High-Risk Neuroblastoma

Neuroblastoma is one of the most common types of solid tumors in childhood. While many children with neuroblastoma may be cured with surgical removal of the tumor and chemotherapy treatments, those with extensive disease and/or features that indicate a very high likelihood of recurrence (often referred to as high risk) may not respond as well to this standard therapy.

Autologous BMT for children with high risk neuroblastoma

The UCSF Pediatric BMT Program offers autologous bone marrow stem cell transplantation to treat children with high risk neuroblastoma. In this type of transplant, high dose chemotherapy used during a conditioning period is given to kill the tumor. Bone marrow function is then restored by infusing the patient's own previously-stored bone marrow cells. One advantage to this approach is that the risk of graft versus host disease is eliminated.

Because the majority of these children have neuroblastoma cells in their bone marrow, special techniques have been developed to remove (or purge) these cancer cells from the bone marrow stem cell collection before re-infusion. The purged, or purified, bone marrow stem cells are stored in liquid nitrogen until the day of transplant. More recently, this purging technique has been adapted to treat circulating bone marrow stem cells in the blood that have been collected by a procedure called leukapheresis for a peripheral blood stem cell transplant (PBSC). There are some data to suggest that purging is not necessary with PBSC collections. Currently, the UCSF Pediatric BMT Program is participating in a national study conducted by the Childrens Oncology Group that is evaluating the efficacy of PBSC purging in patients with newly diagnosed high risk neuroblastoma.

In addition, novel research protocols are available for children who have either failed to respond to initial chemotherapy following diagnosis or who have relapsed after an initial response. These children are not candidates for the standard autologous transplant but may be eligible for combined targeted radiation therapy followed by an autologous transplant.

High-Risk Neuroblastoma and MIBG

High risk metastatic neuroblastoma that does not initially respond to chemotherapy or progresses after initial chemotherapy treatment is usually unresponsive to further treatment, even with therapy that includes intensive chemotherapy and bone marrow stem cell transplantation. New approaches are needed for such resistant tumors. MIBG is a chemical that mimics certain natural compounds in the body that are concentrated in selective tissues including neuroblastoma cells. ¹³¹I is an isotope of iodine that emits powerful radioactive energy, sufficient to kill tumor cells. ¹³¹I can be chemically attached to MIBG to form a compound that holds promise for cell-specific treatment of neuroblastoma. Under the leadership of Dr. Katherine Matthay, treatment with ¹³¹I-MIBG alone was evaluated at UCSF in children with progressive or relapsed neuroblastoma. The tumors in 20-40% of these children decreased in size in response to this therapy. The major toxicity that was seen was a suppression of normal marrow function, which could be corrected by autologous stem cell transplant. Significant organ toxicity outside the bone marrow has yet to be seen.

Based on these observations we believe that doses of ¹³¹I-MIBG can be increased with the support of autologous bone marrow rescue or peripheral blood stem cell rescue. Furthermore, we believe that by combining higher doses of ¹³¹I -MIBG with high dose chemotherapy followed by an autologous bone marrow stem cell transplant, children with otherwise untreatable neuroblastoma will have a chance at long term survival with less toxicity than has previously been seen.