Wim J. E. Tissing

Currently, very few guidelines for supportive care for children with cancer exist. In the Netherlands, nationwide guidelines are over 10 years old and mostly based on expert opinion. Consequently, there is growing support and need for clinical practice guidelines (CPGs), which ought to be developed with a well-defined methodology and include a systematic search of literature, evidence summaries, and a transparent description of the decision process for the final recommendations. Development of CPGs is time consuming; therefore, it is important to prioritize topics for which there is the greatest clinical demand. This study aims to prioritize childhood cancer supportive care topics for development of CPGs. A Delphi survey consisting of two rounds was conducted to prioritize relevant childhood cancer supportive care topics for the development of CPGs. A group of experts comprising 15 pediatric oncologists, 15 pediatric oncology nurses, and 15 general pediatricians involved in care for childhood cancer patients were invited to participate. All relevant supportive care topics in childhood cancer were rated. In both rounds, 36 panellists (82 %) responded. Agreement between panellists was very good, with an intraclass correlation coefficient of 0.918 (95 % confidence interval (CI) = 0.849–0.966, p < 0.001) in round 2. The ten topics with the highest score in the final round were infection, sepsis, febrile neutropenia, pain, nausea/vomiting, restrictions in daily life and activities, palliative care, procedural sedation, terminal care, and oral mucositis. We successfully used a Delphi survey to prioritize childhood cancer supportive care topics for the development of CPGs. This is a first step towards uniform and evidence-based Dutch guidelines in supportive care in childhood cancer. Even though performed nationally, we believe that this study can also be regarded as an example starting point for international development of CPGs in the field of supportive care in cancer or any other field for that matter.

In childhood cancer patients, malnutrition has been proposed to increase infection rates and reduce survival. We investigated whether malnutrition at diagnosis and during treatment and weight loss during treatment are prognostic factors for infection rates and survival, within a heterogeneous childhood cancer population. From two previous studies, all children ≤18 years of age diagnosed with cancer between October 2004 and October 2011 were included in this study. Data regarding BMI, infections, and survival were retrieved. Patients with a BMI z-score lower than −2.0 were classified as malnourished. Weight loss more than 5 % was considered relevant. Two hundred sixty-nine childhood cancer patients were included in this study. At diagnosis, 5.2 % of all patients were malnourished. These patients showed worse survival than those who were well nourished (hazard ratio (HR) = 3.63, 95 % confidence interval (CI) = 1.52–8.70, p = 0.004). Malnourishment at 3 months after diagnosis (3.3 % of all patients) also showed worse survival (HR = 6.34, 95 % CI = 2.42–16.65, p < 0.001). Weight loss of more than 5 % in the first 3 months after diagnosis was related to increased occurrence of febrile neutropenic episodes with bacteremia in the first year after diagnosis (odds ratio (OR) = 3.05, 95 % CI = 1.27–7.30, p = 0.012). We found that malnourishment in the initial phase of therapy is associated with worse survival in childhood cancer patients. In addition, we found for the first time that weight loss during treatment is associated with increased presence of febrile neutropenic episodes with bacteremia. This underlines the importance of optimal feeding designs in childhood cancer patients.

Purpose In this study, we evaluated C-reactive protein (CRP), interleukin (IL)-8, procalcitonin (PCT), and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as predictors for bacterial infection in febrile neutropenia, plus their usefulness in febrile neutropenia during chemotherapy-induced gastrointestinal mucositis. Methods Plasma was obtained from pediatric oncology patients at presentation with febrile neutropenia (n = 43) and 24–48 h later (n = 17). The patients were classified as having or not having a bacterial infection. Plasma was also obtained of patients in the absence and in the presence of mucositis (n = 26). Results At presentation with febrile neutropenia, median IL-8 and PCT levels were significantly increased in patients with a bacterial infection, in contrast to CRP and sTREM-1. IL-8 was the most sensitive marker for the early detection of bacterial infection, in combination with clinical parameters or PCT the sensitivity reached 100%. After 24–48 h, only PCT was significantly elevated during bacterial infection. IL-8 levels were significantly increased during mucositis. Mucositis did not cause considerable changes in PCT levels. Conclusions IL-8 is the most useful marker for the early detection of bacterial infections, compared with CRP, PCT, and sTREM-1. IL-8 in combination with clinical parameters or PCT might be even more useful. Gastrointestinal mucositis alone does not affect PCT levels, in contrast to IL-8 levels, and therefore, PCT might be more useful for the detection of bacterial infections during mucositis than IL-8.

Background: The currently used National Cancer Institute (NCI) adverse events criteria for mucosal barrier injury (MBI) are insufficient for use in children. We searched for objective, easily measurable indicators for MBI in children with cancer.Purpose: In children with acute myeloid leukemia, various MBI‐related clinical and laboratory tests were investigated, reflecting clinical severity (NCI symptomatic adverse events criteria (gold standard), daily gut score (DGS)), inflammation (plasma and fecal interleukin‐8 (IL‐8), fecal calprotectin), enterocytic loss (plasma citrulline, ratio fecal human DNA/total DNA) and intestinal permeability (sugar absorption tests).Results: Intestinal MBI as detected by the NCI adverse events criteria was found in 55% of chemotherapy cycles, correlating well with the continuous DGS (n = 55, rho = 0.581; P < 0.001). Intestinal cell loss as measured by the ratio fecal human DNA/total DNA and plasma citrulline correlated well with both NCI criteria (n = 61, rho = 0.357, P = 0.005 resp. n = 58, rho = −0.482; P < 0.001) and DGS (n = 54, rho = 0.352, P = 0.009 resp. n = 55, rho = −0.625; P < 0.001). Plasma IL‐8 correlated strongly to plasma citrulline (n = 46, rho = −0.627; P < 0.001).Conclusions: MBI was reflected by parameters indicating inflammation (IL‐8) and cell loss (plasma citrulline, ratio fecal human DNA/total DNA). We conclude that plasma citrulline might be a good parameter for MBI. Further studies are needed to show whether plasma citrulline can be used as a marker for MBI in future research. Pediatr Blood Cancer 2009; 53:1188–1194.

Background.Normally, humans are protected against infections by their anaerobic intestinal microorganisms providing colonization resistance. In immun