Cross-border ‘twinning programs’ may reduce survival disparities for childhood leukemia

CHICAGO — A few miles can mean a life or death difference to children with cancer, if those miles cross a national border. “Twinning programs” helped to reduce survival disparities in childhood acute leukemia between high-income and lower-income countries, according to a study presented here at the American Society of Clinical Oncology on Saturday.

In 2008, researchers and clinicians at Rady Children’s Hospital, the University of California, San Diego, and Hospital General-Tijuana created one of these twinning programs, where two “sister hospitals” share training, expertise, research, and other resources for the mutual benefit of patients in both countries.

Pediatric acute lymphoblastic leukemia is the most common childhood cancer and, for the most part, it’s curable — if you live in a high-income country and have access to pediatric cancer experts. More than 80% of children with ALL treated at Rady Children’s survive their cancer. But just 20 miles away, over the U.S.-Mexico border, children treated in Tijuana had far worse chances. Globally, overall survival for pediatric ALL in low-middle income countries ranges from 10% to 60%.

“The disparities are huge,” said Paula Aristizabal, the lead researcher on the study and a hematologist-oncologist at Rady Children’s and UCSD. “Twenty miles away is like a world away. What really motivated us was seeing the team in Tijuana really doing everything they can for their patients, but they didn’t have the resources we have here in the U.S.”

Back in 2008, before Aristizabal and her colleagues started the twinning program, Hospital General-Tijuana didn’t have a pediatric oncology service, reliable access to key chemotherapies, or trained pediatric oncology nurses and doctors. When children came in with cancer, “they were treated by an adult physician, not a pediatric oncologist,” Aristizabal said. “They also didn’t have access to supportive care or comprehensive interdisciplinary teams including psychologists, dietitians, infectious disease specialists, intensive care physicians trained in complications with pediatric cancer. Our goal was to help them develop all of these.”

The program didn’t just provide training to hospital staff, Aristizabal said, but also tried to solve any other issues that patients encountered, including transportation, housing, and long-term access to medicines. In that sense, she said, the program took a holistic approach toward strengthening the health system in Tijuana. The team sought and received funds from the Mexican government for some medicines.

“That was really a struggle, not having access to medications,” she said. “We partnered with a small local foundation that we helped grow over the years. They helped support medications that the government does not provide, and we were able to grow infrastructure.”

After four years, the team began analyzing results, comparing overall survival from 2008 to 2012 against survival in 2013 to 2017. In a paper published on Saturday in JCO Global Oncology, the team reported that the survival for standard-risk ALL in Tijuana went from 73% before 2012 to 100% in the later period. Survival for children with high-risk ALL went from 48% to 55%. The overall survival for all children with ALL, including both average- and high-risk cancers, went from 59% to 65%.

“I think they did a tremendous effort to carry out this type of program,” said Roberto Rivera-Luna, a pediatric oncologist and hematologist oncologist at the National Institute of Pediatrics in Mexico City who did not work on the study.

At the same time, Rivera-Luna added, survival for pediatric ALL had also been on the rise during the study period. An analysis done about five years ago of 60 hospitals nationwide in Mexico, including Hospital General-Tijuana, showed that the national average for survival was around 62%, he said. That makes it difficult to tease out how much the program alone improved survival in Tijuana, and how much was due to a general national trend of improvement. Even so, he said the program created training opportunities that surely did help improve care in Tijuana.

But before the study period, survival for pediatric ALL was only 10% in Tijuana, Aristizabal said. “The twinning program started in 2008 and during the first years, it quickly increased to 59%,” she said. Then, it continued to increase to 65%. Those changes were not observed in a different study done across Mexico from 2005 to 2017. “These improvements are remarkable and, across Mexico, survival did not improve in 10 years, whereas in our program, survival kept improving with time.”

Rivera-Luna noted that survival rates in Mexico — and Tijuana in particular — still lag behind the high cure rates in high-income countries for pediatric ALL. That might be due to a multitude of factors, including an ongoing need for full-time pediatric oncologists and nurses and a lack of adequate research on ALL in children of Mexican descent. “Both Mexican children and Mexican American children may have different genomic factors that influence the results,” Rivera-Luna said.

That might mean that children of European descent and children of Mexican descent might fare differently as a population when treated with the same protocols. In the U.S., research suggests that children of Latino descent tend to get ALL more often and have worse outcomes than white children. Rivera-Luna’s institution has a twinning program with St. Jude Children’s Research Hospital, follows the same protocols, and has ample staff and resources, but even its survival rate of 78% isn’t on par with that of St. Jude’s.

“In this case, it’s not poverty. It’s not ignorance on our side. It’s a matter that goes well beyond a routine care of these children,” Rivera-Luna said. “We must go deeper into the biology of Mexican children.”

On that note, Rivera-Luna said the twinning programs provide “an excellent opportunity to research and increase knowledge of childhood cancers.” That research could ultimately help scientists better understand what influential cancer mutations are more common in ALL among children of Latino or Mexican descent and improve the care of all children who carry such mutations.

These programs may also have lessons for improving care in the U.S. that have poor access to pediatric cancer centers, said Gwen Nichols, chief medical officer of the Leukemia and Lymphoma Society, who did not work on the study. “There’s no pediatric centers in many of the mountain west states. If your kid gets cancer in Wyoming, you gotta go to Utah or Colorado or Mayo in Minnesota,” she said. “But here, there’s really nice evidence that providing the right protocols, training, staff, and more, we could do this in more places and improve outcomes without developing a new drug.”

The twinning program between San Diego and Tijuana has already yielded information that’s helped improve care for both hospitals, said Rady’s Aristizabal. “It’s a collaboration,” she said. “It’s not like U.S. doctors telling them how to do things, and we’ve learned a lot, too.” In particular, she said, the partnership has helped doctors in San Diego improve their cultural competency in treating Hispanic patients. “Fifty percent of our patients in San Diego are Hispanic,” She said. “So, that’s been huge for us at the border region.”