Slower molecular response to treatment predicts poor outcome in patients with TEL/AML1 positive acute lymphoblastic leukemia

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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 (< 10−4; i.e., 1 or more leukemic cell per 104 normal cells), and another 13% of patients were positive at the level of 10−2 to 10−4 cells. No patient showed MRD 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. Cancer 2003;97:105–13. © 2003 American Cancer Society. DOI 10.1002/cncr.11043
Funding Information
  • Czech Ministry of Health (6509-3, 6406-3)
  • Charles University (57)
  • Agency of the Czech Republic (301/P055)
  • Czech Ministry of Education Programs (111300001, 111300003, 111300005)