Postgrafting immunosuppression with sirolimus and cyclosporine facilitates stable mixed hematopoietic chimerism in dogs given sublethal total body irradiation.

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Postgrafting immunosuppression with sirolimus and cyclosporine facilitates stable mixed hematopoietic chimerism in dogs given sublethal total body irradiation before marrow transplantation from DLA-identical littermates William J Hogan, Marie-Térèse Little, Eustacia Zellmer, Anke Friedetzky, Razvan Diaconescu, Serina Gisburne, Richard Lee, Christian Kuhr, Rainer Storb Biology of Blood and Marrow Transplantation Volume 9, Issue 8, Pages 489-495 (August 2003) DOI: 10.1016/S1083-8791(03)00148-4

Figure 1 In vitro proliferation of 2 primary canine T-cell preparations stimulated with 4 μg/mL PHA-M. Cells were pulsed for 16 hours with tritiated thymidine (3HTd-R) after 48 hours of culture with 0–100 nmol/L of SRL. The proliferation of the T-cell preparations was suppressed by 80% and 60%, respectively. Maximal inhibition occurred at concentrations as low as 6 nmol/L SRL, demonstrating potent antiproliferative effects on canine T cells. Biology of Blood and Marrow Transplantation 2003 9, 489-495DOI: (10.1016/S1083-8791(03)00148-4)

Figure 2 Cohort 1 (2 Gy TBI): Chimerism and hematologic values. Percent donor peripheral blood granulocytes (A) and lymphocytes (B) after transplantation in 7 dogs given 200 cGy TBI and DLA-identical marrow grafts. Results were estimated by visual approximation of (CA)n dinucleotide repeat marker results. Median hematologic values for 7 dogs (C). Biology of Blood and Marrow Transplantation 2003 9, 489-495DOI: (10.1016/S1083-8791(03)00148-4)

Figure 3 Cohort 2 (1 Gy TBI): Chimerism and hematologic values. Percent donor peripheral blood granulocytes (A) and lymphocytes (B) after transplantation in 5 dogs given 100 cGy TBI and DLA-identical marrow grafts. Results were estimated by visual approximation of (CA)n dinucleotide repeat marker results. Median hematologic values for 5 dogs (C). Biology of Blood and Marrow Transplantation 2003 9, 489-495DOI: (10.1016/S1083-8791(03)00148-4)

Figure 4 Comparison of dose intensity and drug levels for CSP (n = 12) (A) and SRL (n = 8) (B). Median doses of CSP and SRL are represented by bars, with corresponding units on the left vertical axis, whereas median values for CSP or SRL serum levels are plotted as points with corresponding units on the right vertical axis. Biology of Blood and Marrow Transplantation 2003 9, 489-495DOI: (10.1016/S1083-8791(03)00148-4)

Figure 5 Liver function tests in dogs from both cohorts (n = 12). A, Bilirubin. B, Aspartate transaminase (AST). C, Alkaline phosphatase. One dog (E912) developed transient jaundice, possibly as a result of hemolysis, (maximum total bilirubin, 4.2; direct, 2.5 mg/dL), which resolved within 2 days (total bilirubin, 0.6 mg/dL). The animal recovered completely and has stable engraftment more than 1 year later. Biology of Blood and Marrow Transplantation 2003 9, 489-495DOI: (10.1016/S1083-8791(03)00148-4)