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Please note: This article is part of the Cancer Center's News Archive and is here for historical purposes. The information and links may no longer be up-to-date.

Michigan Oncology Journal Summer 1999

New Approaches for Neuroblastoma

Raymond Hutchinson, M.D.,
Professor of Pediatrics
Clinical Director, Pediatric BMT Program

Children rarely develop cancer, but when they do, treatment often is successful. That, indeed, is good news. Unfortunately, several childhood cancers remain highly lethal; metastatic neuroblastoma is one of the most deadly.

Approximately half of the children diagnosed with neuroblastoma have metastases at the time of diagnosis (1). Furthermore, in half of all children who are diagnosed with neuroblastoma by their second birthday, the impact upon families and society is greater than first impressions might suggest. Only one in five children older than one year of age with metastatic neuroblastoma survives (1).

Stem Cell Transplants
The use of high-dose chemo-radiotherapy followed by autologous bone marrow infusion has gained wide acceptance in the treatment of newly diagnosed patients with chemotherapy-sensitive, metastatic neuroblastoma and in patients with disease recurrence following initial chemotherapy (2,3). A trial recently completed by the ChildrenŐs Cancer Group (in which the University of MichiganŐs Pediatric Oncology Program participated) demonstrated improved disease-free survival for children with advanced neuroblastoma after high-dose chemo-radiotherapy and autologous bone marrow transplant versus children continuing on standard-dose chemotherapy (4).

Pediatric oncologists and bone marrow transplant physicians at the University of Michigan Cancer Center (UMCC) are applying this promising technology to the unfortunate children afflicted by advanced neuroblastoma. A total of 28 autologous stem cell transplants have been performed for children with advanced neuroblastoma; disease-free survival at four years is 30% (see Figure 1).

MIBG Trial
Because there is plenty of room for improvement, innovative treatment approaches are being developed at UMCC. Dr. Greg Yanik recently initiated a transplant trial in which a tumor-targeted radiotherapeutic agent, 131I-metaiodobenzylguanidine (131I-MIBG), is used to deliver radiation therapy in place of standard total body irradiation. This agent concentrates selectively in tissues of adrenergic origin (e.g., the adrenal medulla) and in tumors that arise in such tissues (e.g., neuroblastoma). Prior phase I and II trials of 131I-MIBG at the University of Michigan and elsewhere have demonstrated the safety and the therapeutic activity of this treatment modality (5,6). Dr. Yanik and his colleagues hope that the 131I-MIBG will effectively deliver radiation therapy to the tumor sites, while sparing the non-involved surrounding tissues. If proven effective, Dr. Yanik's approach will increase the therapeutic index of autologous transplant for advanced neuroblastoma. This trial is currently accruing patients at the first of three planned dose levels of 131I-MIBG.

Vaccine Trial
In a related area, my colleague Jim Geiger, M.D., and I are conducting a phase I trial of tumor cell vaccination for children with refractory neuroblastoma. Similar trials conducted at other medical centers indicate that tumor immunization strategies can produce anti-tumor effects (7-9). The UMCC trial utilizes autologous tumor and autologous antigen presenting cells (dendritic cells) to promote and augment in vivo anti-neuroblastoma immune response. A series of three intradermal immunizations at two-week intervals is completed for each patient, monitoring for adverse reactions and for anti-tumor efficacy. This trial is in an early stage as well and is currently accruing patients. Eventually, this approach may be used following stem cell transplant to treat minimal residual disease, thereby hopefully increasing the percentage of patients with long-term, disease-free survival.

Through the combined efforts of UMCC investigators, new avenues to treat neuroblastoma are being explored. Hopes are high that new inroads will be made into the successful treatment of this dreaded disease.

To refer a patient to one of the above protocols, please call 800-865-1125.

References

  1. Brodeur GM, Castleberry RP, et al. Neuroblastoma, in Pizzo PA, Poplack DG (eds): Principles and Practice of Pediatric Oncology (2nd ed.). Philadelphia, PA. J.B. Lippincotte Co., p 739, 1993.
  2. Philip T, Ladenstein R, Zucker JM, et al. Double megatherapy and autologous bone marrow transplantation for advanced neuroblastoma: the LMCE2 study. Br J Cancer. 67:119, 1993.
  3. Graham-Pole J, Casper J, Elfenbein G, et al. High-dose chemoradiotherapy supported by marrow infusions for advanced neuroblastoma: a Pediatric Oncology Group study. J Clin Oncol. 9:152, 1991.
  4. Matthay KK, Harris R, Reyolds CP, et al. Improved event-free survival (EFS) for autologous bone marrow transplantation (ABMT) vs. chemotherapy in neuroblastoma: a phase III randomized Children's Cancer Group (CCG) study. Proc Am Soc Clin Oncol. 17:525a, 1998.
  5. Sisson JC, Shapiro B, Hutchinson RJ, Carey JE, Zasadny KR, Zempel SA, Normolle DP. Predictors of toxicity in treating patients with neuroblastoma by radiolabeled metaiodobenzylguanidine. Eur J Nucl Med. 21:46, 1994.
  6. Hutchinson RJ, Sisson JC, Shapiro B, Miser JS, Normolle D, Shulkin BL, Francis IR, Zasadny K, Carey JE, Johnson JW, Mallette SA, Mudgette B. 131-1-Metaiodobenzylguanidine treatment in patients with refractory advanced neuroblastoma. Am J Clin Oncol. (CCT). 15(3): 226, 1992.
  7. Hsu FJ, Benike C, Fagnoni F, et al. Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nat Med. 2:52, 1996.
  8. Hsu FJ, Caspar CB, Czerwinski D, et al. Tumor-specific idiotype vaccines in the treatment of patients with B-cell lymphoma: long-term results of a clinical trial. Blood. 89:3129, 1997.
  9. Reichardt VL, Okada CY, Liso A, et al. Idiotype vaccination using dendritic cells after autologous peripheral blood stem cell transplantation for multiple myeloma: a feasibility study. Blood. 93:2411, 1999.

Figure 1. Disease-free survival (patients alive without recurrence) of 28 patients with advanced neuroblastoma following autologous transplantation.

 

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Please note: The articles listed in the Cancer Center's News Archive are here for historical purposes. The information and links may no longer be up-to-date.