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

Abstract

Background: Cell-free DNA, which may be considered as “liquid”biopsy, may serve as a diagnostic and prognostic marker not only inhematological malignancies but in solid tumors as well.Aims: To investigate the prognostic role of pre-transplant cell-freeDNA levels in allogeneic hematopoietic stem cell transplant recipients.Study Design: Retrospective cohort study.Methods: A total of 177 allogeneic hematopoietic stem cell transplantrecipients [median age: 36 (16-66) years; male/female: 111/66] withan initial diagnosis of acute leukemia were included in the study.Cell-free DNA was extracted from pre-transplant serum samples byusing the MagNA Pure Compact Nucleic Acid Isolation Kit I withthe MagNA Pure Compact instrument (Roche Diagnostics, Penzberg,Germany).Results: A positive correlation was demonstrated between cell-freeDNA and age (p=0.018; r=0.177). Pre-transplant cell-free DNAlevels were lower in bcr-abl (+) patients (p=0.001), while an adversecorrelation was indicated between cell-free DNA and bcr-abl levels(p=0.001; r=−0.531). Acute lymphoblastic leukemia patients withbcr-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 sinusoidalobstruction syndrome (p=0.035). In terms of long-term complications,acute myeloid leukemia patients who experienced post-transplantrelapse had significantly lower pre-transplant cell-free DNA levels(p=0.024). Overall survival was not statistically different betweenhigh- and low- cell-free DNA groups (45.2% vs 22.5; p=0.821).Conclusion: In general, low serum levels of pre-transplant çellfree DNA seem to be associated with transplant-related morbiditiesand may be considered an adverse prognostic factor for allogeneichematopoietic stem cell transplant recipients