'Incredible' discovery
Chris Wong of the Jimmy Fund Clinic is on a pediatric treatment plan, which studies have shown is the best fit for patients under 21.
Each year, more than 1.4 million adults in the U.S. are diagnosed with cancer, versus 10,000 children. Leukemia represents about one-third of all childhood malignancies, but just 3 percent of adult cancers. In the case of acute lymphoblastic leukemia, or ALL, the number of patients who are over and under 18 each year is nearly equal. But when you put aside the number of individuals with the disease and look instead at their long-term prognosis, the same disturbing trends arise: For almost all forms of ALL, pediatric patients have a five-year survival rate without recurrence that is nearly twice that of their older counterparts.
In the late 1990s, two of my colleagues at the University of Chicago made an incredible discovery. Wendy Stock was a senior medical oncologist running a national clinical trial for adults with ALL; Jim Nachman was a pediatric oncologist and the principal investigator on a large, national pediatric trial of ALL. They found that because patients age 16-21 were eligible for either trial, they could study how outcomes differed depending on whether patients received an adult regimen or one designed for children. What they found fascinated them: While 64 percent of the patients on pediatric protocols were surviving disease-free for five years, just 38 percent of the same-aged "adults" were doing so.
Stock and Nachman presented their findings at the December 2000 meeting of the American Society of Hematology (ASH), and that was an eye opener for many of us in the audience. Over the next five years, we studied similar groups in the U.S., as did the French, Dutch, Brits, Swedes, and others. And if you look at the numbers, it's a reproducible trend.
It turned out that the difference that caused these disparities was in the delivery of treatment. A chemotherapy drug called asparaginase has long been standard use for ALL patients. Over time, it has become accepted in medical circles that adults age 18 and over cannot handle large amounts of this drug, because a small percentage of patients have developed pancreas inflammation and other complications. In children, however, asparaginase tolerance is expected and crucial. Patients treated at Children's Hospital Boston and most pediatric cancer centers in the United States have their bone marrow checked after 30 days of chemotherapy; if no visible leukemia cells are found, they receive their next dose of asparaginase within 1-2 days. The goal is to attack the residual bad cells that couldn't be seen, because the more cells that survive from one treatment to the next, the better chance they have of getting "smart" and developing resistance to the chemo.
If you're an adult being treated for ALL, or even a teenager put on the adult protocol, however, you have historically waited a week or so before your next doses of chemotherapy at some hospitals. This may mean that adults end up with more remaining leukemia cells after each cycle of treatment, which can result in a huge difference in cure rates nationally. We don't yet know, but at Dana-Farber we hope to find out.
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