Using Tandem Transplants to Treat Neuroblastoma

For many years, less than half of children diagnosed with high-risk neuroblastoma, a cancer that starts in immature nerve cells, would be expected to live 5 or more years after diagnosis. Pediatric oncologist and researcher Julie Park has devoted her career to try to change that. In 2016, Julie and her colleagues demonstrated encouraging improvements using a new approach to treat high-risk neuroblastoma in an NCI-sponsored clinical trial that changed the way the disease is treated in the United States. The trial was conducted by the Children’s Oncology Group (COG), part of NCI’s National Clinical Trials Network.

One of the 652 children who participated in the trial was Katie Belle of Seattle, who was 3½ years old in 2009, when doctors found a baseball-sized tumor in her abdomen that turned out to be high-risk neuroblastoma. Katie was given a 35% chance of survival, and, on the advice of doctors, her parents immediately enrolled her in the COG trial. “When we signed Katie up, there didn’t seem to be a lot of novel, promising ideas to pursue,” said her mother Jennifer Belle, who serves as a patient advocate on COG’s Neuroblastoma Committee.

Before the COG trial, the standard treatment for high-risk neuroblastoma was a single-transplant approach that involved high-dose chemotherapy to destroy as many cancer cells as possible, followed by an autologous (self-donating) blood stem cell transplant. The stem cell transplant is needed because the intense chemotherapy also destroys blood-forming stem cells in the patient’s bone marrow. The stem cells used for the transplant are collected from the patient’s blood and then given back to the patient once the chemotherapy is completed. The transplanted cells then repopulate the patient’s bone marrow and restore its ability to produce red and white blood cells and platelets. Prior clinical trials conducted by COG demonstrated that this treatment approach improved the 5-year survival rate for children with high-risk neuroblastoma from 25% in the 1990s to just less than 50% by the early 2000s.

The new approach in the recent COG trial was to double-up that treatment, with the hopes of increasing the percentage of patients who would benefit from this intense therapy. In the trial, one group of patients received the standard treatment (chemotherapy and a stem cell transplant followed by another round of chemotherapy and a second, or tandem, stem cell transplant). After 3 years of follow-up, 61% of the patients who received a tandem transplant were alive and cancer-free, compared with 48% of those who received only a single transplant.

Katie was among the patients who received a tandem transplant. More than 5 years later, she remains cancer free. Although she is generally in good health now, Katie did experience side effects from the treatment, including sterility and thyroid dysfunction. Jennifer worries about her future. “We don’t know what the other long-term complications will be,” she said. Julie added, “The therapies for high-risk neuroblastoma are among the most toxic therapies given to kids.”

Tandem transplants have now become the standard of care for high-risk neuroblastoma. “Through continued research, we keep moving the needle and improving survival,” Julie reflected. “The next step is to find treatments that will be less toxic and more effective.” To this end, COG researchers hope to capitalize on advances in molecular biology and immunology research to find additional targets and improve the quality of life for children like Katie.