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The prognostic significance of minimal residual disease in the early phases of chemotherapy in dogs with high-grade B-cell lymphoma
Authors:Masahiko Sato  Jumpei Yamzaki  Yuko Goto-Koshino  Masashi Takahashi  Yasuhito Fujino  Koichi Ohno  Hajime Tsujimoto
Institution:1. Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, 3584 CM Utrecht, The Netherlands;2. Department of Pathobiology, Division Pathology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands;3. Department of Pathology, Leiden University Medical Centre, Albinusdreef 2, 2300 RC Leiden, The Netherlands;1. Laboratory of Veterinary Surgery, Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan;2. Department of Medical Genome Science, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa 277-8561, Japan
Abstract:The prognostic significance of minimal residual disease (MRD) in the early phases of chemotherapy was examined in 36 dogs with multicentric high-grade B-cell lymphoma. Sequences of immunoglobulin heavy chain (IgH) gene fragments from lymphoma cells were amplified and used to design allele-specific primers and probes for real-time PCR. The dogs were treated with a 6-month modified version of the University of Wisconsin–Madison chemotherapy protocol (UW-25) and evaluated for the MRD level at weeks 6 and 11 of UW-25.Of the 31 dogs that remained on the protocol at week 11, 14 were found to be MRD negative (<10 tumour cells/105 peripheral blood mononuclear cells PBMCs]), whereas the other 17 were MRD positive (?10 tumour cells/105 PBMCs). The progression-free survival of the dogs with MRD-negative status at week 11 (median, 337 days) was significantly longer than that of the MRD-positive dogs at the same time point (median, 196 days) (P = 0.0002). These results indicate the clinical significance of MRD as a prognostic marker in the early phase of chemotherapy.
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