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.

Cancer 2003 Jan;97(1):105-13

Childhood Leukemia Investigation Prague, Prague, Czech Republic.

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 10(4) normal cells), and another 13% of patients were positive at the level of 10(-2) to 10(-4) cells. No patient showed MRD levels > or = 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.

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http://dx.doi.org/10.1002/cncr.11043DOI Listing
January 2003
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References

(Supplied by CrossRef)
TEL/AML1 fusion resulting from a cryptic t(12;21) is the most common genetic lesion in pediatric ALL and defines a subgroup of patients with an excellent prognosis
Shurtleff et al.
Leukemia. 1995
Incidence of TEL/AML1 fusion in children with relapsed acute lymphoblastic leukemia
Loh et al.
Blood. 1998
Incidence of TEL/AML1 fusion gene analyzed consecutively in children with acute lymphoblastic leukemia in relapse
Harbott et al.
Blood. 1997
TEL-AML1 fusion transcript in relapsed childhood acute lymphoblastic leukemia
Seeger et al.
Blood. 1998

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