Pretransplant NPM1 MRD levels predict outcome after allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia

The objective was to evaluate the prognostic impact of pre-transplant minimal residual disease (MRD) as determined by real-time quantitative polymerase chain reaction in 67 adult NPM1-mutated acute myeloid leukemia patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). Twenty-...

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Main Authors: Kayser, Sabine (Author) , Stadtherr, Peter (Author) , Uppenkamp, Michael (Author) , Bochtler, Tilmann (Author) , Hegenbart, Ute (Author) , Ho, Anthony Dick (Author) , Dreger, Peter (Author) , Krämer, Alwin (Author)
Format: Article (Journal)
Language:English
Published: 29 July 2016
In: Blood cancer journal
Year: 2016, Volume: 6, Issue: 7, Pages: 1-7
ISSN:2044-5385
DOI:10.1038/bcj.2016.46
Online Access:Verlag, Volltext: http://dx.doi.org/10.1038/bcj.2016.46
Verlag, Volltext: https://www.nature.com/articles/bcj201646
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Author Notes:S. Kayser, A. Benner, C. Thiede, U. Martens, J. Huber, P. Stadtherr, J.W.G. Janssen, C. Röllig, M.J. Uppenkamp, T. Bochtler, U. Hegenbart, G. Ehninger, A.D. Ho, P. Dreger and A. Krämer

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520 |a The objective was to evaluate the prognostic impact of pre-transplant minimal residual disease (MRD) as determined by real-time quantitative polymerase chain reaction in 67 adult NPM1-mutated acute myeloid leukemia patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). Twenty-eight of the 67 patients had a FLT3-ITD (42%). Median age at transplantation was 54.7 years, median follow-up for survival from time of allografting was 4.9 years. At transplantation, 31 patients were in first, 20 in second complete remission (CR) and 16 had refractory disease (RD). Pre-transplant NPM1 MRD levels were measured in 39 CR patients. Overall survival (OS) for patients transplanted in CR was significantly longer as compared to patients with RD (P=0.004), irrespective of whether the patients were transplanted in first or second CR (P=0.74). There was a highly significant difference in OS after allogeneic HSCT between pre-transplant MRD-positive and MRD-negative patients (estimated 5-year OS rates of 40 vs 89%; P=0.007). Multivariable analyses on time to relapse and OS revealed pre-transplant NPM1 MRD levels >1% as an independent prognostic factor for poor survival after allogeneic HSCT, whereas FLT3-ITD had no impact. Notably, outcome of patients with pre-transplant NPM1 MRD positivity >1% was as poor as that of patients transplanted with RD. 
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