title: Early prediction of therapy response in patients with acute myeloid leukemia by nucleosomal DNA fragments.
abstract: BACKGROUND
  Elevated levels of nucleosomal DNA fragments can be detected in plasma and sera of patients with malignant diseases.
  
  
  METHODS
  We investigated the course of nucleosomal DNA, thymidine kinase, lactate dehydrogenase and leukocytes in sera of 25 patients with acute myeloid leukemia during the first cycle of induction chemotherapy and tested their power to distinguish between patients with complete remission and those with no remission.
  
  
  RESULTS
  Almost all patients showed strongly decreasing levels of nucleosomal DNA during the first week, in some cases after initial peaks. In overall analysis of variance, DNA levels could clearly distinguish between patients with complete remission, who had higher DNA values, and those with insufficient response (p = 0.017). The area under the curve of DNA values of days 2-4 after start of therapy (AUC 2-4) discriminated between both groups with a sensitivity of 56% at a specificity of 100%. Further, pretherapeutic levels and AUC 2-4 of nucleosomal DNA correlated significantly with blast reduction after 16 days. A tendency to higher levels in patients with complete response was also found for thymidine kinase, lactate dehydrogenase and leukocytes, however the difference did not reach the level of significance (p = 0.542, p = 0.260, and p = 0.144, respectively).
  
  
  CONCLUSIONS
  Our results indicate that nucleosomal DNA fragments are valuable markers for the early prediction of therapeutic efficacy in patients with acute myeloid leukemia.
authors.affiliation: Institute of Clinical Chemistry, University Hospital Munich-Grosshadern, Marchioninistr, 15, D-81377 Munich, Germany. mueller_susanne@yahoo.de
authors.forename: Susanne
authors.initials: S
authors.lastname: Mueller
authors.forename: Stefan
authors.initials: S
authors.lastname: Holdenrieder
authors.forename: Petra
authors.initials: P
authors.lastname: Stieber
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
authors.forename: Andreas
authors.initials: A
authors.lastname: Schalhorn
authors.forename: Jan
authors.initials: J
authors.lastname: Braess
authors.forename: Dorothea
authors.initials: D
authors.lastname: Nagel
authors.forename: Dietrich
authors.initials: D
authors.lastname: Seidel
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D003561:Cytarabine / Q000008:administration & dosage; D053938:DNA Fragmentation; D003630:Daunorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000032:analysis / Q000097:blood; D007951:Leukemia, Myeloid / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D007962:Leukocytes; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009707:Nucleosomes / Q000737:chemistry; D011237:Predictive Value of Tests; D011379:Prognosis; D013866:Thioguanine / Q000008:administration & dosage; D013937:Thymidine Kinase / Q000097:blood; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D009707:Nucleosomes; D003561:Cytarabine; D008942:Mitoxantrone; D007770:L-Lactate Dehydrogenase; D013937:Thymidine Kinase; D013866:Thioguanine; D003630:Daunorubicin