Children's Hospital helps develop technique to improve survival from neuroblastoma

A new treatment for the deadly children's cancer neuroblastoma dramatically improves survival and has become part of the standard course of care even before results were published.

The study by researchers at Children's Hospital of Philadelphia and other top pediatric hospitals represents the first major improvement in survival for high-risk neuroblastoma in more than a decade, and the techniques involved might be adapted to other cancers such as melanoma.

The approach involves boosting the child's immune system and helping it target cancer cells. While effective, the treatment is painful for children; it also creates flulike symptoms and requires hospitalization to avoid complications.

The treatment was the subject of a study published Thursday in the New England Journal of Medicine. It shows that adding immunotherapy - revving up the child's immune system - increased two-year survival without relapse to 66 percent from 46 percent.

The results were so good that a year into the clinical trial, the independent panel overseeing the work decided it was no longer ethical to give some patients standard care as a comparison group. So all the patients got immunotherapy.

"It creates a new paradigm," said John M. Maris, director of the Center for Childhood Cancer Research at Children's Hospital. "This study establishes immunotherapy as a critical part of neuroblastoma treatment."

Allen Chen, director of pediatric bone-marrow transplantation at the Johns Hopkins Kimmel Cancer Center in Baltimore, said, "This is as close to a home run as any one trial gets, but it is far from the end of the story."

When the early results of the trial were shared within the pediatric-cancer community, Hopkins immediately added immunotherapy to its standard care of patients with high-risk neuroblastoma, said Chen, who was not involved in the study.

Despite the success, 32 of the 113 children receiving immunotherapy in the study relapsed, and 18 died. "There is still room for several more breakthroughs," Chen noted.

While rare, neuroblastoma causes 15 percent of all childhood cancer deaths. About 750 children a year are diagnosed with the disease, 300 to 400 with the high-risk form.

This week at Children's Hospital, Everest Grenke Leach, 5, of Michigan's rural Upper Peninsula, had already received the traditional regimen for neuroblastoma: chemotherapy followed by surgery, more chemo, radiation, and stem-cell transplants over eight months.

After all that, tests showed Everest was "NED" - no evidence of disease. But it still could return.

Some "cancer cells can hide out in the body often in the bone marrow," Maris said. Those hidden cancer cells are highly resistant to chemotherapy and radiation.

"If the disease comes back, there is very little hope of curing that patient," Maris said.

So on Wednesday morning, Everest began the second of five rounds of immunotherapy - a technique that involves attaching antibodies to cancer cells so they can be identified by the body's immune system and destroyed.

As with many cancer treatments, immunotherapy is hard on patients. The protein that the antibody targets is also found on nerve cells and the treatment hurts even with drugs to control the pain.

Chemicals are also infused to rev up the immune system, causing the children to experience flulike symptoms.

"Basically, we are giving these children the worst case of the flu they have ever had in their lives," Maris said.

But for Everest's parents, the prospect that the care could improve survival by 20 points is huge.

"Everest has worked so hard through all these other treatments, but again we are not quite there yet," said his mother, Liz Grenke Leach. "We never lived in the numbers and now we are going to celebrate this one. Everest deserves every extra percentage point he is going to get now."

At Children's Hospital, Maris and his colleagues continue to work on new treatments, building on the success of immunotherapy.

One approach is to genetically engineer the patient's own immune cells - T cells - to wipe out the cancer more effectively.

This treatment would be less toxic to the patients and would possibly improve outcomes, said Steven Grupp, director of translational research at the hospital's cancer research center.

But for now, Everest's mother is banking on the hospital's expertise as well as her son's ability to keep a positive attitude.

"He does have very hard days, but what amazes me is he keeps going, he keeps coming back," Grenke Leach said. "As a parent, you would do anything for your child, you would go to the ends of the Earth, and that is why this study is so important. Twenty percent is a big number."