In late June 2003, shortly before her second birthday, Emily Wang came down with a low-grade fever that lasted for two straight weeks. It was during this time that Emily's grandmother first noticed that her belly was distended and hard to the touch. Emily also often complained of leg pains. “She was very needy and constantly wanted Mommy to carry her,” Emily's mother, Tina, explains. “It was so unlike her because she was usually an outgoing and independent little girl.”
Emily loved playing in the water, so when the Wangs visited Tina's sister's house over the July Fourth weekend they set up a small pool for Emily. But when they attempted to put her into the water, Emily cried and refused to play in the pool. “We all thought that it was very strange of her to react in such a way,” Tina remembers. “When we watch the video we took that day, we wonder why we didn't see the obvious signs that she was unwell.”
Worse Than Expected
Suspecting that there might be something seriously wrong with Emily, the Wangs made an appointment with her pediatrician on July 7. At the appointment, they described the symptoms, and after examining Emily's distended abdomen the doctor said that it was probably only constipation. When the family persisted, the doctor ordered blood tests, which revealed that Emily was anemic. The pediatrician then called in his colleague to perform a second examination, at which point both doctors recommended that the Wangs take Emily to the local emergency room at Maimonides Medical Center in Brooklyn for an ultrasound.
Emily was rushed to the ER for the ultrasound, which revealed that she had a large mass around her kidney. The ER doctor told the Wangs that the tumor was most likely Wilms' tumor, the most common cancer of the kidneys found in children. Emily was admitted to Maimonides that same day. “It was the most devastating day of our lives,” Tina says. “From the outset, Emily knew something was wrong. She just didn't know how to tell us.”
Two days later, deciding they wanted to send Emily to the best children's hospital in New York City, the Wangs transferred Emily to Children's Hospital of NewYork-Presbyterian/Columbia University Medical Center. A week later, Emily received a biopsy to determine if she did have Wilms' tumor. Two days after the procedure was performed, the doctors informed the Wangs that the mass was not Wilms' tumor but a rare cancer of the sympathetic nervous system known as neuroblastoma.
Afflicting only about 700 children in the US each year, neuroblastoma affects the nerve network that carries messages from the brain throughout the body. Some neuroblastomas will go away without any treatment, and others can be cured by surgery alone. But approximately half of all neuroblastomas have already spread to the bone and bone marrow by the time they are found and require more complex treatment.
“We were very disappointed and saddened because we were hoping the tumor was, in fact, a Wilms' tumor,” Tina offers. The overall five-year survival rate for children with Wilms' tumor is more than 90 percent. “We knew,” she continues, “that the outcome with neuroblastoma is not as positive.”
It was obvious to Emily that she was sick, Tina explains, but she also appeared to understand that the doctors would help her to get better.
Move to Memorial Sloan-Kettering
After doing some research, the Wangs scheduled an appointment at Memorial Sloan-Kettering Cancer Center. After meeting with the neuroblastoma team, led by Nai-Kong Cheung, the Wangs concluded that Memorial Sloan-Kettering had the most promising neuroblastoma treatment options, and they decided to transfer Emily from Children's Hospital.
Emily after the stem cell transplant
Because Emily's tumor was considered high risk, she was placed on what is called the N8 treatment protocol, which entails a combination of therapies: induction, surgery, radiation therapy, stem cell transplant, immunotherapy, and differentiation therapy. The initial phase of treatment, induction, consists of five rounds of chemotherapy. After the third round of induction chemotherapy, when the maximal reduction in tumor size had been achieved, pediatric surgeon Michael LaQuaglia operated to remove the primary tumor.
Emily then received a stem cell transplant, a procedure in which the patient's neuroblastoma-infected bone marrow is destroyed and then replaced with stem cells that are free of neuroblastoma. “Having Emily locked in a clean room for the monthlong period was difficult for all of us,” Tina says with understatement. “But she was a real trooper. Amazingly, she was able to entertain herself by having tea parties with her stuffed animals and watching her favorite videos. No matter how painful or hard it was for her, she would get herself out of bed every morning and enjoy her day as if she were a typical three-year-old.”
