Slower molecular response to treatment predicts poor outcome in patients with TEL/AML1 positive acute lymphoblastic leukemia - Prospective real-time quantitative reverse transcriptase-polymerase chain reaction study
Abstract
BACKGROUND. The translocation t(12;21)(p13;q22), which produces the TEL/AML1 fusion gene, is the most frequent chromosomal abnormality in patients with childhood acute lymphoblastic leukemia (ALL) and generally is associated with a favorable prognosis.
Furthermore, real-time quantitative-polymerase chain reaction (RQ-PCR)-based detection of TEL/AML1 represents an accurate technique for the reproducible assessment of minimal residual disease (MRD). METHODS.
The authors employed RQ-reverse transcriptase-PCR (RQ-RT-PCR) technology to analyze MRD levels in 57 newly diagnosed patients with TEL/AML1 positive ALL in a prospective study. RESULTS.
On Day + 33, a particularly important time point in terms of outcome prediction based on MRD monitoring, 75% of patients reached negativity, 13% of patients were positive at very low levels (= 10(-2) cells at this time. The data demonstrate that patients with TEL/AML1 positive ALL had a better response to induction chemotherapy on Day + 33 compared with a group of unselected patients with ALL (P = 0.0001).
However, four patients with TEL/AML1 positive ALL developed relapse disease. Remarkably, these children were positive for MRD on Day + 33 at a level between 10(-2) cells and 10(-4) (n = 3 patients) and at < 10(-4) (n = 1 patient).
Kaplan-Meier analysis of disease free survival showed the statistical significance of this distribution (MRD positive vs. MRD negative; log-rank P = 0.0016).
CONCLUSIONS. The authors conclude that, although the TEL/AML1 positive leukemias generally are associated with a favorable outcome, MRD positivity assessed by RQ-RT-PCR analysis at the end of induction therapy represents a significantly negative prognostic feature.