title: Minimal residual disease tests provide an independent predictor of clinical outcome in adult acute lymphoblastic leukemia.
abstract: OBJECTIVE
  Investigation of minimal residual disease (MRD) in childhood acute lymphoblastic leukemia (ALL) using molecular markers has proven superior to other standard criteria (age, sex, and WBC) in distinguishing patients at high, intermediate, and low risk of relapse. The aim of our study was to determine whether MRD investigation is valuable in predicting outcome in Philadelphia-negative adult patients with ALL.
  
  
  METHODS
  MRD was assessed in 85 adult patients with B-lineage ALL by semiquantitative immunoglobulin H gene analysis on bone marrow samples collected during four time bands in the first 24 months of treatment. Fifty patients received chemotherapy only and 35 patients received allogeneic (n = 19) or autologous (n = 16) bone marrow transplantation (BMT) in first clinical remission. The relationship between MRD status and clinical outcome was investigated and compared with age, sex, immunophenotype, and presenting WBC count.
  
  
  RESULTS
  Fisher's exact test established a statistically significant concordance between MRD results and clinical outcome at all times. Disease-free survival (DFS) rates for MRD-positive and -negative patients and log-rank testing established that MRD positivity was associated with increased relapse rates at all times (P <.05) but was most significant at 3 to 5 months after induction and beyond. MRD status after allogeneic BMT rather than before was found to be an important predictor of outcome in 19 adult patients with ALL tested. In patients receiving autologous BMT (n = 16), the MRD status before BMT was more significant (P =.005).
  
  
  CONCLUSIONS
  The association of MRD test results and DFS was independent of and greater than other standard predictors of outcome and is therefore important in determining treatment for individual patients.
authors.affiliation: Department of Hematology, Royal Free and University College School of Medicine, London, United Kingdom.
authors.forename: Forida Y
authors.initials: FY
authors.lastname: Mortuza
authors.forename: Mary
authors.initials: M
authors.lastname: Papaioannou
authors.forename: Ilidia M
authors.initials: IM
authors.lastname: Moreira
authors.forename: Luke A
authors.initials: LA
authors.lastname: Coyle
authors.forename: Paula
authors.initials: P
authors.lastname: Gameiro
authors.forename: Domenica
authors.initials: D
authors.lastname: Gandini
authors.forename: H Grant
authors.initials: HG
authors.lastname: Prentice
authors.forename: Anthony
authors.initials: A
authors.lastname: Goldstone
authors.forename: A Victor
authors.initials: AV
authors.lastname: Hoffbrand
authors.forename: Letizia
authors.initials: L
authors.lastname: Foroni
mesh_terms: D000328:Adult; D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D016026:Bone Marrow Transplantation; D004273:DNA, Neoplasm / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis; D016130:Immunophenotyping; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology*; D011237:Predictive Value of Tests; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors; D012737:Sex Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D007136:Immunoglobulins