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by Elizabeth Jane Walker
St. Jude boosts cure rates for older teens with acute lymphoblastic leukemia.
West Rountree’s friends hugged and high-fived one another, tilting purple mortarboards at rakish angles and snapping photos with cell phones. As he filed into the auditorium with his 260 classmates, West fought against nausea and a bone-deep exhaustion. How, he wondered, would he be able to endure his high school commencement exercises?
“I walked across the stage, and before the ceremony was over, I went home,” West recalls. During a graduation cookout that evening, he slipped away from his well-wishers and collapsed into bed, burning with fever. When his condition persisted the following day, his family took him to the hospital. To their shock, a bone marrow test revealed acute lymphoblastic leukemia (ALL).
“I didn’t know much about leukemia,” West says. “I thought little kids and old people got it. I didn’t know that people my age got it.”
While West’s friends packed their suitcases for a senior trip to Florida, the new graduate embarked on a different kind of journey. Within hours of his diagnosis, West boarded a plane bound for St. Jude Children’s Research Hospital in Memphis, Tennessee.
For nearly 50 years, St. Jude researchers have been seeking a cure for ALL. Each study has built on the success of preceding protocols—refining, tweaking, moving treatment outcomes inexorably higher. In spite of that progress, ALL cure rates for older teens have been disproportionally lower than those for younger children. A dozen years ago, teens like West had only a 59 percent chance for a cure, compared with an 88 percent rate for children ages 1 through 14.
Because of individualized treatment and supportive care, those numbers have skyrocketed. In a recent report in the Journal of Clinical Oncology, St. Jude investigators announced a nearly 30 percent increase in the survival rate for ALL patients who were 15 to 18 years old when their cancer was found. The five-year overall survival rates were 88 percent for those teens and 94 percent for younger children. The patients’ quality of life increased as well, thanks to the elimination or reduction of drugs that cause such long-term side effects as infertility and second cancers. The St. Jude study, called Total XV, also eliminated cranial irradiation, which had traditionally been used to prevent central nervous system relapse. Radiation to the brain can cause problems with attention, behavior and learning. Investigators were thrilled to discover that radiation could be removed without affecting cure rates.
Ching-Hon Pui, MD, St. Jude Oncology chair, cites several reasons that teens have traditionally had lower ALL survival rates than younger children. Older teens are more likely to have high-risk subtypes of the disease, to experience more side effects from treatment, and to have cancer cells that are resistant to chemotherapy drugs.
“Another reason is treatment adherence,” Pui observes. “When the kids are young, their parents make sure that they take their medicines. But teens may not be compliant with the treatment. They may decide they don’t want to risk being nauseated if, for example, they have a party the next day. So they won’t take their medicine. Also, when ALL is in remission, the teens begin to feel good; they think they’re cured, and they stop taking their medicine.”
The past year has been extremely challenging for West.
“My third methotrexate high-dose treatment was the hardest part thus far,” he says. “I had super nausea and other problems. I couldn’t eat for five days.”
Pui says that teens like West often experience severe side effects from treatment.
“Almost every toxicity is more common in older teenagers,” Pui says. “In general, they do not tolerate chemotherapy very well. They have more side effects from the same treatment we give to younger children.”
The reason behind the toxicity is that teenagers process drugs in a different way than younger children do.
“When you give a dose of a medication to an older child, their blood levels of that drug are actually higher than they are in younger children who get the same dose of the drug,” explains Mary Relling, PharmD, Pharmaceutical Sciences chair. “So we’re walking a tightrope. On the one hand, if we give teens more medications, they’ll have more side effects and more toxicity. On the other hand, if we give them less of the anti-cancer drugs, they might be at a higher risk for relapse because their leukemia cells are more resistant to the anti-cancer drugs.”
In Total XV, St. Jude clinicians introduced several elements that destroyed leukemic cells yet minimized side effects.
“We used a combination of genetic testing and pharmacologic testing,” Relling says. “For every single child, we individualized the amount of methotrexate to reach a specific target plasma level.”
Dosages of other drugs were adjusted, as well, based on risk status. Following the initial phase of treatment, clinicians evaluated the minimal residual disease, or MRD, status of each patient to decide how to further individualize therapy. Pioneered at St. Jude, the MRD screening technique can detect even one malignant cell among 100,000 normal cells. The test allows clinicians to evaluate how well a child has responded to therapy and to predict the risk of relapse. St. Jude is the first institution to use MRD to guide therapy for front-line leukemia protocols. If a child has residual leukemia at the end of remission induction therapy, the disease is reclassified as higher-risk and a more intensive course of treatment is given.
Patients with ALL must take multiple drugs by mouth for three years. Teens offer many reasons for skipping their oral medications. They may honestly forget. They may hope to minimize nausea or hair loss. They may believe that they can forego their medicine if they are feeling better. Or they may just be going through a rebellious phase.
Pui, Relling and their colleagues have heard all of the excuses. Nevertheless, they know that treatment adherence is crucial. To ensure that teens receive optimum treatment, the investigators require regular intravenous administration of drugs. Patients also receive chemotherapy directly into the spinal canal, so that the drug can penetrate the blood-brain barrier. Clinicians counsel with the teens, encouraging them to take their oral medications regularly.
“We pay close attention to treatment adherence,” Pui says. “We give at least one drug intravenously each week and we monitor the blood levels of drugs regularly so that we can identify patients who are not taking the oral medications. If the levels aren’t high enough, we sit down with the patient and talk about improving compliance. The next time we check, we’ll find out that they are taking the medicine.”
Even though West towers over most St. Jude patients—and many staff members—the tall, lanky teen is enrolled in a pediatric treatment plan. Research has shown that survival rates are better for teens who are treated on pediatric rather than adult protocols. That success may be due to the more intensive therapy and the higher emphasis on treatment adherence.
“There has been controversy in the past over the best way to treat adolescents with ALL,” Relling says. “Should they be treated on pediatric treatment protocols or on adult treatment protocols? Our findings further cement the conclusion that these children really should be treated on pediatric treatment protocols.”
Teen patients have a set of unique needs when compared to young children or adults. At St. Jude, clinicians and researchers unite to identify and address those needs.
“We have a dedicated team for each type of cancer,” Pui says. “Everybody at St. Jude specializes in a specific type of cancer—from the social worker to the doctors, dietitians, pharmacists, nurse practitioners, nurses and physical therapists. We individualize our therapy based on pharmacokinetics, pharmacogenetics and pharmacodynamics. That cannot easily be done by any institution. It has to be done by an institution as sophisticated as St. Jude.”
The results speak for themselves.
“We were pleased to find that close to 90 percent of older adolescents can be cured with chemotherapy without the need for bone marrow transplantation,” Pui says. “Importantly, not only do we have the highest cure rate, but our patients survive with good quality of life because they don’t get any radiation.”
West Rountree still has a long way to go before he completes his leukemia treatment. He eagerly anticipates the day that he can resume his life: Go on a vacation to replace the senior trip he missed; dust off his skateboard and try out a few moves; hang out with his friends; jump-start his future. “When I get finished with this, I’m going to college,” he says. “I’m still trying to decide what I want to be.”
Promise magazine, Spring 2011