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Childhood cancer survivors are at risk for treatment-related adverse health outcomes, known as late effects. Through matched and longitudinal cohorts, we assessed the impact of survivorship care on patient and parent knowledge of treatment history and associated health risks.Childhood cancer survivors were recruited from a single-institution survivorship clinic and matched with survivors receiving routine follow-up care (controls) on diagnosis, age, and time off therapy. One hundred seventy-four participants completed telephone interviews assessing knowledge of diagnosis, treatment history, and risk of late effects. Additionally, 48 new survivorship patients were followed longitudinally with serial interviews for 18 months.In the case-control study, survivorship participants were more likely than controls to correctly report their diagnosis (98% vs. 90%, P = 0.039) and indicate a previous discussion of risk of late effects (99% vs. 62%, P0.0001). Compared to controls, survivorship participants were 13% more sensitive reporting chemotherapeutics (95%CI 2.8-23.7%, P = 0.013) and 12% more sensitive reporting late effect risk (95%CI 7.3-16.6%, P0.0001). In the longitudinal cohort, participants were 7% more sensitive reporting chemotherapeutics (95%CI 5.4-10.8%, P 0.001) and 9% more sensitive reporting late effect risk (95%CI 5.6-23.8%, P0.001) at 3 months compared to baseline. In regression analysis, baseline knowledge correlated with subsequent interview performance, and time since survivorship visit correlated with decreased knowledge of late effects, but not diagnosis or treatment history.Survivorship care was associated with increased knowledge of diagnosis, treatment history, and risk of late effects in both cohorts. Knowledge of late effects decreases with time, suggesting the need for additional educational strategies.

Pediatric oncology patients are at increased risk for blood stream infections (BSI). Risk in the absence of severe neutropenia (absolute neutrophil count [ANC] ≥500/µl) is not well defined.In a retrospective cohort of febrile (temperature ≥38.0° for1 hr or ≥38.3°) pediatric oncology patients with ANC ≥500/µl, a diagnostic prediction model for BSI was constructed using logistic regression modeling and the following candidate predictors: age, ANC, absolute monocyte count, body temperature, inpatient/outpatient presentation, sex, central venous catheter type, hypotension, chills, cancer diagnosis, stem cell transplant, upper respiratory symptoms, and exposure to cytarabine, anti-thymocyte globulin, or anti-GD2 antibody. The model was internally validated with bootstrapping methods.Among 932 febrile episodes in 463 patients, we identified 91 cases of BSI. Independently significant predictors for BSI were higher body temperature (Odds ratio [OR] 2.36 P 0.001), tunneled external catheter (OR 13.79 P 0.001), peripherally inserted central catheter (OR 3.95 P = 0.005), elevated ANC (OR 1.19 P = 0.024), chills (OR 2.09 P = 0.031), and hypotension (OR 3.08 P = 0.004). Acute lymphoblastic leukemia diagnosis (OR 0.34 P = 0.026), increased age (OR 0.70 P = 0.049), and drug exposure (OR 0.08 P 0.001) were associated with decreased risk for BSI. The risk prediction model had a C-index of 0.898; after bootstrapping adjustment for optimism, corrected C-index 0.885.We developed a diagnostic prediction model for BSI in febrile pediatric oncology patients without severe neutropenia. External validation is warranted before use in clinical practice. Pediatr Blood Cancer 2015;62:262-268. © 2014 Wiley Periodicals, Inc.

Corticosteroids increase risk for decreased bone mineral density, which can be worsened by vitamin D insufficiency (VDI) or deficiency (VDD).In the Vanderbilt cancer survivorship clinic, we obtained screening total 25-hydroxy vitamin D levels (VDL) in 171 cancer survivors23 years old who were treated with prolonged corticosteroids for their cancer, and compared this group to a control group of 97 healthy pediatric patients.VDD was diagnosed in 15.8% and VDI in 34.5% of cancer survivors and VDD/VDI combined was associated with body mass index (BMI)85th percentile (Odds ratio [OR] = 5.4; P 0.001), older age (OR = 2.2; P = 0.012), non-Caucasian or Hispanic race (OR = 4.5; P = 0.008) and summer versus winter season (OR = 0.12; P 0.001). In multivariable analysis, VDI/VDD prevalence did not differ from the control group (VDI/VDD (43.3%)). In the combined survivor/control group multivariable analysis, cancer diagnosis did not increase VDI/VDD risk, but significant associations persisted with elevated BMI (P 0.001), age (P = 0.004), non-Caucasian or Hispanic race (P 0.001), and seasonality (P 0.001).VDD/VDI is equally common in pediatric cancer survivors treated with corticosteroids and healthy children. The impact of VDD/VDI in cancer survivors may be greater due to risk for impaired bone health superimposed on that conferred from corticosteroid exposure. Thus, screening VDLs should be obtained in pediatric cancer survivors treated with corticosteroids, particularly in those with elevated BMI, older age, or non-Caucasian race. Prospective studies evaluating the impact of interventions to minimize VDD/VDI on long-term bone health in survivors are required.

