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

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 iden...

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Bibliographic Details
Published in:Annals of hematology 2018-10, Vol.97 (10), p.1757-1765
Main Authors: Bill, Marius, Grimm, Juliane, Jentzsch, Madlen, Kloss, Laura, Goldmann, Karoline, Schulz, Julia, Beinicke, Stefanie, Häntschel, Janine, Cross, Michael, Vucinic, Vladan, Pönisch, Wolfram, Behre, Gerhard, Franke, Georg-Nikolaus, Lange, Thoralf, Niederwieser, Dietger, Schwind, Sebastian
Format: Article
Language:English
Subjects:
Adult
Aged
Allografts
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biomarkers, Tumor - analysis
Biomarkers, Tumor - blood
Bone Marrow - chemistry
Bone Marrow Transplantation
CCAAT-Enhancer-Binding Proteins - analysis
Combined Modality Therapy
DNA, Neoplasm - genetics
Female
fms-Like Tyrosine Kinase 3 - analysis
Hematology
Humans
Leukemia
Leukemia, Myeloid, Acute - genetics
Leukemia, Myeloid, Acute - mortality
Leukemia, Myeloid, Acute - pathology
Leukemia, Myeloid, Acute - therapy
Male
Medical prognosis
Medicine
Medicine & Public Health
Middle Aged
Mutation
Neoplasm Proteins - analysis
Neoplasm Proteins - blood
Neoplasm Proteins - genetics
Neoplasm, Residual
Nuclear Proteins - analysis
Nuclear Proteins - blood
Nuclear Proteins - genetics
Oncology
Original Article
Peripheral Blood Stem Cell Transplantation
Polymerase Chain Reaction - methods
Preoperative Care
Prognosis
Recurrence
Remission Induction
Retrospective Studies
Sensitivity and Specificity
Stem cell transplantation
Stem cells
Transplantation Conditioning - methods
Transplants & implants
Treatment Outcome
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Summary: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  
ISSN:0939-5555
1432-0584
DOI:10.1007/s00277-018-3373-y