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Cooper, TX, United States

French S.,University of California at San Francisco | Dubois S.G.,University of California at San Francisco | Horn B.,University of California at San Francisco | Granger M.,Cook Childrens Hospital | And 4 more authors.
Pediatric Blood and Cancer | Year: 2013

Background: 131I-metaiodobenzylguanidine (MIBG) produces a 37% response rate in relapsed/refractory neuroblastoma, and could be used to improve remission status prior to myeloablative chemotherapy with autologous stem cell transplant (ASCT). The purpose of our report was to evaluate safety and response with MIBG therapy followed by myeloablative busulfan and melphalan (BuMel) with ASCT in patients with refractory neuroblastoma. Methods: Retrospective chart review was done on patients treated with MIBG (18mCi/kg) on Day 1 and ASCT on Day 14. Six to eight weeks after MIBG, patients without progressive disease received IV busulfan on Days -6 to -2 (target Css 700-900), melphalan (140mg/m2 IV) on Day -1, and ASCT on Day 0. Response and toxicity were evaluated after MIBG and again after myeloablative therapy. Results: Eight patients completed MIBG/ASCT followed by BuMel/ASCT. MIBG was well tolerated, with Grade 3 or 4 non-hematologic toxicity limited to one patient with sepsis. Grade 3 mucositis occurred in six patients after BuMel/ASCT. One patient developed sinusoidal obstructive syndrome (SOS) and died 50 days post-ASCT following myeloablative conditioning. All patients engrafted neutrophils (median 16.5 days) and platelets (median 32 days) after BuMel, excluding the patient with SOS. After all therapy, there were three complete, two partial, and one minor response in seven evaluable patients. Conclusions: MIBG at doses up to 18mCi/kg can be safely administered 6 weeks prior to a BuMel consolidative regimen for refractory neuroblastoma. Preceding MIBG did not impair engraftment following BuMel. This regimen is being further evaluated in a Children's Oncology Group (COG) trial. © 2012 Wiley Periodicals, Inc.


Zhang J.,St Jude Childrens Research Hospital | Mullighan C.G.,St Jude Childrens Research Hospital | Harvey R.C.,University of New Mexico | Wu G.,St Jude Childrens Research Hospital | And 17 more authors.
Blood | Year: 2011

We sequenced 120 candidate genes in 187 high-risk childhood B-precursor acute lymphoblastic leukemias, the largest pediatric cancer genome sequencing effort reported to date. Integrated analysis of 179 validated somatic sequence mutations with genome-wide copy number alterations and gene expression profiles revealed a high frequency of recurrent somatic alterations in key signaling pathways, including B-cell development/ differentiation (68% of cases), the TP53/RB tumor suppressor pathway (54%), Ras signaling (50%), and Janus kinases (11%). Recurrent mutations were also found in ETV6 (6 cases), TBL1XR1 (3), CREBBP (3), MUC4 (2), ASMTL (2), and ADARB2 (2). The frequency of mutations within the 4 major pathways varied markedly across genetic subtypes. Among 23 leukemias expressing a BCRABL1-like gene expression profile, 96% had somatic alterations in B-cell development/ differentiation, 57% in JAK, and 52% in both pathways, whereas only 9% had Ras pathway mutations. In contrast, 21 cases defined by a distinct gene expression profile coupled with focal ERG deletion rarely had B-cell development/ differentiation or JAK kinase alterations but had a high frequency (62%) of Ras signaling pathway mutations. These data extend the range of genes that are recurrently mutated in high-risk childhood B-precursor acute lymphoblastic leukemia and highlight important new therapeutic targets for selected patient subsets.


Honeycutt J.H.,Cook Childrens Hospital
Seminars in Plastic Surgery | Year: 2014

Over the last decade, endoscopy has been increasingly utilized in craniosynostosis surgery. In 2006, the author added endoscopy followed by helmet therapy to the treatment of young craniosynostosis patients. Since then, 73 children have been successfully treated utilizing endoscopic techniques with a transfusion rate of 23%. Most children are discharged on the first postoperative day; helmet therapy begins one week later. A helmet is worn for 4 to 6 months with one helmet replacement. Complications were limited to three reoperations to address suboptimal results, and one reoperation for a persisting skull defect. One sagittal sinus injury was addressed successfully, with resolution of a small intrasinus thrombus and no adverse brain sequelae. Although not applicable to every craniosynostosis patient, properly applied endoscopic-assisted craniosynostosis surgery is safe and effective, adding another option to the treatment armamentarium for craniosynostosis. © 2014 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York.


Vichinsky E.,Childrens Hospital Oakland Research Institute | Torres M.,Cook Childrens Hospital | Minniti C.P.,U.S. National Institutes of Health | Barrette S.,Sainte Justine Hospital | And 3 more authors.
American Journal of Hematology | Year: 2013

We report a prospective, randomized, Phase II study of deferasirox and deferoxamine (DFO) in sickle cell disease patients with transfusional iron overload, with all patients continuing on deferasirox after 24 weeks, for up to 2 years. The primary objective was to evaluate deferasirox safety compared with DFO; long-term efficacy and safety of deferasirox was also assessed. We also report, for the first time, the safety and pharmacokinetics of deferasirox in patients concomitantly receiving hydroxyurea. Deferasirox (n=135) and DFO (n=68) had comparable safety profiles over 24 weeks. Adverse events (AEs) secondary to drug administration were reported in 26.7% of patients in the deferasirox cohort and 28.6% in the DFO cohort. Gastrointestinal disorders were more common with deferasirox, including diarrhea (10.4% versus 3.6%) and nausea (5.2% versus 3.6%). The most common AE in the DFO group was injection-site pain irritation, which occurred in 7% of patients. Acute renal failure occurred in one patient on deferasirox who was continued on medication despite progressive impairment of renal function parameters. Serum ferritin levels were reduced in both treatment groups. Patients continuing on deferasirox for up to 2 years demonstrated an absolute median serum ferritin decrease of -614 ng/mL (n=96). Increasing deferasirox dose was associated with improved response and a continued manageable safety profile. Concomitant hydroxyurea administration (n=28) did not appear to influence the efficacy, safety (including liver and kidney function), and pharmacokinetic parameters of deferasirox. © 2013 Wiley Periodicals, Inc.


Brooks M.R.,Cook Childrens Hospital | Golianu B.,Stanford University
Paediatric Anaesthesia | Year: 2016

Children with chronic pain often undergo surgery and effective perioperative management of their pain can be challenging. Identification of the pediatric chronic pain patient preoperatively and development of a perioperative pain plan may help ensure a safer and more comfortable perioperative course. Successful management usually requires multiple different classes of analgesics, regional anesthesia, and adjunctive nonpharmacological therapies. Neuropathic and oncological pain can be especially difficult to treat and usually requires an individualized approach. © 2016 John Wiley & Sons Ltd

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