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Researchers at Children’s Hospital of Philadelphia Unveil Critical Factors for Survival after Relapse from Childhood Leukemia

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Researchers at Children’s Hospital of Philadelphia Unveil Critical Factors for Survival after Relapse from Childhood Leukemia

Researchers in the Children’s Oncology Group (COG) at Children’s Hospital of Philadelphia (CHOP) are highlighting key factors influencing survival rates after the first relapse of acute lymphoblastic leukemia (ALL) in children. The study, which is the largest of its kind to evaluate leukemia relapse in children, was published recently in the journal Leukemia.

September is Childhood Cancer Awareness Month, dedicated to recognizing children and families affected by pediatric cancer, and to raising awareness and support for research.

ALL is the most common form of leukemia found in children, accounting for approximately 30 percent of all pediatric cancers. In the United States, approximately 3,000 cases of ALL are diagnosed in children and youth up to age 21 each year. Despite an 85 to 90 percent cure rate after youth with ALL receive their first treatment, about 15 percent of children and adolescents with pediatric ALL will relapse. Some patients are unable to achieve remission because their cancer does not respond to treatment, a condition referred to as refractory leukemia.

Susan R. Rheingold, MD

“This study is significant because it greatly enhances our understanding of the complex factors that influence survival outcomes following relapse in pediatric patients with ALL,” said Susan R. Rheingold, MD, a lead author of the study, Institutional Principal Investigator for the Children’s Oncology Group and attending physician with the Cancer Center  at CHOP. “Our findings underscore the importance of prioritizing personalized medicine when treating ALL, as well as emphasizing the need for ongoing research to address gaps in therapy.” 

In this study, researchers analyzed data from patients enrolled in 12 COG frontline ALL trials between 1996 to 2014 to assess additional factors that are associated with overall survival post-relapse. Of more than 16,000 children evaluated, approximately 12.7% relapsed. Relapse rates were higher in infants (34.2%) compared with children with B-ALL (12.5%) or T-ALL (11.2%).

Researchers found the overall five-year survival rate after relapse was approximately 48.9%, with survival varying significantly based on factors such as type of leukemia, time to relapse, and site of relapse. B-ALL patients had a five-year survival rate of about 52.5%, while T-ALL patients had a lower survival rate of about 35.5%, and infants had the lowest at around 21.5%. 

Patients who relapsed later, after three years, had much better outcomes. For example, B-ALL patients who relapsed after three years had a survival rate of 66.4%, compared to just 25.8% for those who relapsed within 18 months. Similarly, T-ALL patients had a survival rate of 58% with a late relapse, compared to 29.8% for early relapse.

The site of relapse also impacted survival rates and varied depending on the patient's cytogenetic subtype, which refers to specific genetic characteristics of their leukemia cells. Certain genes contribute to relapse in specific areas, such as the bone marrow or central nervous system. 

Patients with the ETV6/RUNX1gene had higher post-relapse survival rates of around 74.4%, while those with the KMT2A gene had significantly lower survival rates of about 31.9%. 

Stephen P. Hunger, MD

“The fact that certain groups showed substantially higher survival rates is encouraging,” said Stephen P. Hunger, MD, a senior author of the study, and Chief of the Division of Oncology and Director of the Center for Childhood Cancer Research at CHOP. “Our findings offer hope and highlight the potential for more tailored and successful treatment strategies moving forward.”

This study was supported by funding from the National Cancer Institute of the National Institutes of Health grants and St Baldrick’s Foundation funding. 

Rheingold, S.R., Bhojwani, D., Ji, L. et al. “Determinants of survival after first relapse of acute lymphoblastic leukemia: a Children’s Oncology Group study.” Leukemia. Online September 11, 2024. DOI: 10.1038/s41375-024-02395-4.

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