A Case of Anti-NMDA Receptor Encephalitis During Dinutuximab Therapy for Neuroblastoma.

Dinutuximab is a monoclonal antibody administered to patients with high-risk neuroblastoma, usually after an autologous stem cell transplant. Dinutuximab is associated with immune mediated and neurologic toxicities, but fatal adverse events are rare. A case is presented of high-risk neuroblastoma with development of encephalopathy shortly after the first course of dinutuximab. The patient had extensive evaluation for etiology of the symptoms and received aggressive interventions, but ultimately expired. Postmortem diagnosis of anti-N-methyl D-aspartate receptor encephalitis, an autoimmune phenomenon often triggered by infection or malignancy, was made. The potential association of autoimmune encephalitis with dinutuximab and with previous autologous transplant is discussed.

Lineage Assignment in Acute Leukemia: A Challenging Case in a Pediatric Patient.

We report a case of a 2-year-old girl who was diagnosed with natural killer cell acute lymphoblastic leukemia and treated with an acute lymphoblastic leukemia chemotherapy regimen. Two months posttherapy, the disease relapsed with a myeloid immunophenotype. Complete response was then achieved with acute myeloid leukemia therapy followed by unrelated donor umbilical cord allogenic stem cell transplant. Retrospectively, reanalysis of the diagnostic specimen showed minimal myeloperoxidase expression that was called negative by conventional single parameter linear gating but better appreciated on histogram overlays. This case illustrates that even low levels of myeloperoxidase expression should be considered significant in lineage assignment in acute leukemia.

Blood Stream Infections and Antibiotic Utilization in Pediatric Leukemia Patients With Febrile Neutropenia.

BACKGROUND: Frequent surveillance of bacterial pathogens responsible for microbiologically defined-blood stream infections (MD-BSI), and their respective antibiotic susceptibilities is central to tailoring empiric antibiotic therapy in febrile neutropenia (FN) episodes in pediatric patients with leukemia. The safety of deescalating antibiotic therapy in pediatric patients with leukemia and neutropenia is incompletely understood. METHODS: A retrospective chart review of 194 FN episodes occurred between the years of 2013 and 2016 in 67 patients with leukemia. Clinical and microbiologic data were recorded. RESULTS: MD-BSI occurred in 36 of 194 (18%) of FN episodes. Deescalation of empiric antibiotic therapy based on antibiotic susceptibilities was possible in 25 of 36 (69.4%) episodes. In those 25 episodes, where there was an opportunity to deescalate the antibiotic spectrum, it was clinically appropriate to do so in 19. Deescalation occurred in 9 (47.4%) of these episodes without complication. The remaining 10 patients received a median of 20 additional days of broad-spectrum antibiotic therapy (range, 12 to 30 d). CONCLUSIONS: In our small cohort of patients, deescalation of antibiotic therapy based on antimicrobial susceptibilities did not result in complication. Larger prospective studies are needed to address the safety of deescalating antibiotic therapy in this population.

Management and outcomes of patients with renal medullary carcinoma: a multicentre collaborative study.

OBJECTIVE: To describe the management strategies and outcomes of patients with renal medullary carcinoma (RMC) and characterise predictors of overall survival (OS). PATIENTS AND METHODS: RMC is a rare and aggressive malignancy that afflicts young patients with sickle cell trait; there are limited data on management to date. This is a study of patients with RMC who were treated in 2000-2015 at eight academic institutions in North America and France. The Kaplan-Meier method was used to estimate OS, measured from initial RMC diagnosis to date of death. Cox regression analysis was used to determine predictors of OS. RESULTS: In all, 52 patients (37 males) were identified. The median (range) age at diagnosis was 28 (9-48) years and 49 patients (94%) had stage III/IV. The median OS for all patients was 13.0 months and 38 patients (75%) had nephrectomy. Patients who underwent nephrectomy had superior OS compared to patients who were treated with systemic therapy only (median OS 16.4 vs 7.0 months, P < 0.001). In all, 45 patients received chemotherapy and 13 (29%) had an objective response; 28 patients received targeted therapies, with 8-week median therapy duration and no objective responses. Only seven patients (13%) survived for >24 months. CONCLUSIONS: RMC carries a poor prognosis. Chemotherapy provides palliation and remains the mainstay of therapy, but <20% of patients survive for >24 months, underscoring the need to develop more effective therapy for this rare tumour. In this study, nephrectomy was associated with improved OS.

