Abstract:
:Mutations of the NPM1 gene (NPM1mut) are among the most common genetic alterations in acute myeloid leukemia and are suitable for minimal residual disease detection. We retrospectively investigated the prognostic impact of NPM1mut-based minimal residual disease detection from bone marrow for development of relapse by using a newly developed real-time polymerase chain reaction based on locked nucleic acid-containing primers in 174 patients, 155 of whom were treated within prospective protocols. The prognostic value of 5 cutoff values after completion of treatment or after allogeneic transplantation was studied by using cause-specific hazard models. Subsequent validation using cross-validated partial likelihood analysis revealed that an increase of more than 1% NPM1mut/ABL1 was most prognostic for relapse after chemotherapy, whereas an increase of more than 10% NPM1mut/ABL1 was most prognostic for relapse after allogeneic transplantation. Univariate and multivariate analysis of disease-free survival and overall survival revealed a significantly worse outcome in patients with >1% NPM1mut/ABL1 and >10% NPM1mut/ABL1, respectively, which remained significant after adjustment for FLT3-internal tandem duplication status. Our results in a large data set define and optimize cutoff values for early diagnosis of molecular relapse. These results may be especially important for defining triggers for early therapeutic intervention.
journal_name
Bloodjournal_title
Bloodauthors
Shayegi N,Kramer M,Bornhäuser M,Schaich M,Schetelig J,Platzbecker U,Röllig C,Heiderich C,Landt O,Ehninger G,Thiede C,Study Alliance Leukemia (SAL).doi
10.1182/blood-2012-10-461749subject
Has Abstractpub_date
2013-07-04 00:00:00pages
83-92issue
1eissn
0006-4971issn
1528-0020pii
blood-2012-10-461749journal_volume
122pub_type
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