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Treatment Refinements Offer Global Benefits

By Keith Crabtree; Photo by Justin Veneman

When St. Jude oncologist Raul Ribeiro, MD, was a boy, he worked in a Brazilian pharmacy. His uncle Jair was a pharmacist.

Ribeiro rode his bike to make deliveries.

He understood the power of medicine to better people’s quality of life. But he couldn’t have known that one day he would advise hitting the brakes on the intensity of chemotherapy to save lives.

Ribeiro is committed to improving the care of children with acute lymphoblastic leukemia (ALL) by narrowing the gap in outcomes between high-income and low- to middle-income countries.

“When I came to St. Jude,” he says, “I compared the survival rates in the U.S. with other countries. I had this eye for disparity. I always thought, ‘How can we help decrease the gap?”

Indeed, high-intensity therapy boosted cure rates for ALL in developed countries, an upward trend that began decades ago.

“When we use intensive therapy in a region with limited resources, we see the opposite trend,” Ribeiro says. Children, for example, die of infection in low- and middle-income countries because the supportive care resources needed to manage complications from high-intensity regimens aren’t available.

Doctor addressing a group

A stand-over-the-crossbar moment

Years ago, oncologists in Recife, Brazil, stopped on the road and put the kickstand down to think about the route. More children with ALL than expected were dying early deaths. Could reduced-intensity therapy — similar to that used in high-income countries in the 1990s — make a difference in the cure rate? Could clinicians identify low-risk ALL patients who were likely to benefit from reduced-intensity therapy?

Boy on hospital bed smiling

Detecting minimal residual disease, or MRD, early in treatment with flow cytometric assay is key, but this technology can be complex and expensive. So, St. Jude developed a simple and inexpensive method.

Results of that study showed that lower-risk kids with B-cell ALL, the most common type of ALL, had excellent outcomes in response to low-intensity therapy.

The Recife protocol was used successfully for a clinical trial with many more participants at the Children’s Cancer Hospital of Egypt in Cairo. The results from Recife and Cairo point the way for physician-scientists in low- and middle-income countries to take advantage of the many benefits of risk-directed therapy, such as avoiding overtreatment, reducing toxicity, and decreasing the likelihood of long-term side effects.


The results from Recife and Cairo point the way for physician-scientists in low- and middle income countries to take advantage of the many benefits of risk directed therapy, such as avoiding overtreatment, reducing toxicity, and decreasing the likelihood of long-term side effects.


Pedaling faster

A national protocol in development in Brazil will follow the Recife procedures.

Ribeiro, who has cared for children from around the world for more than 30 years, makes a weekly call to the care team in Brazil to talk about cases. He says he has learned a few lessons along the way.

“You cannot simply transport a protocol from a developed country to a developing one and expect the results to be the same,” Ribeiro says. The disparity in supportive care, among other factors, will sabotage those efforts.

Having an eye for disparity and the ingenuity to find a different way of doing things can make the road to refined treatment for ALL less bumpy.


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