Improved outcomes for the treating children with leukemia

Dr. Hiroto Inaba was raised in a rural province in Japan to honor his samurai heritage. His parents taught him the “Bushido” that an honorable life is one that upholds “the good fight,” Inaba says. After he lost his mother to cancer, he decided his fight would be as an oncologist tackling cancer.

In his 22 years at St. Jude Children’s Research Hospital, his work has involved improving the care and treatment for children with leukemia, specializing in two of the most common childhood cancers, acute lymphoblastic leukemia (ALL) and acute myeloid leukemia, (AML). 

“The good fight is to protect and to bring the best outcome for our patients and families,” said Inaba, MD, PhD, who joined St. Jude in 2003 and is now the director of the Pediatric Hematology Oncology Fellowship Program at St. Jude, mentoring the next generation of doctors caring for kids with cancer.

In the last 15 years, the work St. Jude has done through the Pediatric Cancer Genome Project (PCGP) has been particularly crucial for Inaba’s efforts to improve the diagnosis, treatment and survival for the children he treats. 

The PCGP is a groundbreaking collaboration between St. Jude and the Washington University School of Medicine. The primary goal of the project, launched in 2010, was to identify and learn the genetic causes of childhood cancer. 

Genomic data from the project has helped doctors like Inaba develop tailored therapies that attack specific abnormalities found in cancer cells, allowing treatments to be more effective with fewer side effects. The project has also allowed researchers and doctors to identify genetic mutations to understand what variations in the DNA cause pediatric cancers to start, grow, become resistant to treatment and even return.

Sequencing the genome for children with cancer has also led doctors to more accurately diagnose and stratify risks of the disease. Better diagnosis and risk stratification have meant more personalized care for each child with cancer and improves overall outcomes, a key step toward raising survival in high-risk leukemia and hard-to-treat brain tumors.

“In many regards, the PCGP came into being because of the need to accelerate progress,” said St. Jude President and CEO James R. Downing, MD. “It succeeded because we were willing to chase big ideas and make the most of a unique moment in history.”

Genomic sequencing of ALL has improved understanding of the disease which now has a 94 percent survival rate. 

“We can cure most of the patients with this disease. But still, as a physician, we really need 100 percent; six percent we (still) need to cure,” Inaba said. “So, we are working on many new technologies and treatments to improve this.”

The PCGP allowed the discovery of previously unknown subtypes of ALL, so doctors are able to further personalize medicine, adjusting chemotherapy based on the molecular and genetic analysis of the tumor cell.

In Inaba’s clinic, discoveries and learnings from the PCGP have informed a key clinical trial, TOTAL 17, for newly diagnosed patients with ALL and acute lymphoblastic lymphoma (LLy). 

This clinical trial used precision medicine strategies based on the inherited and acquired leukemia-specific genomic features. Researchers want to see if the targeted treatment approaches improve the cure rate and quality of life of children with ALL and LLy. 

The active trial has 790 participants, spread across 8 locations (7 in the U.S. and 1 in Australia). Enrolling so many in the study allows researchers to gather large amounts of data more quickly. This research is made possible by the breakthroughs of PCGP that made identifying genetic alterations of importance in ALL feasible. The PCGP has also identified numerous biomarkers that can be used for early diagnosis, risk stratification and monitoring treatment response in pediatric cancer patients.

Over the last 15 years, Inaba said he has been excited to see research in molecular analysis, immunotherapy and genome sequencing conducted in St. Jude laboratories translating into better diagnosis and treatment for patients in clinics. He calls the discoveries “amazing,” even as he admits work remains until St. Jude is able to carry out its founder’s promise that “no child should die in the dawn of life.”

Inaba said he would also like to see more progress made in the treatment and survival of kids with acute myeloid leukemia (AML). The PCGP has helped doctors like him understand how heterogenous the disease is, making it difficult to treat, because it can affect each child so differently. Eventually, he said, he hopes doctors are able to create individualized therapy for each child with AML. In the 1980s, survival for children with AML was 30%, Inaba said. Today, it is about 70%.

“Significantly, survival is improving, still we have 25 to 30 percent of patients to save,” Inaba said. “In this field, there is new therapy coming such as molecular targeted therapy and also immunotherapies under research now, so I hope AML will also come to the level of acute lymphoblastic leukemia (ALL).”