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Background The high prevalence of carboplatin hypersensitivity reactions (HSR) significantly affects the treatment of pediatric patients with low-grade glioma (LGG). Rechallenging patients is an option that must balance the risks of repeat allergic reaction to the benefits of retaining an effective anti-tumor regimen. Procedure We performed a retrospective review of children with LGG treated with carboplatin and vincristine between October 2000 and April 2013, who had a documented HSR to carboplatin. Patients were re-exposed to carboplatin using either precautionary measures (prolonged infusion time and premedication with H1 antagonists, H2 antagonists, and corticosteroids), a desensitization protocol, or both. Results We report the results of our institutional experience of carboplatin re-exposure using both premedication with a prolonged infusion time and a desensitization protocol. Overall, 40 of 55 (73%) patients were successfully rechallenged with carboplatin, including 19 of 25 (76%) patients who underwent desensitization. Conclusion Our results demonstrate re-exposure to be a safe alternative to abandoning carboplatin for patients with a hypersensitivity reaction. We propose a clinical algorithm for treatment. Pediatr Blood Cancer 2015; 9999:1–6 © 2015 Wiley Periodicals, Inc.

Background The prognosis for recurrent or refractory brain tumors in children is poor with conventional therapies. Topotecan is a topoisomerase I inhibitor with good central nervous system (CNS) penetration following oral administration. Increased efficacy of topotecan has been demonstrated with prolonged low-dose daily treatment in pre-clinical models. To investigate further this drug delivered orally in pediatric CNS malignancies, a phase II study in children with recurrent or refractory brain tumors was performed. Procedure Patients ≤21 years of age at diagnosis with a recurrent, progressive, or refractory primary CNS malignancy and measurable disease, were eligible. Patients enrolled into four strata: ependymoma (N = 4), high-grade glioma (HGG) (N = 6), brainstem glioma (BSG) (N = 13), and primitive neuroectodermal tumor (PNET) (N = 8). Oral topotecan was administered once daily at a dose of 0.8 mg/m2/day for 21 consecutive days repeated every 28 days. Response and toxicity profiles were evaluated. Results Twenty-six patients were evaluable (median age 9.2 years; 10 males). Two objective responses were observed in PNET patients with disseminated tumor at study entry. These two patients remain alive and in remission 7 and 9.5 years off study. Four other patients (two BSG, one PNET, and one HGG) had stable disease (median 4.6 months). The most common toxicities were hematologic. Conclusions Daily oral topotecan at a dose of 0.8 mg/m2/day can be safely administered to children with recurrent or refractory brain tumors. This regimen identified activity in recurrent PNET. The prolonged progression free survival (PFS) in two PNET patients justifies consideration of this regimen in more advanced clinical trials. Pediatr Blood Cancer. 2010;56:39–44. © 2010 Wiley-Liss, Inc.

Background Opioids are a cornerstone of palliation of pain. We sought to assess variation in opioid prescription during the last week of life among a cohort of pediatric oncology patients who died while hospitalized. Procedure We used detailed hospital administrative data from the Pediatric Health Information System (PHIS) regarding 1,466 subjects 0–24 years of age who were treated at 33 hospitals between 2001 and 2005. Results Among the 1,466 subjects hospitalized at the time of their death, 56% received opioids every day during the hospitalized portion of their last week of life, while 44% did not. This proportion varied substantially across hospitals (range 0–90.5%). After multivariate adjustment for individual-level characteristics, the hospital-level effect on the odds of continuous prescription of opioids during the hospitalized portion of the last 7 days of life continued to vary significantly among hospitals, accounting for 10.5% of the variance in the receipt of daily opioid (P

Background: The purpose of this study is to investigate the efficacy of an intensive chemotherapy induction regimen followed by myeloablative chemotherapy and autologous hematopoietic stem cell rescue (AHSCR) in children with newly diagnosed ependymoma. Patients and Methods: Twenty-nine children less than 10 years of age at diagnosis of ependymoma were enrolled on the “Head Start” studies. Twenty-four patients with localized disease received an induction regimen including five cycles of chemotherapy (cisplatin, vincristine, etoposide cyclophosphamide, and high dose methotrexate for patients with metastatic disease). Following induction, individuals without evidence of disease proceeded to marrow-ablative chemotherapy (thiotepa, carboplatin, and etoposide) with AHSCR. Results: The estimated 5-year event free survival (EFS) and overall survival (OS) from diagnosis were 12% (±6%) and 38% (±10%), respectively. The toxic mortality amongst this group of 29 patients was 10.3%. Younger age (less than 18 months at diagnosis) was the only statistically significant prognostic factor. The estimated 5-year OS rate for the five patients with metastatic disease at presentation was 80% (±18%). Overall, radiation-free survival at 5 years from diagnosis was 8% (±5%). Conclusions: The use of an intensive induction chemotherapy regimen including myeloablative chemotherapy followed by AHSCR in newly diagnosed young children with ependymoma is not superior to other previously reported chemotherapeutic strategies. Pediatr Blood Cancer 2007;49:34–40. © 2006 Wiley-Liss, Inc.