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Tandem High-Dose Therapy in Rapid Sequence for Children With High-Risk Neuroblastoma

From the Division of Oncology, Department of Pediatrics, Children’s Hospital of Philadelphia, University of Pennsylvania, School of Medicine, Philadelphia, PA; Diagnostics Division, Nexell Therapeutics, Inc, Irvine, CA; Emory University, Atlanta, GA; Primary Children’s Hospital, University of Utah Health Sciences Center, Salt Lake City, UT; Department of Pediatric Oncology, Dana-Farber Cancer Institute; Departments of Medicine and Surgery, Children’s Hospital; and Division of Pediatric Hematology-Oncology, Massachusetts General Hospital, Boston, MA; and Memorial Blood Centers of Minnesota and University of Minnesota, Minneapolis, MN.

Address reprint requests to Stephan Grupp, MD, PhD, Children’s Hospital of Philadelphia, 324 S 34th St, Abramson 902, Philadelphia, PA 19104; email grupp{at}email.chop.edu

PURPOSE: Advances in chemotherapy and supportive care have slowly improved survival rates for patients with high-risk neuroblastoma. The focus of many of these chemotherapeutic advances has been dose intensification. In this phase II trial involving children with advanced neuroblastoma, we used a program of induction chemotherapy followed by tandem high-dose, myeloablative treatments (high-dose therapy) with stem-cell rescue (HDT/SCR) in rapid sequence.

PATIENTS AND METHODS: Patients underwent induction chemotherapy during which peripheral-blood stem and progenitor cells were collected and local control measures undertaken. Patients then received tandem courses of HDT/SCR, 4 to 6 weeks apart. Thirty-nine patients (age 1 to 12 years) were assessable, and 70 cycles of HDT/SCR were completed.

RESULTS: Pheresis was possible in the case of all patients, despite their young ages, with an average of 7.2 x 10⁶ CD34⁺ cells/kg available to support each cycle. Engraftment was rapid; median time to neutrophil engraftment was 11 days. Four patients who completed the first HDT course did not complete the second, and there were three deaths due to toxicity. With a median follow-up of 22 months (from diagnosis), 26 of 39 patients remained event-free. The 3-year event-free survival rate for these patients was 58%.

CONCLUSION: A tandem HDT/SCR regimen for high-risk neuroblastoma is a feasible treatment strategy for children and may improve disease-free survival.

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