Adjusting treatment based on early response to chemotherapy made a life-saving difference to young patients with an acute lymphoblastic leukemia (ALL) subtype, according to a new study whose results are good news for children and adolescents with Philadelphia chromosome-like ALL (Ph-like ALL), a subtype that until now was associated with a poor prognosis. Ph-like ALL accounts for as much as 15% of cases of the most common pediatric cancer, B-ALL, which affects the B lymphocytes.
The study, led by Ching Hon-Pui, MD, chair of the St. Jude Children’s Research Hospital Department of Oncology in Memphis, Tennessee, involved 344 children and adolescents with B-ALL, including 40 with the Ph-like ALL subtype. All were enrolled in a St. Jude clinical trial that used risk-directed chemotherapy. The approach relied on a method pioneered at St. Jude to monitor and adjust treatment intensity based on the percentage of leukemic cells, known as minimal residual disease (MRD), in patient bone marrow at days 19 and 42 of chemotherapy.
Using MRD-based, risk-directed chemotherapy, patients in this study had high rates of long-term and cancer-free survival regardless of their leukemia subtype. Overall, 92.5% of patients with Ph-like ALL in this study were alive 5 years after their cancer was discovered compared to 95.1% of other B-ALL patients.
“This study shows that by measuring minimal residual disease and using the results to guide treatment intensity, patients with Ph-like ALL can enjoy the same high rates of survival as other patients,” said Hon-Pui. The study appeared in the Journal of Clinical Oncology (2014; doi:10.1200/JCO.2014.55.4105).
When available, more sophisticated genetic testing should be used to identify which of the B-ALL patients with high levels of MRD have the Ph-like ALL subtype, Pui said. That is because many patients with Ph-like ALL have genetic alterations that leave cancer cells vulnerable to available cancer drugs called ABL tyrosine kinase inhibitors (TKIs) and possibly other targeted therapies that are still experimental. Unlike conventional chemotherapy, TKIs kill more selectively and are less likely to damage healthy cells. Pui estimated that 20% of pediatric patients with Ph-like ALL might be candidates for TKIs.
“In the future, genetic testing will likely be used at diagnosis to identify Ph-like ALL and direct patients to the best targeted therapy, possibly including some drugs that are currently experimental,” he said.
Previous studies of Ph-like ALL focused on high-risk patients whose treatment did not include risk-directed therapy based on MRD levels. This study included all eligible patients with new B-ALL diagnoses who enrolled in the St Jude Total Therapy XV study between June 2000 and October 2007. Genomic testing was used to retrospectively diagnose Ph-like ALL. MRD proved essential for identifying patients with Ph-like ALL who can be cured with less-intensive chemotherapy.