Early prediction of therapy response in patients with acute myeloid leukemia by nucleosomal DNA fragments.
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.
Mueller
Susanne
S
Institute of Clinical Chemistry, University Hospital Munich-Grosshadern, Marchioninistr, 15, D-81377 Munich, Germany. mueller_susanne@yahoo.de
Holdenrieder
Stefan
S
Stieber
Petra
P
Haferlach
Torsten
T
Schalhorn
Andreas
A
Braess
Jan
J
Nagel
Dorothea
D
Seidel
Dietrich
D
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
D014408:Biomarkers, Tumor; D009707:Nucleosomes; D003561:Cytarabine; D008942:Mitoxantrone; D007770:L-Lactate Dehydrogenase; D013937:Thymidine Kinase; D013866:Thioguanine; D003630:Daunorubicin