Minimal residual disease diagnostics in patients with acute myeloid leukemia in the post-transplant period: comparison of peripheral blood and bone marrow analysis.
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.
Stahl
Tanja
T
Clinic for Stem Cell Transplantation, University Cancer Center Hamburg, Germany.
Badbaran
Anita
A
Kröger
Nicolaus
N
Klyuchnikov
Evgeny
E
Zabelina
Tatjana
T
Zeschke
Silke
S
Schafhausen
Philippe
P
Schultz
Waltraud
W
Asenova
Svetlana
S
Smirnova
Anna
A
Wolschke
Christine
C
Ayuk
Francis
F
Zander
Axel R
AR
Fehse
Boris
B
Bacher
Ulrike
U
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
C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin