Clinical trial results from St. Jude Children’s Research Hospital demonstrate the benefits of using genomics and early treatment response to guide risk classification of children with B-cell acute lymphoblastic leukemia (B-ALL). The study, published in Blood, indicates that certain genetic subtypes of B-ALL can be effectively treated with lower-intensity chemotherapy regimens, reducing the risk of side effects without compromising survival rates.
Enhanced Risk Assessment in B-ALL
Traditionally, the intensity of chemotherapy for B-ALL patients is determined by the National Cancer Institute (NCI) risk classification, which relies on clinical characteristics such as age and white blood cell count. However, researchers at St. Jude have refined these criteria by incorporating genetic subtypes and early treatment responses into risk assessments. The St. Jude Total Therapy XV and XVI clinical trials focused on two genetic subtypes of B-ALL: ETV6::RUNX1 and high-hyperdiploid.
According to Dr. Hiroto Inaba, St. Jude Department of Oncology, “In the St. Jude Total Therapy XV study, we began incorporating genetic information and response criteria into our risk assessment. This risk classification system allows us to identify patients who can be treated with lower-intensity therapies while ensuring that those who require more intensive treatment receive it.”
Positive Outcomes with Reduced-Intensity Treatment
The study evaluated outcomes of patients enrolled in the St. Jude Total Therapy XV and XVI clinical trials, correlating genomics- and early treatment response-guided risk assessment with patient outcomes. Results showed that 93% of patients with ETV6::RUNX1 and 54% of those with high-hyperdiploid B-ALL, who were traditionally considered high risk, achieved positive outcomes with low-intensity chemotherapy. These outcomes included excellent event-free survival rates.
Dr. Katelyn Purvis, St. Jude Department of Oncology, explained, “We now have tangible evidence that reduced therapy can be beneficial for some patients, which decreases toxicity. Our goal for every child who walks through our doors with leukemia is to not only cure them but also to extend their lives by decades with minimal side effects.”
Clinical Implications
The findings suggest that by using genome- and early treatment response-guided risk classification, clinicians can accurately identify patients who are likely to benefit from less intensive treatment. This approach reduces the incidence of side effects such as thrombosis and pancreatitis, which are often associated with high-risk therapy. The study supports a shift towards more individualized treatment plans in pediatric B-ALL, balancing the need for effective therapy with the goal of minimizing long-term health issues.
