Minimal residual disease diagnostics in patients with acute myeloid leukemia in the post-transplant period: comparison of peripheral blood and bone marrow analysis

Leuk Lymphoma. 2010 Oct;51(10):1837-43. doi: 10.3109/10428194.2010.508822.

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.

Publication types

  • Comparative Study

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Bone Marrow / metabolism
  • Bone Marrow / pathology
  • Disease-Free Survival
  • Female
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Leukemia, Myeloid / blood
  • Leukemia, Myeloid / genetics
  • Leukemia, Myeloid / surgery*
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm, Residual / diagnosis*
  • Neoplasm, Residual / genetics
  • Nuclear Proteins / genetics
  • Nucleophosmin
  • Polymerase Chain Reaction
  • Postoperative Period
  • Transplantation Chimera / blood
  • Transplantation, Homologous
  • Young Adult

Substances

  • NPM1 protein, human
  • Nuclear Proteins
  • Nucleophosmin