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).

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

Figure 1

Distribution of nucleosomal DNA in patients with complete remission and no remission during the first week of induction therapy (-- = medians).

Figure 2

The area under the curve of nucleosomal DNA values of days 2–4 of induction therapy (AUC 2–4) discriminates between patients with complete remission and those with no remission. A) AUC 2–4 of nucleosomal DNA is significantly larger for patients with complete response (CR ■) than for those not responsive (no CR ●) to therapy (p = 0.042). Here, median levels of days 1 to 4 and the respective AUC 2–4 are shown for both response groups. B) Distribution of AUC 2–4 levels of nucleosomal DNA. Favourable therapy response can be predicted with a sensitivity of 56% and a specificity of 100% at a cutoff level of 150 ng/mL*d.