The level of residual disease based on mutant NPM1 is an independent prognostic factor for relapse and survival in AML.

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

Blood

journal_title

Blood

authors

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-2012-10-461749

subject

Has Abstract

pub_date

2013-07-04 00:00:00

pages

83-92

issue

1

eissn

0006-4971

issn

1528-0020

pii

blood-2012-10-461749

journal_volume

122

pub_type

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