The little girl screamed and shook her head, but the nurse was undeterred.
She intended to calm the child and access the port-a-cath, a device used to deliver life-saving chemotherapy. But first, she’d need the child to sit still.
Embarrassed, the mother pulled a toy from her bag, but her daughter pushed it away.
It was “dex” week.
Dex is dexamethasone, part of the treatment regimen for children with acute lymphoblastic leukemia (ALL), a cancer of the blood and bone marrow. Children receive this steroid and a chemotherapy drug called vincristine in intervals, called pulse therapy, during the second year of treatment.
What’s the quality of life for patients during that time?
“Not good,” says Ching-Hon Pui, MD, Oncology chair at St. Jude Children’s Research Hospital.
A standard of care since the 1970s, this dex-vincristine combo also has repercussions that extend far beyond the treatment phase. The problems include personality and mood disturbance; sleep problems; metabolic syndrome, which is linked to heart disease and Type 2 diabetes; and peripheral neuropathy, a type of nerve damage.
“The side effects from the dexamethasone and vincristine are not negligible,” says St. Jude oncologist Hiroto Inaba, MD, PhD, principal investigator of Total Therapy 17, a St. Jude clinical trial for ALL.
As a result, Pui — and an esteemed group of researchers in China — decided to look into the status quo and possibly change it.
In the U.S., the five year survival rate for childhood acute lymphoblastic leukemia is 90%. St. Jude takes steps to improve the outlook for children with that disease in China, Brazil, Egypt and beyond.
Collaboration is key
In the U.S., children with ALL have a survival rate of 90%. Yet, children in low- and middle-income countries, such as China, fare far worse.
In 2018, St. Jude Global embarked on a mission to change that scenario. A signed accord and research partnerships with China count among its many achievements.
Even before the global program began, Pui had been working for decades to improve outcomes for children with leukemia in China. Since 2006, he has spearheaded an annual teaching conference on childhood cancer in Asia. And, thanks to his efforts, ALL became the first childhood disease covered by the Chinese New Medical Insurance Policy—providing hope to thousands of underprivileged children in China.
Today, Pui serves as medical director of the St. Jude Global China Program. Under the hospital’s new strategic plan, Pui will continue to play an important role in improving treatment and research of front-line ALL studies in collaboration with the Chinese Children’s Cancer Group.
Lifting the burden
St. Jude children and families love Pui. He’s more than willing to do a magic trick or tell a good joke — or a joke good enough to elicit a groan — to make connections and quell treatment anxiety.
Understandably, some patients and families dread steroid pulses. Pui wondered if prolonged treatment with these drugs was necessary.
To find out, he collaborated with researchers in China to conduct a clinical trial with 6,108 patients — the largest randomized trial in pediatric leukemia history.
The scientists found that the dex-vincristine therapy could be safely eliminated in low-risk patients beyond the first year of treatment, effectively quashing toxic side effects linked to this regimen.
“Many parents will be very happy,” Pui says.
Additional studies will be needed to determine if this regimen can be omitted for patients in standard-risk groups.
“The weeks that they get this medicine are terrible,” Pui says. But the burden may be lifted for a substantial number of patients and families.
Ching-Hon Pui, MD, collaborated with researchers in China to conduct a clinical trial with 6,108 patients — the largest randomized trial in pediatric leukemia history.
Taking aim at relapses
Pui’s lifetime achievements in the fight against childhood leukemia are heroic, although he downplays his contribution.
His numerous projects act as stepping stones to cures and improved quality of life for children with this life-threatening disease.
In findings reported earlier this year, Pui also joined scientists in China to look at central nervous system or CNS relapse in ALL patients.
They found three factors contributed to a reduced risk of CNS relapse: treatment timing, the timing of dexamethasone treatment and the lumbar puncture for intrathecal (within the spine) therapy; total intravenous anesthesia, a type of sedation used during spinal taps; and flow cytometry analysis, a test for the presence of leukemic cells in the cerebrospinal fluid.
“We have a fruitful collaboration with the Chinese Children’s Cancer Group,” Pui says. “No single institution or even collaborative study group can enroll enough patients to conduct definitive randomized non-inferiority clinical trials, which requires thousands of patients to prove that treatment can be safely reduced, especially among those with low-risk leukemia. By working together, we achieve results that benefit children across the world.”
From Promise, Summer 2021