期刊
JOURNAL OF CLINICAL ONCOLOGY
卷 28, 期 23, 页码 3724-3729出版社
AMER SOC CLINICAL ONCOLOGY
DOI: 10.1200/JCO.2010.28.6468
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资金
- Deutsche Jose Carreras Leukamie-Stiftung, Germany [R00/18, R04/26f]
- Bundesministerium fur Bildung und Forschung, Germany [01GI9981]
Purpose To evaluate the prognostic impact of minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) expressing the CBFB-MYH11 fusion transcript. Patients and Methods Quantitative reverse transcriptase polymerase chain reaction (PCR) was performed on 684 bone marrow (BM; n = 331) and/or peripheral blood (PB; n = 353) samples (median, 13 samples per patient) from 53 younger adult (16 to 60 years old) patients with AML treated in prospective German-Austrian AML Study Group treatment trials. Samples were obtained at diagnosis (BM, n = 45; PB, n = 48), during treatment course (BM, n = 153; PB, n = 122), and at follow-up (BM, n = 133; PB, n = 183). To evaluate the applicability of PB for MRD detection, 198 paired BM and PB samples obtained at identical time points were analyzed. Results The following three clinically relevant checkpoints were identified during consolidation and early follow-up that predicted relapse: achievement of PCR negativity in at least one BM sample during consolidation therapy (2-year relapse-free survival [RFS], 79% v 54% for PCR positivity; P = .035); achievement of PCR negativity in at least two BM or PB samples during consolidation therapy and early follow-up (<= 3 months; 2-year RFS, P = .001; overall survival, P = .01); and conversion from PCR negativity to PCR positivity with copy ratios of more than 10 after consolidation therapy. Analysis of paired BM and PB samples revealed BM samples to be more sensitive during the course of therapy, whereas for follow-up, PB samples were equally informative. Conclusion We defined clinically relevant MRD checkpoints that allow for the identification of patients with CBFB-MYH11-positive AML who are at high risk of relapse. Monitoring of CBFB-MYH11 transcript levels should be incorporated into future clinical trials to guide therapeutic decisions. J Clin Oncol 28: 3724-3729. (C) 2010 by American Society of Clinical Oncology
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