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Improving Treatment Protocols
New Study Presented at ASH Reveals Improved Outcomes in DS-ALL Patients

"Having an abstract accepted for presentation at the annual ASH meeting, especially oral, is a real honor."

In an exciting turn of events, CHRCO clinical scientist Caroline Hastings, MD, is presenting the results of a new study at the annual meeting of the American Society of Hematology (ASH) in early December.

“The ASH is the largest hematoloby association both for clinical and basic research in United States, probably in the world," says James Feusner, MD, director of the CHRCO oncology department.

The results are based on just-concluding research conducted with Dr. Hastings and her colleagues on improved outcomes in children with both Down syndrome (DS) and high risk acute lymphocytic leukemia (HR-ALL).

While DS only occurs in about 2 to 3 percent of children with ALL, it is a big area of study.

"This is because children with DS have a nearly 10 to 20 fold increased risk of developing ALL," explains Dr. Feusner. "Researchers guess that it has something to do with the fact that they have extra genetic material that must have something to do with that increased risk."

In addition to increased risks, once children with DS develop ALL, they also face increased sensitivity to standard treatment protocols. For this reason, DS-ALL patients have in general been treated less aggressively. In the latest study presented at the annual ASH meeting, however, DS-ALL patients participated in a randomized treatment that did not modify the treatment protocols for patients with DS - with results both surprising and encouraging.

"While it's been known that DS patients have increased sensitivity to side effects of certain meds, there was no adjustment in this protocol - yet the children in this study with DS had the same survival rate as children without DS with exactly the same treatment. That was the surprise."
Given the increased sensitivity, one would have expected instead that the overall survival rate would have been less for DS patients, due to toxicity and related complications. When the comparisons were broken down by a variety of statistical endpoints, however, they results still held up.

"The first comparison has to do with event-free survival," explains Dr. Feusner. "This takes into account death or relapse or second malignancy, and there was absolute no difference between the DS-ALL kids and the ALL kids - the curves were super-imposable 5 years out from treatment, not even a hint that there's a difference that way."

The expected deaths due to toxicity were nowhere in evidence when looking at event-free survival rates. In addition, DS-ALL patients responded similarly well as ALL patients to a boost in therapy that was geared to addressing a long-known issues for patients who have slow remissions. In fact, the only comparison in which DS patients showed the effects of increased sensitivity was when death as a first event was analyzed.

"Here there was a difference," says Dr. Feusner. "It wasn't huge, but because of the small number of patients in the study, it was statistically significant, with 5 percent of non-DS patients dying as a first event, compared to 12 percent of DS patients."

As Dr. Hastings is reporting to the ASH, however, this isn't entirely bad when compared with the overall event-free outcome.

"That these DS patients had the same event-free survival as non-DS patients indicates that the control of the leukemia was actually a little better," says Dr. Feusner. "They may have had more deaths from toxicity than non-DS patients, but they had fewer deaths from relapse."

This means that the new study not only suggests treating DS-ALL patients just as aggressively as ALL patients as a norm, but it also implies that the results could be even better.

"In general, the approach taken here to DS patients in the high-risk ALL group is justified," says Dr. Feusner. "But treatment can be improved even further by coming up with better supportive care to prevent the deaths in patients who are in remission."

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Monday, May 16, 2011 11:33 PM

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