title: Minimal residual disease detection defined as the malignant fraction of the total primitive stem cell compartment offers additional prognostic information in acute myeloid leukaemia.
abstract: BACKGROUND
  Immunophenotypic detection of minimal residual disease (MRD) in bone marrow (BM) of acute myeloid leukaemia (AML) patients is of high prognostic relevance. Standard MRD percentage is assessed as a percentage of total white blood cells (WBCs) and is therefore highly dependent on WBC count. Peripheral blood (PB) contains more than five times lower MRD percentages. Therefore, PB in BM aspirates cause dilution of the MRD cells, possibly leading to false-negative results for BM MRD. The latter is avoided when relating the fraction of malignant primitive cells, identified by aberrant marker expression [aberrant primitive cells (aPC)], to the total population of primitive cells. Such a fraction may in addition reflect an important biological parameter.
  
  
  METHODS
  As this approach is thus independent of WBC count and the total size of the primitive compartment, we investigated the role of aPC fractions on overall and relapse-free survival (RFS) in 98 patients with AML under the age of 60.
  
  
  RESULTS
  We show that this approach identifies MRD-negative (as defined by % of WBC) but aPC-positive (as defined by % of primitive cells) patients with poor outcome after both first and second induction cycle of chemotherapy.
  
  
  CONCLUSIONS
  As a result, in cases with a primitive marker present, RFS is best predicted when combining standard MRD percentage with aPC fractions.
authors.affiliation: Department of Haematology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Terwijn
authors.forename: A
authors.initials: A
authors.lastname: Kelder
authors.forename: A N
authors.initials: AN
authors.lastname: Snel
authors.forename: A P
authors.initials: AP
authors.lastname: Rutten
authors.forename: W J
authors.initials: WJ
authors.lastname: Scholten
authors.forename: Y J M
authors.initials: YJ
authors.lastname: Oussoren
authors.forename: A A
authors.initials: AA
authors.lastname: Van De Loosdrecht
authors.forename: S
authors.initials: S
authors.lastname: Zweegman
authors.forename: G J
authors.initials: GJ
authors.lastname: Ossenkoppele
authors.forename: G J
authors.initials: GJ
authors.lastname: Schuurhuis
mesh_terms: D002675:Child, Preschool; D005188:False Negative Reactions; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000503:physiopathology*; D008875:Middle Aged; D015999:Multivariate Analysis; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000473:pathology; D011379:Prognosis; D012015:Reference Standards