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Low Radiation Dose and Low Cell Dose Increase the Risk of Graft Rejection in a Canine Hematopoietic Stem Cell Transplantation Model.
Biol Blood Marrow Transplant. 2016 Apr; 22(4):637-643.BB

Abstract

The canine hematopoietic stem cell transplantation (HSCT) model has become accepted in recent decades as a good preclinical model for the development of new transplantation strategies. Information on factors associated with outcome after allogeneic HSCT are a prerequisite for designing new risk-adapted transplantation protocols. Here we report a retrospective analysis aimed at identifying risk factors for allograft rejection in the canine HSCT model. A total of 75 dog leukocyte antigen-identical sibling HSCTs were performed since 2003 on 10 different protocols. Conditioning consisted of total body irradiation at 1.0 Gy (n = 20), 2.0 Gy (n = 40), or 4.5 Gy (n = 15). Bone marrow was infused either intravenously (n = 54) or intraosseously (n = 21). Cyclosporin A alone or different combinations of cyclosporine A, mycophenolate mofetil, and everolimus were used for immunosuppression. A median cell dose of 3.5 (range, 1.0 to 11.8) total nucleated cells (TNCs)/kg was infused. Cox analyses were used to assess the influence of age, weight, radiation dose, donor/recipient sex, type of immunosuppression, and cell dose (TNCs, CD34(+) cells) on allograft rejection. Initial engraftment occurred in all dogs. Forty-two dogs (56%) experienced graft rejection at median of 11 weeks (range, 6 to 56 weeks) after HSCT. Univariate analyses revealed radiation dose, type of immunosuppression, TNC dose, recipient weight, and recipient age as factors influencing long-term engraftment. In multivariate analysis, low radiation dose (P < .001) and low TNC cell count (P = .044) were identified as significant independent risk factors for graft rejection. Peripheral blood mononuclear cell chimerism ≥30% (P = .008) and granulocyte chimerism ≥70% (P = .023) at 4 weeks after HSCT were independent predictors of stable engraftment. In summary, these data indicate that even in low-dose total body irradiation-based regimens, the irradiation dose is important for engraftment. The level of blood chimerism at 4 weeks post-HSCT was predictive of long-term engraftment in the canine HSCT model.

Authors+Show Affiliations

Department of Medicine III, Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany. Electronic address: sandra.lange@med.uni-rostock.de.Department of Medicine III, Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.Institute for Biostatistics and Informatics in Medicine and Aging Research, Rostock University Medical Center, Rostock, Germany.Department of Medicine III, Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.Department of Medicine III, Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.Department of Medicine III, Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.Department of Medicine III, Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.Department of Medicine III, Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany; Small Animal Clinic, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.Department of Medicine III, Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.Department of Medicine III, Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26802322

Citation

Lange, Sandra, et al. "Low Radiation Dose and Low Cell Dose Increase the Risk of Graft Rejection in a Canine Hematopoietic Stem Cell Transplantation Model." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 22, no. 4, 2016, pp. 637-643.
Lange S, Steder A, Glass Ä, et al. Low Radiation Dose and Low Cell Dose Increase the Risk of Graft Rejection in a Canine Hematopoietic Stem Cell Transplantation Model. Biol Blood Marrow Transplant. 2016;22(4):637-643.
Lange, S., Steder, A., Glass, Ä., Killian, D., Wittmann, S., Machka, C., Werner, J., Schäfer, S., Roolf, C., & Junghanss, C. (2016). Low Radiation Dose and Low Cell Dose Increase the Risk of Graft Rejection in a Canine Hematopoietic Stem Cell Transplantation Model. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 22(4), 637-643. https://doi.org/10.1016/j.bbmt.2016.01.021
Lange S, et al. Low Radiation Dose and Low Cell Dose Increase the Risk of Graft Rejection in a Canine Hematopoietic Stem Cell Transplantation Model. Biol Blood Marrow Transplant. 2016;22(4):637-643. PubMed PMID: 26802322.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Low Radiation Dose and Low Cell Dose Increase the Risk of Graft Rejection in a Canine Hematopoietic Stem Cell Transplantation Model. AU - Lange,Sandra, AU - Steder,Anne, AU - Glass,Änne, AU - Killian,Doreen, AU - Wittmann,Susanne, AU - Machka,Christoph, AU - Werner,Juliane, AU - Schäfer,Stephanie, AU - Roolf,Catrin, AU - Junghanss,Christian, Y1 - 2016/01/21/ PY - 2015/10/28/received PY - 2016/01/11/accepted PY - 2016/1/24/entrez PY - 2016/1/24/pubmed PY - 2016/12/15/medline KW - Allogeneic hematopoietic stem cell transplantation KW - Chimerism KW - Dog KW - Graft rejection KW - Low-dose irradiation KW - Nonmyeloablative SP - 637 EP - 643 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol. Blood Marrow Transplant. VL - 22 IS - 4 N2 - The canine hematopoietic stem cell transplantation (HSCT) model has become accepted in recent decades as a good preclinical model for the development of new transplantation strategies. Information on factors associated with outcome after allogeneic HSCT are a prerequisite for designing new risk-adapted transplantation protocols. Here we report a retrospective analysis aimed at identifying risk factors for allograft rejection in the canine HSCT model. A total of 75 dog leukocyte antigen-identical sibling HSCTs were performed since 2003 on 10 different protocols. Conditioning consisted of total body irradiation at 1.0 Gy (n = 20), 2.0 Gy (n = 40), or 4.5 Gy (n = 15). Bone marrow was infused either intravenously (n = 54) or intraosseously (n = 21). Cyclosporin A alone or different combinations of cyclosporine A, mycophenolate mofetil, and everolimus were used for immunosuppression. A median cell dose of 3.5 (range, 1.0 to 11.8) total nucleated cells (TNCs)/kg was infused. Cox analyses were used to assess the influence of age, weight, radiation dose, donor/recipient sex, type of immunosuppression, and cell dose (TNCs, CD34(+) cells) on allograft rejection. Initial engraftment occurred in all dogs. Forty-two dogs (56%) experienced graft rejection at median of 11 weeks (range, 6 to 56 weeks) after HSCT. Univariate analyses revealed radiation dose, type of immunosuppression, TNC dose, recipient weight, and recipient age as factors influencing long-term engraftment. In multivariate analysis, low radiation dose (P < .001) and low TNC cell count (P = .044) were identified as significant independent risk factors for graft rejection. Peripheral blood mononuclear cell chimerism ≥30% (P = .008) and granulocyte chimerism ≥70% (P = .023) at 4 weeks after HSCT were independent predictors of stable engraftment. In summary, these data indicate that even in low-dose total body irradiation-based regimens, the irradiation dose is important for engraftment. The level of blood chimerism at 4 weeks post-HSCT was predictive of long-term engraftment in the canine HSCT model. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/26802322/Low_Radiation_Dose_and_Low_Cell_Dose_Increase_the_Risk_of_Graft_Rejection_in_a_Canine_Hematopoietic_Stem_Cell_Transplantation_Model_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(16)00087-2 DB - PRIME DP - Unbound Medicine ER -