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by Elizabeth Jane Walker
The tiniest patients face the biggest odds when it comes to acute lymphoblastic leukemia. St. Jude clinicians and researchers work to change that scenario.
Four-year-old Camille Davis has a precocious way with words. On this day, before scampering off to play with her three sisters, she approaches her mother, Lois.
“Mama, I’m going to give you a hug because you are so cute today,” says Camille, extending her arms for a breezy embrace.
Lois smiles when she reflects on how far her daughter has come. A little more than three years ago, doctors discovered that Camille had the most aggressive type of childhood leukemia and an extremely poor survival rate. A couple of years later, the toddler also experienced a dangerous cardiac problem that required open-heart surgery.
Although those events were incredibly stressful, Lois admits that one of the most difficult tasks she faced was closing her Internet browser and placing her trust in the scientists and clinicians at St. Jude Children’s Research Hospital.
“When we arrived at St. Jude, I started reading everything I could, whether it was from the Internet or from the library at the hospital,” Lois says. “That’s when I started getting scared and crying a lot. I thought, ‘If Camille only has a 20 percent chance to live, what are we even doing here?’”
Camille’s treatment team encouraged Lois to quit pondering the bleak survival rates for infants with acute lymphoblastic leukemia (ALL); instead, they suggested that she approach the challenges one day at a time.
“Soon I noticed that every week, Camille was getting a little bit better,” Lois says.
The journey had begun with a small bump on the head of the 7-month-old.
“Just keep an eye on it,” a pediatrician told Lois and Casey Davis. A week later, dozens of nodules appeared on Camille’s scalp. MRIs, CT scans and blood work failed to produce a definitive diagnosis.
“First they said it was a brain tumor; then they said she had tumors in her belly; then they said it was lymphoma,” Lois recalls.
Camille’s physician arranged for the couple to take their baby to St. Jude.
“We arrived at 1:30 a.m., and they immediately started doing tests,” Lois recalls. “Within 24 hours, we knew exactly what Camille had, and she had already begun receiving chemotherapy.”
The Davises learned that their daughter had ALL. Although most children with that disease have a projected cure rate of 90 percent, the outlook is not rosy for the 3 percent of ALL patients who are infants. About 80 percent of those babies have an MLL gene rearrangement, which has a dismal outcome.
Camille had the MLL rearrangement. Her disease affected the central nervous system, which further increased her risk of treatment failure. Scans indicated that in addition to the bumps on her scalp, Camille had lesions that extended deep into her brain. Her spinal fluid also contained leukemic blasts.
In another cancer center, Camille would have received radiation to her brain, a treatment that would have affected her ability to learn and develop normally. But radiation was removed from ALL therapy at St. Jude when oncologist Ching-Hon Pui, MD, and his colleagues made an important research discovery. They reported that children who receive highly personalized chemotherapy treatments actually enjoy better survival and quality of life than do children who receive a combination of chemotherapy and cranial irradiation.
Camille directly benefited from that discovery.
As part of the hospital’s Total XVI protocol, Camille received an intensive chemotherapy regimen. Some drugs were administered orally or through her central venous catheter, while others were injected directly into her cerebrospinal fluid. Infants with the MLL rearrangement in the Total XVI study receive a novel combination of medications, including clofarabine, a drug that was developed for pediatrics by St. Jude investigators.
Oncologist Sima Jeha, MD, worked closely with clinical pharmacists and other members of the treatment team to ensure that Camille received the optimum doses of drugs.
“Camille needed the highest doses of chemotherapy she could tolerate to clear her disease, but not so much that it would cause unacceptable toxicity,” Jeha says. “You have to have a balance. We are fortunate to have the greatest pharmaceutical service in the world and to be one of the first centers to integrate pharmaceutical science into therapy.”
During a visit home in April of 2010, Camille developed fluid around her heart. She and her mom quickly boarded a plane and returned to St. Jude. Soon after their arrival, Lois, pregnant with her fourth child, was shocked to feel the first pangs of premature labor.
St. Jude nurses took care of Camille while Lois rushed to a local maternity ward. As Lois delivered a baby across town, Camille began to have trouble breathing and her blood pressure skyrocketed. She was admitted to the St. Jude Intensive Care Unit.
The day after delivering her fourth daughter, Lois returned to St. Jude. There, she witnessed Camille going into cardiac arrest.
“They administered CPR and put Camille on the ventilator. It seemed like a bad dream,” Lois says.
Cardiologists discovered that the toddler had a heart aneurysm as well as a viral infection.
“Camille needed open-heart surgery,” Jeha recalls. “As her treating physician, I had the support of experts in infectious diseases, cardiology, cardiovascular surgery and intensive care. We all worked together to decide how to time the interventions, how long to safely hold chemotherapy, and other issues regarding the management of such a high-risk child.”
Thanks to exceptional teamwork and superior supportive care, Camille recovered from her surgery and completed her chemotherapy in December of 2010. Her disease remains in remission.
Although Camille has responded well to therapy, the prognosis for babies with ALL remains grim. Infant ALL survival rates have not kept pace with the increases experienced by some other forms of childhood cancer.
“We’ve figured out that we can get comparative results without radiation, which is a big, big step. But it’s still a bad disease,” says James Downing, MD, St. Jude scientific director, deputy director and executive vice president. “We need fundamental knowledge on the genetic lesions that underlie this leukemia before we can substantially improve the outlook for these patients.”
At St. Jude, efforts are underway to better understand the origins of infant ALL and to develop effective ways to prevent and treat it. The hospital recently recruited a new faculty member who will study the disease in the clinic as well as in the lab.
Through the Pediatric Cancer Genome Project (PCGP), St. Jude and Washington University School of Medicine in St. Louis are collaborating to learn more about infant ALL. Investigators are sequencing the entire genome of the leukemia cells to define the total complement of mutations that drive the formation of this form of leukemia. From information gained from the project, scientists and clinicians hope to develop therapies that will substantially improve the cure rate for infant ALL.
“We chose to include infant ALL in the PCGP because it has an abysmal cure rate,” Downing explains. “We want to know if there are no mutations, very few mutations or key recurrent mutations that underlie infant ALL. We’ve completed sequencing 22 cases thus far. Our team of scientists are working around the clock analyzing the data.”
Lois is thankful for the scientists and clinicians who are dedicated to learning more about infant ALL. In addition to assuaging her fears about Camille’s health, St. Jude staff helped alleviate Lois’ worries about health care costs. “There is no possible way with all the help in the world that we could have been able to afford all that St. Jude gave her,” Lois says.
Now, with the terrors of infant ALL behind them, Lois and Casey revel in their active, healthy—and messy—little girls.
“Mama, I cleaned my entire room all by myself. Are you so proud of me?” Camille asks, her blue eyes shining.
Promise magazine, Autumn 2011