Things looked bleak for Emma Brooke Whitehead.
The 6-year-old had acute lymphoblastic leukemia, and the cancer looked terminal. Two years of chemotherapy had little effect. Doctors at the Children’s Hospital of Philadelphia (CHOP) estimated that she had a month to live.
Because of her unlikely chance for survival, Emma’s doctors decided to take a huge risk: They injected her with a genetically modified HIV stripped of its capacity to induce AIDS and modified to turn millions of Emma’s T-cells into so-called “serial killer cells” that would destroy the cells ravaging her body. The modified cells attached themselves to the cells possessing a cancer antigen called CD-19, which attach themselves to the lymphocytes in leukemia patients, and destroy those cells.
Eight months later, Emma appears to be cured.
“There is no danger of infection and there is no longer the HIV virus,” said researcher Dr. Stephen Grupp, a pediatric oncologist at CHOP. “She has no leukemia in her body for any test that we can do — even the most sensitive ones.”
Emma’s mother even said the girl now has the energy to play with her dog, go to school, even play soccer. Meanwhile, researchers say that they will continue to investigate whether modified HIV can be used to target and destroy other cancer antigens.
While Emma Whitehead’s is a particularly sensational case, researchers are making new discoveries every day in the treatment of pediatric cancer.
“There’s constantly research going on, not only to improve survival, but to improve quality of life,” said Dr. Karol Kerr, a pediatric oncologist and supervisor of the Children’s Oncology Group at Upstate Golisano Children’s Hospital. “Additionally, a lot of the research focuses on decreasing the long-term side effects of treatment.”
Treatment methods
The most advancements, Kerr said, have been made in the treatment of childhood leukemia and lymphoma.
“With children, there’s a lot of ground to be covered in brain tumors and solid tumors,” she said. “There have certainly been improvements, but nowhere near the gains we’ve made with leukemia.”
And the biggest leaps have been made since the advent of chemotherapy, which basically works by attacking rapidly growing cells and damaging their DNA.
“Essentially cancer cells are cells that do not go through programmed death,” Kerr said. “Our cells have a limited life span, and we’re constantly renewing ourselves. But in cancer cells, they just grow and divide unchecked. Traditional chemotherapy attacks cells in your body that grow rapidly, not just cancer cells; many of your normal cells are affected. This is the reason for a lot of the side effects like hair loss. Nausea is common because chemotherapy affects the lining of the stomach.”
The era of chemotherapy began after World War II, when the U.S. Army was studying the chemicals used in mustard gas to develop protective measures. That work led to the discovery of a compound called nitrogen mustard, which was found to work against lymphomas. Not long after, scientist Sidney Farber discovered that aminopterin, a compound related to folic acid, could lead children with leukemia into remission.
These early studies resulted in the development of a variety of drugs that block cell replication and growth functions. Those drugs first cured metastatic cancer in 1956 and have since been used to treat people with all kinds of cancer. According to the American Cancer Society, long-term remissions and even cures of many patients with Hodgkin disease and childhood ALL (acute lymphoblastic leukemia) with chemotherapy were first reported during the 1960s. Since physicians started using chemotherapy in the treatment of leukemia and lymphoma, survival rates have skyrocketed.
“Childhood leukemia today has a high cure rate,” Kerr said. “If you looked at the five-year survival rates in 1960, they were about 30 to 40 percent. There was a big leap in the 1970s with the advent of chemotherapy; the survival rates then went up to about 60 percent. Now, with leukemia in general, we’re looking at survival rates in the 80s, with the most common type [having a survival rate] in the 90s.”
Children with leukemia typically get chemotherapy only, but children with other kinds of cancer, including brain tumors and other solid tumors, are also treated with radiation therapy.
“Radiation is considered local control, whereas chemotherapy is systemic. Radiation is localized,” Kerr said. “It’s targeted directly to the site of certain types of cancer, which is why it is rarely used in leukemia, which is more of a systemic cancer. It’s used for children with isolated lymphomas or brain tumors.”
Radiation was discovered by German physics professor Wilhelm Conrad Roentgen in 1896. Within three years, it was being used to treat cancer as it was discovered that it could greatly improve the patient’s chance for a cure.
Physicians had to be careful when using radiation in those early days, because it could also cause cancer. Many early radiologists used the skin of their arms to test the strength of radiation from their radiotherapy machines, looking for a dose that would produce a sunburn-like pink reaction. This was considered an estimate of the proper daily fraction of radiation. However, many of those doctors developed leukemia.
Since then, radiation therapy has become more precise, targeting tumors without harming the cells around them. According to the American Cancer Society, there are several types of therapy used in cancer patients: Conformal radiation therapy (CRT) uses CT images and special computers to very precisely map the location of a cancer in three dimensions. The patient is fitted with a plastic mold or cast to keep the body part still and in the same position for each treatment. The radiation beams are matched to the shape of the tumor and delivered to the tumor from several directions. Intensity-modulated radiation therapy (IMRT) is like CRT, but along with aiming photon beams from several directions, the intensity (strength) of the beams can be adjusted. This gives even more control over decreasing the radiation reaching normal tissue while delivering a high dose to the cancer. Conformal proton beam radiation therapy uses proton beams that cause little damage to tissues they pass through but effectively kill cells at the end of their path. Radiation can also be used at the time of surgery directly on nearby tissues after a tumor has been removed. In many cases, patients are dosed with so-called radiosensitizers that make cancer more sensitive to radiation.