After that, in conjunction with radiation therapy and differentiation therapy using the drug Accutane® (generic name isotretinoin), Emily underwent numerous cycles of an immunotherapy that uses the monoclonal antibody known as 3F8. This treatment is designed to train the body's own immune system to detect and destroy neuroblastoma cells that have survived chemotherapy or radiation therapy.
“ I remember a doctor here at Memorial telling me, 'You'll see her getting very sick before you'll see her getting better.' This proved to be very realistic. “
Tina Wang, Emily’s Mother
Emily had a difficult time dealing with the side effects of chemotherapy. The treatment-induced nausea led to a loss of appetite, which in turn led to a dramatic loss of weight. “It was really tough at first,” Tina recalls. “Emily knew that she wasn't feeling well, but she didn't know why. She would cry when she saw the needles, and I would cry because I had to be the bad guy, holding her down. But she never saw me as the bad person. She would always want Mommy to be there to help her.” The 3F8 treatments proved especially painful because they also attack the neurosensory cells. Luckily, the treatments became more bearable as Emily received more of them. “Like many kids at Memorial, she learned to adjust to the pain,” Tina says in amazement.
Relapse and Investigational Treatment
Unfortunately, in March 2005, three days before completing the N8 protocol, a tumor was discovered in Emily's brain, signaling relapse. Surgery was performed immediately, with pediatric neurosurgeon Mark Souweidane removing the tumor. High-dose chemotherapy followed surgery, after which Emily started two rounds of 8H9 treatment. This is a promising new protocol that targets neuroblastoma cells in the central nervous system (CNS) using a monoclonal antibody known as 8H9. In this treatment protocol, a form of radioactive iodine is attached to the 8H9 antibodies. The antibodies can be safely injected into the cerebrospinal fluid, which bathes the CNS. The liquid radiation destroys neuroblastoma cells, which are targeted, without damaging normal cells.
In her research on neuroblastoma, Tina had heard that there were usually few options once the disease spreads to the brain. “I was devastated,” she says. “But Dr. Cheung was so calm and sure about the whole situation, telling us that there was this new treatment, 8H9, which could be used to bring Emily back into remission.”
“ We have a dream team here at Memorial Sloan-Kettering. As a result of this institution's efforts, we have come quite far, with many children surviving neuroblastoma.
Nai-Kong Cheung, Neuroblastoma Program Head
Emily had the distinction of being the first female patient to receive this protocol. Fortunately for Emily, the 8H9 treatments were both successful and much less painful than the 3F8 had been.
A Real Trooper…and a Healthy, Happy Child
Emily after treatment
Today, thanks to her resilience and successful treatment, Emily is a happy, strong, outgoing, and resilient little girl with a kind heart and an easy-going nature. Despite her treatment-related short stature and high-frequency hearing loss, she is very healthy and is doing well in school. Although she knows that she was once sick, she does not feel as if she is different from the other children around her in any way. “Emily is truly a very special and gifted child,” her mom marvels. “She kept our hopes up and taught us how special life really is. We learned that sometimes you can get the bad, but eventually the good comes around.”
Advising other parents of children recently diagnosed with neuroblastoma, Tina explains that they should prepare for a difficult and emotionally challenging journey. “I remember a doctor here at Memorial telling me, 'You'll see her getting very sick before you'll see her getting better.' This proved to be very realistic.”
Tina credits the neuroblastoma team at Memorial Sloan-Kettering with saving Emily's life. “We know that they spent countless hours in the laboratory developing revolutionary treatments like 3F8 and 8H9,” Tina emphasizes. “Prior to 8H9, there was no hope after relapse to the brain. We want to thank Memorial Sloan-Kettering Cancer Center and Dr. Cheung's team for their dedication to advancing neuroblastoma research. There is no better cancer treatment center, and I could not wish for a better hospital and medical staff for my daughter or anyone else's child.”