Cellular Classification and Prognostic Variables
For NCI standard-risk patients (COG-AALL0932), patients will be stratified as low risk, standard (average) risk, or very high risk for end-induction treatment based on cytogenetics, day 8 peripheral blood MRD, and day 28 bone marrow MRD:
- Standard Risk - Low: Patients will be considered low risk if they have: (1) day 8 peripheral blood MRD less than 0.01%; (2) day 28 marrow MRD less than 0.01%; and (3) either ETV6-RUNX1 or hyperdiploidy with extra copies of chromosomes 4 and 10 (favorable genetics). No morphologic assessment of early response will be performed and extra copies of chromosome 17 will no longer be required for assignment to favorable cytogenetics.
- Standard Risk - Average: NCI standard-risk patients with: (1) favorable cytogenetics; (2) less than 0.01% peripheral blood MRD on day 8; and (3) less than 0.01% marrow MRD on day 28 will be assigned to an average risk subgroup. Patients with: (1) neither favorable nor unfavorable cytogenetics who have less than 1% MRD in peripheral blood on day 8; and (2) less than 0.01% marrow MRD on day 28 are also assigned to an average-risk subgroup.
- Standard Risk - Very High: All patients with marrow MRD greater than 0.01% on day 28, with the exception of patients with favorable cytogenetics, will be assigned to a very high-risk group. Favorable cytogenetic patients with day 28 marrow MRD greater than 0.01% and patients with neither favorable nor unfavorable cytogenetics with day 8 peripheral blood MRD greater than 1% and day 28 marrow MRD less than 0.01% also will be assigned to a high-risk subgroup.
The following cytogenetic findings will classify a patient as very high risk regardless of other findings:
- BCR-ABL1 fusion and/or t(9;22).
- Hypodiploidy (fewer than 44 chromosomes).
The Dana-Farber Cancer Institute ALL Consortium is also testing a new risk classification system for patients with precursor B-cell ALL. All patients are initially classified as either standard risk or high risk based on age, presenting leukocyte count, and the presence or absence of CNS disease. At the completion of a five-drug remission induction regimen (4 weeks from diagnosis), the level of MRD is determined. Patients with high MRD (?0.01) are classified as very high risk and receive a more intensive postremission consolidation. Patients with low MRD (<0.01) continue to receive treatment based on their initial risk-group classification. The goal of this new classification schema is to determine whether intensification of therapy will improve the outcome of patients with high MRD at the end of remission induction. Patients with T-cell ALL are treated as high risk, regardless of MRD status. All patients with MLL translocations or hypodiploidy (<44 chromosomes) are classified as very high risk, regardless of MRD status or phenotype. Patients with the Philadelphia chromosome are treated as high risk, but receive a tyrosine kinase inhibitor (imatinib) beginning mid-induction and are eligible for an allogeneic stem cell transplant in first remission.