Abstract
BackgroundTotal body irradiation (TBI) has been part of standard conditioning regimens before allogeneic stem cell transplantation for many years. Its effect on normal tissue in these patients has not been studied extensively.MethodWe studied the in vivo cytogenetic effects of TBI and high-dose chemotherapy on skin fibroblasts from 35 allogeneic stem cell transplantation (SCT) patients. Biopsies were obtained prospectively (n = 18 patients) before, 3 and 12 months after allogeneic SCT and retrospectively (n = 17 patients) 23–65 months after SCT for G-banded chromosome analysis.ResultsChromosomal aberrations were detected in 2/18 patients (11 %) before allogeneic SCT, in 12/13 patients (92 %) after 3 months, in all patients after 12 months and in all patients in the retrospective group after allogeneic SCT. The percentage of aberrant cells was significantly higher at all times after allogeneic SCT compared to baseline analysis. Reciprocal translocations were the most common aberrations, but all other types of stable, structural chromosomal aberrations were also observed. Clonal aberrations were observed, but only in three cases they were detected in independently cultured flasks. A tendency to non-random clustering throughout the genome was observed. The percentage of aberrant cells was not different between patients with and without secondary malignancies in this study group.ConclusionHigh-dose chemotherapy and TBI leads to severe chromosomal damage in skin fibroblasts of patients after SCT. Our long-term data suggest that this damage increases with time, possibly due to in vivo radiation-induced chromosomal instability.
Highlights
The most worrisome long-term side effect after successful allogeneic stem cell transplantation (SCT) (SCT) is the increased risk of secondary malignancies.These tumors develop several years after transplantation with rising incidence over time
Chromosomal aberrations were detected in 2/18 patients (11 %) before allogeneic SCT, in 12/13 patients (92 %) after 3 months, in all patients after 12 months and in all patients in the retrospective group after allogeneic SCT
The percentage of aberrant cells was significantly higher at all times after allogeneic SCT compared to baseline analysis
Summary
The most worrisome long-term side effect after successful allogeneic SCT (SCT) is the increased risk of secondary malignancies. These tumors develop several years after transplantation with rising incidence over time. Ionizing radiation has the capacity to induce chromosomal aberrations in a variety of human tissues. Sublethal genomic damage may induce repairing cellular mechanisms after various times of cell cycle arrest or propagation of genetic lesions, which could lead to malignant transformation [13]. Evidence has accumulated that DNA-damage occurs in directly irradiated cells, and in the progeny of the irradiated cells at delayed times after radiation exposure [13, 14]. Total body irradiation (TBI) has been part of standard conditioning regimens before allogeneic stem cell transplantation for many years. Its effect on normal tissue in these patients has not been studied extensively
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