Slower molecular response to treatment predicts poor outcome in patients with TEL/AML1 positive acute lymphoblastic leukemia
2002; Wiley; Volume: 97; Issue: 1 Linguagem: Inglês
10.1002/cncr.11043
ISSN1097-0142
AutoresJozef Madžo, Jan Zuna, Kateřina Mužíková, Markéta Kalinová, Ondřej Krejčí, Ondřej Hrušák, B Otová, Jan Starý, Jan Trka,
Tópico(s)Chronic Myeloid Leukemia Treatments
ResumoAbstract 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 ≥ 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
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