title: Minimal residual disease diagnostics in patients with acute myeloid leukemia in the post-transplant period: comparison of peripheral blood and bone marrow analysis.
abstract: Considering the high relapse rates of AML after allogeneic hematopoietic stem cell transplant, research aims to improve post-transplant surveillance. To determine the value of peripheral blood (PB) for post-transplant minimal residual disease monitoring, we compared 38 PB and bone marrow (BM) sample pairs in 25 stem cell recipients with NPM1-mutated AML (12 males, 13 females, ages 21-73 years). NPM1A mutation levels and chimerism ratios were determined in non-separated BM/PB. We observed congruent results in 28/38 (74%). In 14/38 sample pairs (37%), BM and PB were negative for the NPM1A mutation. Fourteen sample pairs were positive in BM and PB, albeit at higher mutation levels in the BM in 11 cases (4- to 278-fold). Results were discordant in 10 cases (26%), with weakly positive mutation levels in the BM but negative levels in the PB. Cases with ≥0.2% NPM1A mutation level in BM were always positive in PB. Chimerism was concordant in BM and PB in 21/34 (62%) of sample pairs. In conclusion, MRD monitoring with qPCR for the NPM1 mutation and chimerism from non-separated PB contributes to surveillance in patients with AML in the post-transplant period, but even with highly sensitive qPCR there is a risk of failure to detect the mutation in PB.
authors.affiliation: Clinic for Stem Cell Transplantation, University Cancer Center Hamburg, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Stahl
authors.forename: Anita
authors.initials: A
authors.lastname: Badbaran
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kröger
authors.forename: Evgeny
authors.initials: E
authors.lastname: Klyuchnikov
authors.forename: Tatjana
authors.initials: T
authors.lastname: Zabelina
authors.forename: Silke
authors.initials: S
authors.lastname: Zeschke
authors.forename: Philippe
authors.initials: P
authors.lastname: Schafhausen
authors.forename: Waltraud
authors.initials: W
authors.lastname: Schultz
authors.forename: Svetlana
authors.initials: S
authors.lastname: Asenova
authors.forename: Anna
authors.initials: A
authors.lastname: Smirnova
authors.forename: Christine
authors.initials: C
authors.lastname: Wolschke
authors.forename: Francis
authors.initials: F
authors.lastname: Ayuk
authors.forename: Axel R
authors.initials: AR
authors.lastname: Zander
authors.forename: Boris
authors.initials: B
authors.lastname: Fehse
authors.forename: Ulrike
authors.initials: U
authors.lastname: Bacher
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007951:Leukemia, Myeloid / Q000097:blood / Q000235:genetics / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D016133:Polymerase Chain Reaction; D011184:Postoperative Period; D018183:Transplantation Chimera / Q000097:blood; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin