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22.05.2018 | Original Article

Digital droplet PCR-based absolute quantification of pre-transplant NPM1 mutation burden predicts relapse in acute myeloid leukemia patients

verfasst von: Marius Bill, Juliane Grimm, Madlen Jentzsch, Laura Kloss, Karoline Goldmann, Julia Schulz, Stefanie Beinicke, Janine Häntschel, Michael Cross, Vladan Vucinic, Wolfram Pönisch, Gerhard Behre, Georg-Nikolaus Franke, Thoralf Lange, Dietger Niederwieser, Sebastian Schwind

Erschienen in: Annals of Hematology | Ausgabe 10/2018

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Abstract

Allogeneic hematopoietic stem cell transplantation is an established consolidation therapy for patients with acute myeloid leukemia. However, relapse after transplantation remains a major clinical problem resulting in poor prognosis. Thus, detection of measurable (“minimal”) residual disease to identify patients at high risk of relapse is essential. A feasible method to determine measurable residual disease may be digital droplet PCR (ddPCR) that allows absolute quantification with high sensitivity and specificity without the necessity of standard curves. Using ddPCR, we analyzed pre-transplant peripheral blood and bone marrow of 51 NPM1-mutated acute myeloid leukemia patients transplanted in complete remission or complete remission with incomplete recovery. Mutated NPM1 measurable residual disease-positive patients had higher cumulative incidence of relapse (P < 0.001) and shorter overall survival (P = 0.014). Restricting the analyses to patients receiving non-myeloablative conditioning, mutated NPM1 measurable residual disease positivity is associated with higher cumulative incidence of relapse (P < 0.001) and shorter overall survival (P = 0.006). Positive mutated NPM1 measurable residual disease status determined by ddPCR before allogeneic stem cell transplantation is associated with worse prognosis independent of other known prognostic markers—also for those receiving non-myeloablative conditioning. In the future, mutated NPM1 measurable residual disease status determined by ddPCR might guide treatment and improve patients’ outcomes.

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Titel: Digital droplet PCR-based absolute quantification of pre-transplant NPM1 mutation burden predicts relapse in acute myeloid leukemia patients
verfasst von: Marius Bill
Juliane Grimm
Madlen Jentzsch
Laura Kloss
Karoline Goldmann
Julia Schulz
Stefanie Beinicke
Janine Häntschel
Michael Cross
Vladan Vucinic
Wolfram Pönisch
Gerhard Behre
Georg-Nikolaus Franke
Thoralf Lange
Dietger Niederwieser
Sebastian Schwind
Publikationsdatum: 22.05.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Annals of Hematology / Ausgabe 10/2018
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-018-3373-y

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