Jesus Duque-Afonso1, Miguel Waterhouse2, Dietmar Pfeifer3, Marie Follo4, Justus Duyster1, Hartmut Bertz1, Jürgen Finke1. 1. Department of Hematology, Oncology and Stem Cell Transplantation, University of Freiburg, Faculty of Medicine, Freiburg, Germany. 2. Department of Hematology, Oncology and Stem Cell Transplantation, University of Freiburg, Faculty of Medicine, Freiburg, Germany; Genomics Core Facility, Department of Hematology, Oncology and Stem cell Transplantation, University of Freiburg, Faculty of Medicine, Freiburg, Germany. Electronic address: miguel.waterhouse@uniklinik-freiburg.de. 3. Department of Hematology, Oncology and Stem Cell Transplantation, University of Freiburg, Faculty of Medicine, Freiburg, Germany; Genomics Core Facility, Department of Hematology, Oncology and Stem cell Transplantation, University of Freiburg, Faculty of Medicine, Freiburg, Germany. 4. Department of Hematology, Oncology and Stem Cell Transplantation, University of Freiburg, Faculty of Medicine, Freiburg, Germany; Lighthouse Core Facility. Department of Hematology, Oncology and Stem cell Transplantation, University of Freiburg, Faculty of Medicine, Freiburg, Germany.
Abstract
Cell-free DNA (cfDNA) isolated from plasma or serum has received increasing interest for diagnostic applications in pregnancy, solid tumors and solid organ transplantation. The reported clinical usefulness of cfDNA obtained from plasma or serum in patients undergoing allogeneic cell transplantation (alloHSCT) is scarce. OBJECTIVE: To analyze the potential clinical utility of cfDNA chimerism analysis after alloHSCT. DESIGN AND METHODS: A total of 196 samples obtained from 110 patients were investigated for their chimeric status both in peripheral blood and plasma using standard PCR for microsatellite amplification. Plasma DNA size distribution was analyzed using capillary electrophoresis. RESULTS: The mean cfDNA concentration in the transplanted patients was 469ng/ml (range: 50-10,700ng/ml). The size range of almost 80% of the analyzed fragments was between 80 and 200bp. In 41 out of the 110 patients included in the study a mixture of donor and recipient plasma cfDNA was detected. There was a statistically significant difference in the percentage of plasma mixed chimerism between the patients without transplant related complications and the patients with either GvHD (p<0.05) or relapse (p<0.01). In those patients who showed improvement of GvHD also displayed a decrease in the observable percentage of recipient cfDNA during GvHD treatment. In patients without improvement or even with worsening of acute GvHD, stable or increasing levels of recipient cfDNA were detected. CONCLUSIONS: cfDNA in combination with peripheral blood and bone marrow cell chimerism analysis might improve its utility in the clinic in particular in those patients with clinical complications after alloHSCT.
Cell-free DNA (cfDNA) isolated from plasma or serum has received increasing interest for diagnostic applications in pregnancy, solid tumors and solid organ transplantation. The reported clinical usefulness of cfDNA obtained from plasma or serum in patients undergoing allogeneic cell transplantation (alloHSCT) is scarce. OBJECTIVE: To analyze the potential clinical utility of cfDNA chimerism analysis after alloHSCT. DESIGN AND METHODS: A total of 196 samples obtained from 110 patients were investigated for their chimeric status both in peripheral blood and plasma using standard PCR for microsatellite amplification. Plasma DNA size distribution was analyzed using capillary electrophoresis. RESULTS: The mean cfDNA concentration in the transplanted patients was 469ng/ml (range: 50-10,700ng/ml). The size range of almost 80% of the analyzed fragments was between 80 and 200bp. In 41 out of the 110 patients included in the study a mixture of donor and recipient plasma cfDNA was detected. There was a statistically significant difference in the percentage of plasma mixed chimerism between the patients without transplant related complications and the patients with either GvHD (p<0.05) or relapse (p<0.01). In those patients who showed improvement of GvHD also displayed a decrease in the observable percentage of recipient cfDNA during GvHD treatment. In patients without improvement or even with worsening of acute GvHD, stable or increasing levels of recipient cfDNA were detected. CONCLUSIONS: cfDNA in combination with peripheral blood and bone marrow cell chimerism analysis might improve its utility in the clinic in particular in those patients with clinical complications after alloHSCT.
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