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High-Risk Neuroblastoma Treated With Tandem Autologous Peripheral-Blood Stem Cell–Supported Transplantation: Long-Term Survival Update

Rani E. George, Shuli Li, Cheryl Medeiros-Nancarrow, Donna Neuberg, Karen Marcus, Robert C. Shamberger, Michael Pulsipher, Stephan A. Grupp, Lisa Diller

From the Departments of Pediatric Oncology and Biostatistics and Computational Biology, Dana-Farber Cancer Institute; Departments of Medicine, Radiation Oncology, and Surgery, Children's Hospital Boston, Boston, MA; Division of Oncology, Primary Children's Medical Center, Salt Lake City, UT; and the Division of Oncology, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA

Address reprint requests to Rani George MD, PhD, MRCP, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Dana 322, 44 Binney St, Boston, MA 02115; e-mail: rani_george{at}dfci.harvard.edu

PURPOSE: To provide an update on long-term survival of patients with high-risk neuroblastoma treated with tandem cycles of myeloablative therapy and peripheral-blood stem-cell rescue (PBSCR).

PATIENTS AND METHODS: Ninety-seven patients with high-risk neuroblastoma were treated between 1994 and 2002. Patients underwent induction therapy with five cycles of standard agents, resection of the primary tumor and local radiation, and two consecutive courses of myeloablative therapy (including total-body irradiation) with PBSCR.

RESULTS: Fifty-one patients have experienced relapse or died. Median follow-up time among the 46 patients who remain alive without progression is 5.6 years (range, 15.1 months to 9.9 years). Progression-free survival (PFS) rate at 5 years from diagnosis was 47% (95% CI, 36% to 56%), and PFS rate at 7 years was 45% (95% CI, 34% to 55%). Overall survival rate was 60% (95% CI, 48% to 69%) and 53% (95% CI, 40% to 64%) at 5 and 7 years, respectively. The 5- and 7- year PFS rates from time of first transplantation for 82 patients who completed both transplants were 54% (95% CI, 42% to 64%) and 52% (95% CI, 40% to 63%), respectively. Five patients died from treatment-related toxicity after tandem transplantation. Relapse occurred in 37 (42%) of 89 patients, mainly within 3 years of transplantation and primarily in diffuse osseous sites. No primary CNS relapse or secondary leukemia was seen. One patient developed synovial cell sarcoma 8 years after therapy.

CONCLUSION: High-dose therapy with tandem autologous stem-cell rescue is effective for treating high-risk neuroblastoma, with encouraging long-term survival. CNS relapse and secondary malignancies are rare after this therapy.

Supported in part by the Fred Lovejoy Resident Research Award (R.E.G.), Grant No. NIH R21 CA110516, and funds from the Sanford and WW Smith Trusts (S.A.G.).

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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