The research
Meanwhile, researchers are forever seeking better, more effective ways to treat cancer, as well as to improve the quality of life of patients and limit the side effects of treatment. Most of this research is conducted through clinical trials in which new treatments are tested on patients. The trials compare new treatments to standard treatments and test theories about cancer learned in the laboratory for clinical observation on patients.
“A majority of children within the United States are treated via a protocol developed by the Children’s Oncology Group, which is an international group of pediatric oncologists,” Kerr said. “The goal is to provide the most optimal and most effective treatment with the least amount of side effects.”
At Upstate Golisano Children’s Hospital’s William J. Waters Center for Children’s Cancer and Blood Disorders, Kerr coordinates all of the clinical trials.
“There are different phases of clinical trials,” she said. “In a Phase III trial, the question is how effective is a combination of known therapies. In that case, we know what most of the side effects are. In Phase II, we know how the drugs work and what the side effects are, but we don’t know the dose, so it’s a dose-binding trial. In Phase I, we’re not sure of the effectiveness or side effects. It may be a drug that’s been utilized in adults but not kids, or it may be a brand-new trial like the girl at the Children’s Hospital of Philadelphia. Usually there is a very limited number of patients involved in those studies. It’s a last-resort kind of therapy.”
Research is conducted by physicians within the Children’s Oncology Group nationwide, and independently at larger hospitals such as Dana Farber in Boston and Sloan Kettering in New York City .
The problem, Kerr said, is that very little government funding is allocated to pediatric cancer research.
“Unfortunately, even though up to 3,000 kids are diagnosed with cancer every year, less than 10 percent of the national budget for research at the National Cancer Institute goes to childhood cancer research,” she said. “That’s why we rely a lot on private organizations like St. Baldrick’s or CureSearch.”
But the research being conducted is promising. Scientists have made advancements in immune-based therapy, which uses the body’s own immune system to attack cancer cells. Emma Whitehead’s case is a prime example of the success of those kinds of therapies. Researchers are also looking into the promising field of stem cell research.
Complementary care
While researchers work toward a cure, physicians and nurses in the trenches are working to improve the treatment of the whole child.
“We provide a lot of extra care for our kids,” Kerr said. “We use what we call a team approach, so it’s not just physicians and nurses, but also the Child Life Specialist who’s involved from the very beginning, the music and art therapists, our family therapist, our social worker — there are many people who get involved to provide the care they need.”
Sometimes the care the child needs comes in the form of complementary and alternative medicine (CAM). A study in the journal Pediatrics found that the use of CAM was widespread in pediatric cancer patients; depending on the type of therapy, anywhere from 6 to 91 percent of patients used CAM strategies including herbal remedies, megavitamins and diet and nutrition adjustments. The study did not indicate if the children were replacing traditional therapy with alternative methods, but Kerr said CAM is often used in conjunction with chemotherapy and radiation.
“There’s a lot of work being done to determine how they help decrease side effects,” Kerr said. “If a family wants to use these kinds of products, we encourage families to bring in the medicines to talk about them, because some of them are contraindicated and they’ll actually interfere with the chemotherapy.”
Kerr said that there are a number of products that can improve the way a child feels during treatment.
“There are a lot of things that reduce mucositis [inflammation of the lining of the gastrointestinal tract] and promotes the healing process,” Kerr said. “There are a number of products out there that work on decreasing skin breakdown, various lotions and skin care. There’s a lot of mouth care to prevent the side effects of therapy. There is not a lot of scientific data about high-dose vitamins; some can counteract the chemotherapy. Again, we encourage families to bring these in and talk to their doctors. Some of them are definitely worthwhile, but some can be harmful.”
All in all, advancements in science have not only improved survival rates, but also helped children living with cancer to live more normal, comfortable lives.
“We’ve made a lot of great steps, especially in supportive care measures,” Kerr said. ‘I saw a lot of kids suffer through the nausea from chemotherapy before the drugs we use now every day. There have been some great topical anesthetics developed that we didn’t have years ago. We’ve improved this multidisciplinary approach to children’s cancer, so that they have access to the music therapist, the physical therapist, the occupational therapist, the nutritionist — we’re treating the whole child from the start instead of bringing them in to do cleanup when there’s a problem. There have been a lot of changes in the way we approach the entire family so that they become part of the team, which is very important.”
This story is part of a four-part series on families facing a pediatric cancer diagnosis. Future installments will include what happens when a child goes into remission and community resources for families and patients. If you would like to contribute to this series, please contact Sarah Hall at [email protected].
