphoblastic leukaemia of the Dutch Childhood Oncology Group (DCOG-ALL-9). The main difference in maintenance treatment between DCOG-ALL-9 and the DCOG-ALL-7 and DCOG-ALL-8 protocols is the interruption of methotrexate and 6-mercaptopurine by vincristine (2mg/m(2) weekly) and dexamethasone (6mg/m(2) daily) for 14 days every 7 weeks in the DCOG-ALL-9 protocol. The 1107 children treated with the DCOG-ALL-7, DCOG-ALL-8 or DCOG-ALL-9 protocol were included and screened for infectious death during maintenance treatment (July 1988-July 2002). Seven of the 510 children died of severe infections during the maintenance phase of DCOG-ALL-9, compared to none of the 597 patients during the DCOG-ALL-7 and DCOG-ALL-8 protocols (1.37% versus 0.0%; p=0.013). Results from the current study suggest that repeated, prolonged exposure to dexamethasone results in an increase of lethal infections from 0% to 1.37%. In the dosing-schedule used, the advantage of dexamethasone may not outweigh the higher risk of infectious death.
Subject(s)
Antineoplastic Agents, Hormonal/adverse effects , Dexamethasone/adverse effects , Opportunistic Infections/chemically induced , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child , Child, Preschool , Female , Humans , Male , Opportunistic Infections/mortality , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Retrospective Studies , Risk FactorsABSTRACT
PURPOSE: To investigate the feasibility of withholding antibiotics and early discharge for patients with chemotherapy-induced neutropenia and fever at low risk of bacterial infection by a new risk assessment model. PATIENTS AND METHODS: Outpatients with febrile neutropenia were allocated to one of three groups by a risk assessment model combining objective clinical parameters and plasma interleukin 8 level. Patients with signs of a bacterial infection and/or abnormal vital signs indicating sepsis were considered high risk. Based on their interleukin-8 level, remaining patients were allocated to low or medium risk for bacterial infection. Medium-risk and high-risk patients received standard antibiotic therapy, whereas low-risk patients did not receive antibiotics and were discharged from hospital after 12 hours of a febrile observation. End points were the feasibility of the treatment protocol. RESULTS: Of 196 assessable episodes, 76 (39%) were classified as high risk, 84 (43%) as medium risk, and 36 (18%) as low risk. There were no treatment failures in the low-risk group (95% CI, 0% to 10%). Therefore, sensitivity of our risk assessment model was 100% (95% CI, 90% to 100%), the specificity, positive, and negative predictive values were 21%, 13%, and 100%, respectively. Median duration of hospitalization was 3 days in the low-risk group versus 7 days in the medium- and high-risk groups (P < .0001). The incremental costs of the experimental treatment protocol amounted to a saving of 471 (US $572) for every potentially low-risk patient. CONCLUSION: This risk assessment model appears to identify febrile neutropenic patients at low risk for bacterial infection. Antibiotics can be withheld in well-defined neutropenic patients with fever.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Antineoplastic Agents/adverse effects , Fever/prevention & control , Neoplasms/drug therapy , Neutropenia/prevention & control , Adolescent , Adult , Aged , Bacterial Infections/drug therapy , Bacterial Infections/etiology , Child , Child, Preschool , Feasibility Studies , Female , Fever/etiology , Humans , Infant , Infant, Newborn , Interleukin-8 , Male , Middle Aged , Neutropenia/chemically induced , Patient Discharge , Predictive Value of Tests , Prospective Studies , Risk AssessmentABSTRACT
OBJECTIVE: Cancer patients with febrile neutropenia after chemotherapy have a variable risk of bacterial infection. Especially Gram-negative bacteremia is associated with high mortality and/or morbidity. Early diagnosis of patients with Gram-negative bacteremia at the onset of febrile neutropenia is potentially useful in tailoring therapy. DESIGN AND SETTING: Prospective study at the Department of Pediatric Oncology and Internal Medicine of a university hospital. PATIENTS: Were analyzed 66 febrile neutropenic episodes in 57 adults and children. Patients were divided into four groups: those with Gram-negative bacteremia, Gram-positive bacteremia, clinical sepsis, or fever of unknown origin. MEASUREMENTS AND RESULTS: Plasma lipopolysaccharide-binding protein (LBP) and C-reactive protein (CRP) concentrations were determined. LBP at the onset of febrile neutropenia was significantly higher in patients with Gram-negative bacteremia than those with fever of unknown origin and those with Gram-positive bacteremia. Using a cutoff value for LBP proved to have much greater sensitivity, specificity, and positive and negative predictive value for Gram-negative bacteremia than the best cutoff value for CRP. CONCLUSIONS: An initial high LBP level might predict Gram-negative bacteremia in cancer patients with febrile neutropenia. These results may have potential clinical impact by allowing therapy to be initiated for these patients at a very early stage.
