Somatic cell mutation in pediatric patients undergoing allogeneic bone marrow transplantation

Abstract

In order to examine whether bone marrow transplantation (BMT) has genotoxic effects in vivo, mutant frequencies (Mfs) at the hypoxanthine-guanine phosphoribosyl transferase (Hprt) locus were evaluated. Thirty-seven pediatric patients who had received allogeneic BMT for various hematologic or immunologic disorders were enrolled. Nine out of the 37 patients (24.3%) were found to have Hprt-Mfs exceeding the 99% confidence limits calculated from observation of healthy controls. Among factors including gender, primary disease of the patient, donor-recipient histocompatibility relationship, age of donor, and total body irradiation as conditioning regimen, none was associated with an increased Hprt-Mf. In three patients who had chimerism in their peripheral blood after BMT, Hprt mutant clones turned out to be of donor- or recipient-origin. Mfs at the T-cell receptor (TCR) locus were examined in 28 patients. Four patients (14.3%) were found to have increased TCR-Mfs. However, there were not any patients who showed elevation of both Hprt-and TCR-Mfs. These data, taken together, suggest that BMT may cause genotoxicity in vivo in some patients.