Blood Cultures for Persistent Fever in Neutropenic Pediatric Patients Are of Low Diagnostic Yield.

The incidence of bacteremia at the onset of pediatric febrile neutropenia (FN) at 2 academically linked institutions was 9.84%, and subsequent blood cultures performed for children with persistent FN yielded an incidence of 4.21%. Until the risk factors for new-onset bacteremia in patients being treated for FN can be identified and diagnostic methods can be improved, compliance with national guidelines is recommended.

Vincristine, irinotecan, and temozolomide for treatment of relapsed alveolar rhabdomyosarcoma.

Event-free survival for recurrent alveolar rhabdomyosarcoma (ARMS) is poor, and a consensus approach to treatment in the relapse setting has not been established. Recent studies suggest that a combination regimen of vincristine, irinotecan, and temozolomide (VITA) is active against recurrent sarcomas. We present our single-institution experience with this regimen for relapsed ARMS in heavily pretreated patients, including those with prior exposure to a combination regimen of vincristine and irinotecan. We observed a complete radiographic response in 1 of 4 patients who received VITA as a fifth attempted salvage regimen. Radiographic remission for the responsive patient was sustained for 27 weeks before disease recurrence. All therapies were administered in the outpatient setting and no grade III or grade IV toxicities were observed. These findings suggest that for patients with refractory ARMS, VITA in combination should be among the treatment options considered. They also reinforce the need for biological correlates to prospectively identify patients who may benefit from this treatment.

Impact of pelvic CT on staging, surveillance, and survival of pediatric patients with Wilms tumor and hepatoblastoma.

OBJECTIVE: Abdominopelvic CT is often performed in children with Wilms tumor or hepatoblastoma. However, the reported incidence of recurrent disease involving the pelvis is low. This study explores the impact of abdominopelvic CT on children with Wilms tumor or hepatoblastoma. MATERIALS AND METHODS: A text word database search of our radiology information system for the terms "Wilms" and "hepatoblastoma" was performed for the time interval between 1999 and 2009. The study inclusion criterion was performance of abdominopelvic CT. Tumor stage and metastases at presentation, follow-up, and impact on patient care were extracted from the medical records. RESULTS: There were 224 diagnostic and surveillance abdominopelvic CT studies (mean per patient, 6.8; range, 2-20). Among Wilms tumor (n = 17) and hepatoblastoma (n = 16) patients, at presentation 11 (33%) had pelvic extension of the tumor and three (9%) had pulmonary metastases. On follow-up, three (9%) additional patients developed metastatic disease or local recurrence; however, no patient was found to have pelvic metastases or recurrence. One patient with metastatic disease at presentation died. CONCLUSION: In our study population, abdominopelvic CT did not detect pelvic metastases to affect subsequent treatment. Given the low rate of pelvic involvement at relapse in children with Wilms tumor and hepatoblastoma, frequent abdominopelvic CT may not be necessary. Replacing these examinations with abdomen-only CT should be considered to decrease radiation burden to this population.

Impact of abdominopelvic CT on Ewing sarcoma management.

RATIONALE AND OBJECTIVES: Abdominopelvic computed tomography (APCT) is often performed in patients with skeletal Ewing sarcoma family of tumors during initial staging and for subsequent clinical indications, such as metastasis surveillance; however, its clinical impact is unknown. The purpose of this study was to evaluate whether these computed tomographic examinations alter oncologic management and therefore patient outcomes. MATERIALS AND METHODS: One hundred eight consecutive patients with skeletal Ewing sarcoma family of tumors seen from 1985 to 2008 were retrospectively reviewed to identify imaging workup, pathology, primary site, evidence of metastatic disease, and patient outcomes. Data were analyzed using Wilcoxon's rank sum tests. RESULTS: Sixty-five of the 108 patients (60%) underwent 342 abdominopelvic computed tomographic examinations during a mean follow-up period of 8.9 years. During this time period, only one of the 65 patients (1.5%) who underwent APCT was discovered to have abdominal metastatic disease. There was no significant difference in the incidence of metastatic disease to the skeleton or chest between the groups without and with APCT (P = .10). There were 26 pelvic and lumbosacral primaries (24%) and 82 limb primaries (76%). Subgroup analysis performed on the 82 patients with limb primaries without (n = 36) and with (n = 46) APCT showed no significant differences in metastatic incidence to the skeleton or chest (P = .14). CONCLUSIONS: This study indicates that APCT, associated with increased radiation exposure and health expenditure, has a limited role in initial staging and follow-up in patients with skeletal Ewing sarcoma, particularly in patients with limb primaries.

