Journal
EXPERIMENTAL HEMATOLOGY
Volume 37, Issue 1, Pages 135-142Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.exphem.2008.09.014
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Background. Minimal residual disease (MRD) diagnostics in acute myeloid leukemia (AML) gain increasing importance after allogeneic stem cell transplantation (SCT). Nucleophosmin (NPM1) mutations, with their high frequency in AML, were suggested to represent suitable MRD markers, but so far no study has evaluated their usefulness in the posttransplantation period. Materials and Methods. We evaluated the validity of this MRD marker in the posttransplantation period in a cohort or 13 patients with an NPM1A mutation (NPM1Amut). For this most frequent NPM1A subtype., quantitative real-time polymerase chain reaction (qPCR), was retrospectively performed oil bone marrow/peripheral blood samples that had been taken before and after SCT, Results. NPM1Amut was retrospectively followed up in 13 patients who received 14 transplantations. One-hundred and thirty-nine qPCR analyses were performed (median: 7 time points; median follow-up: 216 days; range, 35-1825 days). After SCT, 10 of 14 NPM1Amut cases (71%) became PCR-negative, of which four achieved stable remissions. All four patients (29%) who remained NPM1Amut-positive after SCT relapsed. In all nine relapse cases, increases of NPM1Amut were seen that preceded morphological relapse and the decrease of molecular chimerism with mean intervals of 24 days (range, 12-38 days) and 15 days (range, 1-36 days), respectively. Conclusions. Quantitative assessment of NPM1Amut seems to provide a reliable MRD marker in the positransplantation period, predicting relapse earlier than morphology or molecular chimerism, which should be confirmed in larger studies. (C) 2009 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.
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