Absence of Damaging Effects of Stem Cell Donation in Unrelated Donors Assessed By FISH and Gene Variance Screening

Granulocyte-Colony-Stimulating factor (G-CSF) is currently the standard mobilizing agent for peripheral blood stem cell (PBSC) donation. While G-CSF use is associated with mild transient side-effects, concerns that it may trigger hematological malignancy were raised by a study of PBSC donors found to display epigenetic and genetic changes similar to those observed in leukemia patients. Although several studies have failed to reproduce the original data, possible long-term effects of G-CSF mobilization on chromosome integrity remain unclear. In the setting of a multi-center clinical trial we screened blood samples from PBSC donors for aberrations at cellular and gene level that are common in hematological malignancies using fluorescence in situ hybridization (FISH) and next generation sequencing (NGS) assays. Samples collected before, on the day of donation, 90 and 180 days after G-CSF admission confirmed the absence of short-term effects in 50 PBSC donors on both quiescent and dividing cells. The data obtained from interphase cells and chromosome preparations from 50 individuals tested 3 to 5 years after PBSC donation did not differ either from individuals post bone marrow (BM) donation over a similar time period or healthy persons. In an attempt to finally resolve the residual uncertainty surrounding the effects of the G-CSF administration we used next generation sequencing to search for cryptic genome aberrations that may remain undetected by FISH screening. The gene profile of samples from 47 PBSC donors assessed using a panel targeting 54 genes (TruSight Myeloid panel, Illumina) was found to be stable throughout the study period. These data conclusively demonstrate the absence of any detrimental effects on the genome integrity of lymphocytes caused by PBSC or BM donation.