What Role Is There for Antithymocyte Globulin in Allogeneic Nonmyeloablative Canine Hematopoietic Cell Transplantation?

Diaconescu, Razvan; Little, Marie-Térèse; Leisenring, Wendy; Yunusov, Murad; Hogan, William J.; Sorror, Mohamed L.; Baron, Frédéric; Storb, Rainer

We investigated whether pretransplantation immunosuppression with canine-specific rabbit antithymocyte globulin (ATG), combined with a suboptimal dose of 1 Gy of total body irradiation (TBI), would permit engraftment of canine dog leukocyte antigen-identical marrow. Cumulative ATG doses of 2 to 5 mg/kg produced a T-cell depletion of 1 log in the peripheral blood and 50% in the lymph nodes. Serum levels of ATG peaked on days 4 to 6 after initiation of therapy and became undetectable by day 13 as a result of canine antibody responses to ATG. ATG prolonged allogeneic skin graft survival to 14 days (n = 5), compared with 8 days in control dogs (P = .0003). Five dogs were given marrow transplants after ATG (3.5–5 mg/kg) and 1 Gy of TBI. Posttransplantation immunosuppression consisted of mycophenolate mofetil and cyclosporine. All dogs showed initial engraftment, with maximum donor chimerism levels of 25%. However, only 1 dog achieved sustained engraftment, and 4 rejected their grafts. The duration of engraftment ranged from 8 to ≥36 weeks (median, 11 weeks), and this is comparable to that in 6 historical controls not given ATG (range, 3–12 weeks; median, 10 weeks; P = .20). The total nucleated cell doses in the marrow grafts had the highest correlation coefficient with the duration of engraftment: 0.82 (P = .09). We concluded that administering ATG before an otherwise suboptimal conditioning dose of 1 Gy of TBI failed to secure uniform stable hematopoietic engraftment.