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). Conclusion: Our results
indicate that nucleosomal DNA fragments are valuable markers for
the early prediction of therapeutic efficacy in patients with acute
myeloid leukemia.