The Impact of Pre-transplant Cell-free DNA Levels on Leukemia Relapse and Transplant Related Complications in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Background: Cell free DNA (cfDNA), which may be considered as "liquid" biopsy, may serve as a diagnostic and prognostic marker not only in hematological malignancies but in solid tumors as well. Aims: The aim of this study is to investigate the prognostic role of pre-transplant cfDNA levels in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. Study Design: This study is a retrospective cohort study. Methods: A total of 177 allo-HSCT recipients median age: 36(16-66) years; male/female: 111/66 with an initial diagnosis of acute leukemia were included in the study. Cell free DNA was extracted from pre-transplant serum samples using the MagNA Pure Compact Nucleic Acid Isolation Kit I with the MagNA Pure Compact instrument (Roche Diagnostics, Penzberg, Germany). Results: A positive correlation was demonstrated between cfDNA and age (p=0.018; r=0.177). Pre-transplant cfDNA levels were found to be lower in bcr-abl (+) patients (p=0.001), whilst an adverse correlation was indicated between cfDNA and bcr-abl levels (p=0.001; r=-0.531). Akut lymphoblastic leukemia patients with bcr-abl positivity (p=0.001) or abnormal cytogenetics (p=0.038) represented signficantly lower pre-transplant cfDNA levels. Cell free DNA levels were lower in patients who developed sinusoidal obstruction syndrome (p=0.035). In terms of long term complications, acute myeloid leukemia patients who experienced post-transplant relapse had significantly lower pre-transplant cfDNA levels (p=0.024). Overall survival was not statistically different between high- and low-cfDNA groups (45.2% vs 22.5; p=0.821). Conclusion: In general, lower serum levels of pre-transplant cfDNA seem to be associated with transplant related morbidities and may be considered as an adverse prognostic factor for allo-HSCT recipients.