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, 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: To investigate the prognostic role of pre-transplant cell-free DNA levels in allogeneic hematopoietic stem cell transplant recipients. Study Design: Retrospective cohort study. Methods: A total of 177 allogeneic hematopoietic stem cell transplant 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 by 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 cell-free DNA and age (p=0.018; r=0.177). Pre-transplant cell-free DNA levels were lower in bcr-abl (+) patients (p=0.001), while an adverse correlation was indicated between cell-free DNA and bcr-abl levels (p=0.001; r=−0.531). Acute lymphoblastic leukemia patients with bcr-abl positivity (p=0.001) or abnormal cytogenetics (p=0.038) represented significantly lower pre-transplant cell-free DNA 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 cell-free DNA levels (p=0.024). Overall survival was not statistically different between high- and low- cell-free DNA groups (45.2% vs 22.5; p=0.821). Conclusion: In general, low serum levels of pre-transplant çell-free DNA seem to be associated with transplant-related morbidities and may be considered an adverse prognostic factor for allogeneic hematopoietic stem cell transplant recipients.