Body mass index predicts insulin resistance in survivors of pediatric acute lymphoblastic leukemia.

BACKGROUND: Pediatric acute lymphoblastic leukemia (ALL) therapies have been associated with many late effects, including obesity, hyperglycemia, and insulin resistance. Few data are available linking these abnormalities to specific risk factors present during ALL treatment. METHODS: Retrospective cohort study with prospective follow-up. Subjects had been diagnosed with ALL at ages 1-18 years and had been off chemotherapy for >9 months. Oral glucose tolerance testing (OGTT) was performed and these results compared to demographic, treatment, and anthropomorphic data from medical records. RESULTS: Twenty-seven subjects (11 female) were evaluated. Mean (+/-SD) diagnosis age 5.7 +/- 3.5 years, mean study age 11.3 +/- 3.7 years, mean time off therapy 2.8 +/- 1.5 years. Six subjects had transient hyperglycemia during ALL treatment. At study time, one subject had prediabetes; eight (29.6%) had insulin resistance. Insulin resistance was not predicted by glucose levels during treatment, cumulative steroid or asparaginase dose, or type of steroid received. Body mass index (BMI) for age correlated significantly with several measures of insulin resistance, including fasting insulin, HOMA index, Matsuda index and insulin AUC (P = 0.001-0.009). Waist/hip ratio and BMI at ALL diagnosis also correlated with insulin resistance, but these factors' effects could not be separated from BMI at study time. CONCLUSIONS: Variations in ALL therapy and presence of transient hyperglycemia do not appear to increase risk of glucose intolerance or insulin resistance in the first few years after completion of therapy. Elevated BMI strongly predicted insulin resistance in this study, as it does in the general population.

Prevalence of transient hyperglycemia during induction chemotherapy for pediatric acute lymphoblastic leukemia.

BACKGROUND: Transient hyperglycemia (TH) is a recognized side effect of the corticosteroids and asparaginase given during induction chemotherapy for pediatric acute lymphoblastic leukemia (ALL). Information is needed about how TH has been impacted by changes in ALL therapy. This study examined the prevalence of TH in a cohort of pediatric ALL patients and the impact on TH of type of steroid or asparaginase used and of risk factors such as age, gender, and overweight. METHODS: Retrospective record review of patients aged 2-18 years diagnosed with ALL in 1999-2006. TH was defined as >or=2 random glucose values >or=200 mg/dl. Overall prevalence of TH was calculated. Risk factors were evaluated using Chi-square analysis and logistic regression. RESULTS: One hundred sixty-two subjects (70 female) were reviewed, 33 (20.4%) of whom had TH. 42.2% of subjects over age 10 years had TH, compared to 12.0% of younger children (P < 0.001). No gender difference was found. Overweight (BMI >or= 95th percentile) and at risk for overweight (BMI >or= 85th percentile) were significant risk factors for TH (P = 0.007 and P = 0.003, respectively). Native L-asparaginase was associated with increased TH compared to PEG-asparaginase (P = 0.047). There was a non-significant trend toward more TH in patients who received prednisone, but this disappeared in multivariate analysis. CONCLUSIONS: The prevalence of TH in this study was higher than previously reported. Overweight, age >or=10 years, and use of native L-asparaginase were significant predictors of TH.

Hemorrhagic disease of the newborn despite vitamin K prophylaxis at birth.

Late hemorrhagic disease of the newborn (HDN) presents 0.5-6 months after birth with mucocutaneous and intracranial bleeding. We describe here two cases of late HDN in infants who received vitamin K. The first case is a previously healthy breastfed male who received one dose of oral vitamin K at birth and developed an intracranial hemorrhage 5 weeks later. He was treated with intravenous vitamin K and recombinant factor VIIa prior to emergent craniectomy. An unrelated infant presented at 5 months of age with diarrhea and easy bruising despite IM vitamin K at birth. These cases illustrate the morbidity associated with late HDN.