Kurt Leibundgut

Serum levels of mannose-binding lectin and the risk of fever in neutropenia pediatric cancer patients

Fever in neutropenia (FN) is a frequent complication in pediatric oncology. Deficiency of mannose‐binding lectin (MBL), an important component of innate immunity, is common due to genetic polymorphisms, but its impact on infections in oncologic patients is controversial. This study investigated whether MBL serum levels at cancer diagnosis are associated with the development of FN in pediatric cancer patients.

Risk prediction of fever in neutropenia in children with cancer: A step towards individually tailored supportive therapy?†‡

Fever in severe chemotherapy‐induced neutropenia (FN) is the most frequent manifestation of a potentially lethal complication of current intensive chemotherapy regimens. This study aimed at establishing models predicting the risk of FN, and of FN with bacteremia, in pediatric cancer patients.

First-day step-down to oral outpatient treatment versus continued standard treatment in children with cancer and low-risk fever in neutropenia. A randomized controlled trial within the multicenter SPOG 2003 FN study

The standard treatment of fever in chemotherapy‐induced neutropenia (FN) includes emergency hospitalization and empirical intravenous antimicrobial therapy. This study determined if first‐day step‐down to oral outpatient treatment is not inferior to continued standard regarding safety and efficacy in children with low‐risk FN.

An Investigation of the Steady-State Pharmacokinetics of Oral Valacyclovir in Immunocompromised Children

Valacyclovir was administered to 28 immunocompromised children (ages 5-12 years) to obtain preliminary pharmacokinetic and safety information. Patients were randomized to valacyclovir regimens of 250 mg (9.4-13.3 mg/kg) or 500 mg (13.9-27.0 mg/kg) twice daily or 500 mg (13.2-21.7 mg/kg) 3 times a day. Acyclovir pharmacokinetics were evaluated at steady state. Valacyclovir was rapidly absorbed and converted to acyclovir. Mean (+/-SD) acyclovir peak concentrations from 250 mg and 500 mg valacyclovir were 4.11+/-1.41 and 5.19+/-1.96 microg/mL, respectively. Corresponding single dose area-under-curve values were 12.14+/-6.60 and 14.49+/-4.69h microg/mL. By using historical data for intravenous acyclovir as reference, the overall estimate of acyclovir bioavailability from valacyclovir was 48%, 2- to 4-fold greater than for oral acyclovir. In general, adverse events were not attributable to valacyclovir and were consistent with disease-related expectations and concomitant therapies. Dosage options for using valacyclovir in children are discussed.

Evaluation of the Fresenius cell separator AS 104 for harvesting peripheral blood stem cells in pediatric patients

In a single institution trial we carried out 35 peripheral blood stem cell harvesting procedures in 12 children with advanced malignancies to evaluate the procedures safety and the collection efficiency of the Fresenius blood cell separator AS 104 in a pediatric population. Despite a significant mean decrease of 21% (+/-8%) in systolic blood pressure after starting the procedure, all children tolerated leukapheresis without any adverse reaction. After termination of leukapheresis there was a significant decrease of all determined hematological parameters, as compared with pre-harvest values. The mean mononuclear cell recovery was 64% (+/-26%), and in 25/35 (71%) harvesting procedures the minimum progenitor number required for safe autografting could be obtained by one single leukapheresis. We conclude that the Fresenius AS 104 blood cell separator provides a high cell yield and is a safe device for leukapheresis in pediatric patients.

Safety of ondansetron loading doses in children with cancer

IntroductionIn highly emetogenic chemotherapy, the recommended dose of the serotonin-receptor antagonist ondansetron (5xa0mg/m2 q8h) may be insufficient to prevent chemotherapy-induced nausea and vomiting. In adults, ondansetron-loading doses (OLD) of 32xa0mg are safe. We aimed to evaluate in children the safety of an OLD of 16xa0mg/m2 (top, 24xa0mg) i.v., followed by two doses of 5xa0mg/m2 q8h.Materials and methodsThis retrospective single-center study included all pediatric oncology patients having received ≥1 OLD between 2002 and 2005. Adverse events (AE) definitely, probably, or possibly related to OLD were studied, excluding AE not or unlikely related to the OLD. Associations between potential predictors and at least moderate AE were analyzed by mixed logistic regression.ResultsOf 167 patients treated with chemotherapy, 37 (22%) received 543 OLD. The most common AE were hypotension, fatigue, injection site reaction, headache, hot flashes/flushes, and dizziness. At least mild AE were described in 139 OLD (26%), at least moderate AE in 23 (4.2%), and severe AE in 5 (0.9%; exact 95% confidence interval [CI], 0.4–2.1). Life-threatening or lethal AE were not observed (0.0%; 0.0–0.6). At least moderate AE were significantly more frequent in female patients (odds ratio [OR] 3.5; 95% CI 1.4–8.8; pu2009=u20090.010), after erroneously given second OLD (17.0; 1.9–154; pu2009=u20090.012) and higher 24xa0h cumulative surface corrected dose (1.26 per mg/m2; 1.06–1.51; pu2009=u20090.009). OLD given to infants below 2xa0years were not associated with more frequent AE.ConclusionsOndansetron-loading doses of 16xa0mg/m2 (top, 24xa0mg) i.v. seem to be safe in infants, children, and adolescents.

