Real-Time Classification Finds High-Risk ALL With Favorable Outcomes

Real-time classification can identify a previously unrecognized subset of high-risk patients with childhood B-cell acute lymphoblastic leukemia (ALL) who have excellent chances for cure without further intensification of treatment, according to a new study.

Adjusting the intensity of treatment based on the patient’s likelihood of relapse has emerged as a promising strategy for treating children with ALL. “Refinements in risk classification have contributed to overall improvements in ALL outcomes,” said lead author Elizabeth Raetz, MD, of Huntsman Cancer Institute and Primary Children's Hospital at the University of Utah in Salt Lake City. “Risk groups at diagnosis determine treatment intensity, identify patients at higher risk of relapse so treatment can be intensified, and identify patients who do well with less intensive therapy to minimize acute toxicities and late effects.”

Dr. Raetz presented the results at the 57th Annual American Society of Hematology (ASH) Meeting and Exposition, held December 5–8 in Orlando, Florida (abstract 807).

She noted that this is the first Children’s Oncology Group (COG) study to systematically assess minimal residual disease (MRD) at the end of induction therapy and use this in concert with clinical and biological data for risk stratification and treatment assignment.

In the study, newly diagnosed B-cell ALL patients between age 1 and 30 received either standard-risk or high-risk initial chemotherapy regimens based on the National Cancer Institute (NCI) risk definitions. The patients underwent standardized testing to detect cytogenetic abnormalities associated with favorable and unfavorable outcomes.

Dr. Raetz and colleagues classified 5,104 NCI standard-risk and 2,791 NCI high-risk patients into low (29%), standard (33%), high (34%), or very high (4%) risk groups at the end of induction therapy, based on the presence of favorable and unfavorable cytogenetic findings and early treatment response.

They found that the 5-year event-free survival (EFS) was higher for rapid early responders (89.3%) as compared to slow early responders (67.9%). The 5-year EFS varied according to genetic subset, ranging from 70% for those with unfavorable cytogenetics to 95% for those with favorable cytogenetic abnormalities.

Similarly, the 5-year overall survival was higher in rapid responders (95.2%) than in slow responders (84.3%). Those with either standard-risk or high-risk disease and favorable cytogenetic findings, who accounted for almost half of all patients, had a 98% likelihood of being alive 5 years after diagnosis.

“We were surprised that high-risk patients who were rapid responders had a 94.5% EFS and 98% overall survival,” she said.

In conclusion, Dr. Raetz said: “Real‐time classification incorporating clinical features, blast cytogenetics, and early response was feasible in close to 10,000 patients enrolled on COG ALL trials, and identified patients with varying outcomes for risk‐based treatment allocation. Early response by marrow morphology was not prognostic when MRD response was used, and therefore is no longer used in COG studies. Outcomes in high-risk B‐ALL patients who have no evidence of CNS leukemia and also have rapid MRD responses are excellent with contemporary therapy, which suggests that these patients will not benefit from further chemotherapy intensification.”