BACKGROUND: Dapsone, used for Pneumocystis jiroveci (PCP) prophylaxis, is associated with increased risk of methemoglobinemia. Absence of cytochrome b5 reductase enzyme activity causes congenital methemoglobinemia, but its role in dapsone-associated methemoglobinemia is unknown. The authors sought to elucidate drug-related risk factors for dapsone-associated methemoglobinemia in pediatric oncology patients, including contribution of cytochrome b5 reductase enzyme activity. METHODS: Among 167 pediatric patients treated for hematologic malignancies or aplastic anemia who received dapsone for PCP prophylaxis, demographic and dapsone treatment data were retrospectively collected. Drug-related risk factors were evaluated by Cox proportional hazards, and in a cross-sectional subgroup of 40 patients, cytochrome b5 reductase enzyme activity was assessed. RESULTS: Methemoglobinemia (median methemoglobin level = 9.0% [3.5-22.4]) was documented in 32 (19.8%) patients. There was a 73% risk reduction in methemoglobinemia with dosing ≥20% below the target dose of 2 mg/kg/d (hazard ratio [HR], 0.27; 95% confidence interval [CI], 0.09-0.78; P = .016), whereas methemoglobinemia risk was increased with dosing ≥20% above the target dose (HR, 6.25; 95% CI, 2.45-15.93; P < .001). Sex, body mass index, and age were not associated with increased risk. Cytochrome b5 reductase enzyme activity did not differ by methemoglobinemia status (median 8.6 IU/g hemoglobin [Hb]; [5.5-12.1] vs 9.1 IU/g Hb; [6.7-12.7]). No patient developed PCP on dapsone. CONCLUSIONS: Methemoglobinemia occurred in almost 20% of pediatric oncology patients receiving dapsone for PCP prophylaxis. Higher dapsone dosing is associated with increased risk. A cross-sectionally acquired cytochrome b5 reductase enzyme activity level was not associated with methemoglobinemia risk. Studies are needed to define biologic correlates of methemoglobinemia and evaluate lower dapsone doses for PCP prophylaxis. Cancer 2011. © 2011 American Cancer Society.

Ehrlichiosis, a tickborne illness transmitted by tick vectors Amblyomma americanum and Ixodes scapularis, can be acquired in endemic areas. Clinical manifestations range from asymptomatic to fulminant in nature. We report three cases of ehrlichiosis in pediatric oncology patients, one of whom was a stem cell transplant recipient. Early symptoms included fever, malaise, and vague gastrointestinal symptoms. Laboratory abnormalities were initially attributed to chemotherapy toxicity. Illness was severe in all three patients and one patient died even after initiation of doxycycline. These cases emphasize the need for a high index of suspicion for tickborne illness in oncology patients, and the importance of a low threshold for starting empiric treatment before confirming the diagnosis. Pediatr Blood Cancer 2010;54:776–778. © 2010 Wiley-Liss, Inc.

e19611 Background: Pediatric acute lymphoblastic leukemia (ALL) survivors are at increased risk for the metabolic syndrome. We examined the trajectory of development over the first year of maintena...

4114 The metabolic syndrome, which includes obesity, hypertension, dyslipidemia, and insulin resistance, has been reported to occur in excess among long term survivors of pediatric acute lymphoblastic leukemia (ALL). Among known risk factors are exposure to corticosteroids and cranial radiotherapy. However, at what point along the trajectory of therapy that the metabolic abnormalities develop is unclear. Twenty-two consecutively enrolled patients with pre-B or T cell ALL treated on or according to Children's Oncology Group protocols at Vanderbilt Children's Hospital were evaluated for components of the metabolic syndrome at the start of maintenance chemotherapy. The overall prevalence of metabolic syndrome traits in this cohort was high, with 19 (86%) subjects exhibiting at least 1 component of the metabolic syndrome. Of those, 4 (21%) met full criteria for metabolic syndrome (demonstrating at least 3/5 components) ([Table 1][1]). Dyslipidemia was common with 11/22 (50%) having a fasting HDL ≤ 40mg/dl [median= 35mg/dl; 1st/3rd quartiles (29, 38)] and 8/22 (36%) having fasting triglycerides >110 mg/dl [median=165mg/dl; (129, 340)]. Patients with ALL NCI high risk classification had higher fasting triglycerides (p