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 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 çellfree DNA seem to be associated with transplant-related morbidities and may be considered an adverse prognostic factor for allogeneic hematopoietic stem cell transplant recipients.

Two Different Transplant Preconditioning Regimens Combined with Irradiation and Chemotherapy in the Treatment of Childhood Leukemia: Systematic Review and Meta-Analysis

“…Hematopoietic stem cell transplantation can cure childhood leukemia, aplastic anemia, hemoglobin disease, and congenital immune deficiency [ 28 ]. The pretreatment regiments for pediatric transplantation include total body irradiation (TBI) and chemotherapy alone [ 29 – 32 ]. The most classical pretreatment regiments are TBI/CY and BU/CY.…”

Liquid biopsies and minimal residual disease in lymphoid malignancies

“…Another study on pediatric ALL looked into the level of clonal Ig/TCR gene rearrangements in plasma and compared it to MRD determined by flow cytometry in BM. The authors came to the conclusion that both approaches could independently predict relapse despite the methods’ poor correlation ( 49 ). All these studies have shown that MRD monitoring of the PB appears to be an adequate alternative to frequent BM aspirations, however, additional studies investigating the biology of liquid biopsies in ALL and its potential as an MRD marker in larger patient cohorts within current treatment protocols are warranted.…”

The Minimal Residual Disease Using Liquid Biopsies in Hematological Malignancies

“…They did not show a correlation, but the peripheral blood could predict a relapse [ 87 ]. Another study showed that BCR/ABL1 -positive ALL patients had lower pre-transplant cfDNA levels than BCR/ABL1 -negative ALL patients [ 88 ]. More studies are needed to use cfDNA for monitoring the MRD in ALL.…”