Different fever definitions and the rate of fever and neutropenia diagnosed in children with cancer: A retrospective two‐center cohort study

The definition of fever, and thus fever and neutropenia (FN), varies between different pediatric oncology centers. Higher temperature limit should reduce FN rates, but may increase rates of FN with complications by delaying therapy. This study determined if different fever definitions are associated with different FN rates.

Serious medical complications in children with cancer and fever in chemotherapy‐induced neutropenia: Results of the prospective multicenter SPOG 2003 FN study

Fever and chemotherapy‐induced neutropenia (FN) is the most frequent potentially lethal complication of therapy in children with cancer. This study aimed to describe serious medical complications (SMC) in children with FN regarding incidence, clinical spectrum, and associated characteristics.

M-ficolin in children with cancer

OBJECTIVESnM-ficolin (ficolin-1) is a complement-activating pattern-recognition molecule structurally related to mannan-binding lectin. It is produced by monocytes and neutrophils, and is found in serum. Its biological role is largely unknown. We assessed M-ficolin concentration in serum from pediatric cancer patients. The aim of this study was to explore association of M-ficolin with clinical and hematological parameters, and to investigate whether the risk of chemotherapy-related infections was related to M-ficolin concentrations in serum.nnnMETHODSnM-ficolin was measured by time-resolved immunofluorometric assay in serum taken at cancer diagnosis and was correlated with peripheral blood counts and bone marrow examinations performed at the same time.nnnRESULTSnMedian M-ficolin concentration in 94 children with cancer was 1.6 μg/mL (interquartile range, 0.57-2.7; range, 0.055-25.8), and was not different from age-matched controls (median, 1.7 μg/mL; p=0.92). M-ficolin was strongly associated with absolute counts of neutrophils (Spearmans rho, 0.45; 95%-CI, 0.26-0.65; p<0.001), monocytes (0.34; 0.12-0.55; p<0.001), and thus phagocytes (0.42; 0.20-0.63; p<0.001) in peripheral blood. Similarly, M-ficolin correlated strongly with neutrophils (0.36; 0.14-0.59; p=0.002) and phagocytes (0.31; 0.08-0.54; p=0.009) in bone marrow. Low serum M-ficolin (≤0.5 μg/mL) was not associated with an increased incidence of fever in neutropenia during chemotherapy (multivariate Poisson rate ratio, 1.04; 95%-CI, 0.68-1.60; p=0.85).nnnCONCLUSIONSnThe concentration of M-ficolin in serum from children with cancer was strongly associated with neutrophil and monocyte counts in blood and bone marrow. These results suggest that M-ficolin concentrations in serum reflect the pool of phagocytes.

Single Institution Experience with Mobilization, Harvesting, and Reinfusion of Peripheral Blood Stem Cells in Children with a Solid Tumor or Leukemia

The aim of our single center pilot study was to evaluate the feasibility of peripheral blood stem cell autotransplantation (PBSCT) in a pediatric population. Only children with solid and hematological malignancies and poor prognosis who were without a HLA-identical bone marrow donor were included in this study. Mobilization of PBSC was done by treatment with myelosuppressive chemotherapy followed by recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Circulating progenitor cells were harvested by a total of 24 leukaphereses on an AS 104 cell separator in eight patients. Seven patients had undergone conditioning with high-dose chemotherapy with or without irradiation prior to PBSCT. All patients showed a rapid hematological recovery, although reconstitution of thrombopoiesis was incomplete in three children. We conclude that PBSCT is feasible in childhood and that it results in a rapid hematologic recovery.