St. Jude clinicians announce the best survival rates ever reported for ALL. What could be better than that? Achieving those rates without the use of cranial irradiation.

As part of his job as a neonatologist, Venkat Kakkilaya, MD, sometimes has to share bad news with families. It’s never a pleasant experience. But he recently encountered a much more daunting task: informing his wife, Hema, that their son had acute lymphoblastic leukemia (ALL), a cancer of the white blood cells.

“Telling Hema was not easy,” he recalls. “It was a very traumatic day. The worst day in my life, I would say.”

But when the family arrived at St. Jude Children’s Research Hospital, Oncology Chair Ching-Hon Pui, MD, shared some encouraging news. Eleven-year-old Akash would receive a carefully personalized chemotherapy regimen to combat his disease. And—unlike countless children who have been treated for ALL in the past and many being treated to date worldwide—Akash would not have to undergo cranial irradiation as part of that therapy.

Earlier this year, Pui and his St. Jude colleagues established that children who receive personalized chemotherapy treatments actually enjoy better outcomes than children who receive a combination of chemotherapy and cranial irradiation. In the New England Journal of Medicine, the researchers announced that they had achieved the highest cure rates ever for ALL.

“This is the first study that proves that with effective chemotherapy, cranial irradiation can be totally omitted in all children with ALL,” says Pui, an American Cancer Society professor.

Akash Kakkilaya is one of many children who are reaping the benefits of that research.

Early triumphs

To understand implications of this study, rewind to 1962—the year the Beatles released their first hit, John Glenn orbited Earth and St. Jude opened its doors. The outlook for children with ALL was grim; 96 percent would not survive their disease. Chemotherapy for ALL was in its infancy. Remissions—when they occurred—were typically brief.

St. Jude clinicians soon noticed that many of the children who achieved remission died after cancer cells reappeared in the fluid surrounding their brains and spinal cords. When St. Jude began administering preventive radiation to the cranium and spine, the cure rate jumped to 50 percent.

“This was one of the biggest single gains in anti-tumor effectiveness that has ever been seen,” observes Mary Relling, PharmD, St. Jude Pharmaceutical Sciences chair.

For a while, nearly every child with leukemia received radiation to the brain and spinal column. But the side effects were harsh: learning deficits, hormone imbalances and a high risk of second cancers.

Since the 1970s, clinicians have sought to reduce the amount of radiation necessary to achieve cures. In recent years, many institutions have used cranial irradiation only on children who demonstrated the highest risk of central nervous system (CNS) relapse. According to Pui, about 20 percent of patients with high-risk leukemia currently receive preventive cranial irradiation each year in other U.S. institutions. In some developing countries, clinicians continue to use radiation treatments for most children with ALL.

“It has been a judgment call among different centers about whether they are willing to put up with the increased risk of late side effects in order to have a higher antileukemic effect,” Relling says. “Obviously we think that it’s not worth the risks.”

To individuals who question whether St. Jude is correct in removing radiation from ALL treatment, Pui’s answer is succinct: “No patients have died of CNS relapse in the past decade at our center.”

A new look at old drugs

To obtain the latest survival rates, the researchers designed a protocol featuring drugs that have been a part of the ALL treatment arsenal for years.

“There haven’t been that many new drugs for ALL introduced in the past few decades, but our ability to select and dose the ones we currently have has improved tremendously,” explains William E. Evans, PharmD, St. Jude director and CEO.

The new study used 11 anticancer drugs. Some medicines were infused directly into the spinal cord, while others were administered into the bloodstream. Investigators tailored treatment based on each child’s genetic make-up and how that patient metabolized, absorbed, excreted and responded to the drugs.

Investigators modified therapy based on a test performed in the lab of Dario Campana, MD, PhD, Oncology. The minimal residual disease or MRD test detects even the smallest number of leukemia cells that remain after the first six weeks of chemotherapy.

“Parts of this regimen have been used by other groups, but it has never been used in exactly this cocktail,” Relling says.

Sharing the good news

Children in the St. Jude study enjoyed a five-year survival rate of 94 percent and a projected 10-year cure rate of 90 percent. Plus, their quality of life should be better because of the absence of radiation treatments. Indeed, early neuro-psychologic testing showed that survivors of the study have normal intelligence as compared to the normal population.

“The five-year survival rate in the U.S. and in Western Europe (with the use of radiation) is approximately 85 to 90 percent,” Pui explains. “The rates in other parts of the world are lower.”

Is it possible for other cancer centers to replicate these results? St. Jude researchers respond with an enthusiastic “yes.”

“Now that we have shown that it works, anybody at a major academic medical center should be able to implement this,” Evans says. “Of course, that’s what St. Jude does—we focus on research and then share it with the intent of impacting the care of kids who never come on our campus. When we are pushing the cure rates this high, that’s terrific news for families.”

It’s also terrific news for Akash Kakkilaya, who does not have to worry about the learning deficits caused by cranial irradiation. Instead, this sixth grader who excels in science and math anticipates the day when he can return home to participate in all of his regular activities—cured of ALL.

Reprinted from Promise Autumn 2009

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