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Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is a form of leukemia, or cancer of the white blood cells characterized by excess lymphoblasts.

Malignant, immature white blood cells continuously multiply and are overproduced in the bone marrow. ALL causes damage and death by crowding out normal cells in the bone marrow, and by spreading (infiltrating) to other organs. ALL is most common in childhood with a peak incidence at 2–5 years of age, and another peak in old age. The overall cure rate in children is about 80%, and about 45%-60% of adults have long-term disease-free survival.

Acute refers to the relatively short time course of the disease (being fatal in as little as a few weeks if left untreated) to differentiate it from the very different disease of chronic lymphocytic leukemia, which has a potential time course of many years. It is interchangeably referred to as Lymphocytic or Lymphoblastic. This refers to the cells that are involved, which if they were normal would be referred to as lymphocytes but are seen in this disease in a relatively immature (also termed 'blast') state.

New Approach To B-ALL Treatment Reduces Side Effects And Enhances Survival

Clinical trial results from St. Jude Children's Research Hospital demonstrate benefits to using genomics and early treatment response to guide risk classification of children with B-cell acute lymphoblastic leukemia (B-ALL). Traditionally, the intensity of a patient's chemotherapy regime is guided by the National Cancer Institute (NCI) risk classification, which is largely determined by clinical characteristics such as age and white blood cell count at presentation. Through the flagship St. Jude Total Therapy clinical trials, investigators looked at two genetic subtypes of B-ALL (ETV6::RUNX1 and high-hyperdiploid). 

Results showed that patients with ETV6::RUNX1 and high-hyperdiploid B-ALL who, by NCI risk assessment would have received a high-intensity treatment regimen, could complete a low-intensity regimen and achieve positive outcomes.These findings were published today in Blood.

An enhanced criteria for risk assessment 

Risk-based chemotherapy is a tailored approach that adjusts the intensity of treatment based on the individual patient's risk factors, and its implementation has improved cancer care outcomes. However, traditional risk factors by NCI criteria do not provide a complete picture of prognosis. Modern studies, including the recent St. Jude Total Therapy clinical trials, have refined these criteria by incorporating genetic subtypes and early treatment responses into assessments. 

Patients with ETV6::RUNX1 and high-hyperdiploid B-ALL make up 25% and 30% of B-ALL cases, respectively. These patients can be classified as low risk provided they have no central nervous system or testicular involvement and respond well to induction (initial) chemotherapy. This approach reflects a shift towards a more individualized risk assessment model, accounting for both genetic and clinical factors to better tailor treatment plans.

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."

Hiroto Inaba, MD, PhD, corresponding author, St. Jude Department of Oncology

"We strive to be mindful of using only the necessary treatments to achieve a cure, aiming to minimize the risk of enduring health issues and side effects from a child's cancer treatment," explained first author Katelyn Purvis, MD, St. Jude Department of Oncology.

Reduced-intensity treatments yield positive outcomes

In this study, researchers evaluated patient outcomes from those enrolled on the St. Jude Total Therapy XV and XVI clinical trials. They looked at the correlation between genomics- and early treatment response-guided risk assessment and patient outcomes. By treating 93% of patients with ETV6::RUNX1 and 54% of those with hyperdiploid B-ALL who were traditionally considered high risk with low intensity chemotherapy, the investigators were able to achieve positive outcomes including excellent event-free survival rates. 

"We tailored chemotherapy to better match patient needs and successfully identified who could benefit from low-intensity therapy. This strategy highlights our goal of personalizing treatment based on individual patient characteristics for better outcomes," explained Inaba. 

Patients who would have otherwise been treated with high-risk therapy experienced fewer side effects, such as thrombosis and pancreatitis. The findings suggest that by using genome- and early treatment response-guided risk classification, clinicians and researchers can accurately identify patients who are likely to benefit from less intensive treatment.

"We now have tangible evidence that reduced therapy can be beneficial for some patients, which decreases toxicity," said Purvis. "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. We're proud that we can achieve this for most of our leukemia patients, which is truly remarkable." 

Authors and funding

The study's other authors are Yinmei Zhou, Seth Karol, Jeffrey Rubnitz, Raul Ribeiro, Jun Yang, Lu Wang, Stephanie Dixon, Kathryn Roberts, Qingsong Gao, Cheng Cheng, Charles Mullighan, Sima Jeha, Ching-Hon Pui, all of St. Jude; W. Paul Bowman, Cook Children's Medical Center; and Shawn Lee formerly of St. Jude and now of Yong Loo Lin School of Medicine and Khoo Teck Puat-National University Children's Medical Institute.

The study was supported by grants from the National Cancer Institute (Cancer Center Support

CORE Grant CA021765 and R35 CA197695), the St. Jude Children's Research Hospital Chromatin Collaborative, and ALSAC, the fundraising and awareness organization of St. Jude.

Source:

Journal reference:

Purvis, K., et al. (2024) Outcomes in patients with ETV6::RUNX1 or high-hyperdiploid B-ALL treated in the St. Jude Total Therapy XV/XVI studies. Blood. Doi.Org/10.1182/blood.2024024936.

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