ORLANDO – Cytogenetic profile and response to initial induction therapy can identify a subgroup of National Cancer Institute (NCI) high risk childhood B-lymphoblastic leukemia patients who have good outcomes, Dr. Elizabeth Raetz said, reporting results for her colleagues in the Children’s Oncology Group (COG).
Outcomes were excellent for patients with favorable cytogenetic features and rapid minimal residual disease responses during induction therapy, said Dr. Raetz, of Huntsman Cancer Institute and Primary Children’s Hospital, University of Utah, Salt Lake City. Notably, 5-year overall survival (OS) was over 98% for those with favorable cytogenetic subsets, nearly half of all patients, in a combined analysis of standard risk and high risk patients.
Mary Jo Dales
Dr. Elizabeth Raetz
The findings suggest that these patients would not benefit from further intensification of their chemotherapy, sparing them possible toxicity and late effects.
The COG used clinical, biologic, and early disease response measures to study 11,144 patients, aged 1-30 years, enrolled on the COG AALL03B1 classification study. Patients began either a standard risk 3-drug or high risk 4-drug induction therapy based on NCI risk group, she said at the annual meeting of the American Society of Hematology.
After induction therapy, patients were classified into low (29%), standard (33%), high (34%), or very high (4%) risk groups for treatment allocation. Variables used for risk classification included age, initial WBC, extramedullary disease status, blast cytogenetics, early treatment response based on bone marrow morphology and minimal residual disease in marrow at day 29.
Rapid early response was defined as having less than 5% blasts in bone marrow by day 15 plus flow cytometry-based minimal residual disease less than 0.1% on day 29 of induction. Those with either 5% or more blasts in their marrow at day 15 or minimal residual disease of 0.1% or more at day 29 were deemed slow early responders.
Of the 96% of patients evaluable for post-induction treatment assignment, 5104 (65%) were treated for NCI standard risk and 2791 were treated for NCI high-risk B-ALL.
Rapid early responses were seen in 84% and slow early responses in 16%. For those with rapid early responses, the 5-year event-free survival rates was 89% and the overall survival rate was 95%. For those with slow early responses, EFS was 68% and OS was 84%.
The standard risk and high risk groups were then combined and analyzed based on cytogenetic subtype. The favorable gene ETV6-RUNX1 was seen in 26% (1,928 patients) and associated with an EFS of 93% as compared to an EFS of 84% for the 5578 patients without ETV6-RUNX1. OS was 98% for positive patients and 92% for negative patients. In the 21% (1,483 patients) with the triple trisomy 4/10/17, EFS was 95% as compared to an EFS of 84% for the 5,603 patients without the trisomy. OS was 99% and 92%, respectively.
In a subsequent analysis using current COG minimum residual disease response measures – with rapid early response defined as day 8 blood minimal residual disease less than 1% and day 29 marrow minimal residual disease less than 0.01% – the 243 high risk patients who had favorable cytogenetics and no detectable leukemia cells in their CSF had 5 years EFS of 95% and OS of 98%.
Dr. Raetz had no relevant financial disclosures.
Abstract 807: Genetic and Response-Based Risk Classification Identifies a Subgroup of NCI High Risk Childhood B-Lymphoblastic Leukemia (HR B-ALL) with Outstanding Outcomes: A Report from the Children’s Oncology Group (COG).
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