Severe canine hereditary hemolytic anemia treated by nonmyeloablative marrow transplantation

Severe hemolytic anemia in Basenji dogs secondary to pyruvate kinase (PK) d eficiency can be corrected by marrow allografts from healthy littermates af ter a conventional high-dose myeloablative conditioning regimen. The nonmye loablative conditioning regimen used here, which consisted of a sublethal d ose of 200 cGy total body irradiation before and immunosuppression with myc ophenolate mofetil and cyclosporine after a dog leukocyte antigen DLA)ident ical littermate allograft, has been found to be effective in establishing s table mixed donor/host hematopoietic chimerism in normal dogs. We explored the feasibility of nonmyeloablative marrow allografts for the treatment of canine PK deficiency and studied the effect of stable allogeneic mixed hema topoietic chimerism on the natural course of the disease. Five affected dog s received transplants, of which 3 dogs had advanced liver cirrhosis and my elofibrosis. Both complications were presumed to be due to iron overload. A ll 5 dogs showed initial engraftment. Two rejected their grafts after 6 wee ks but survived with complete autologous marrow recovery and return of the disease, One dog died from liver failure on day 27 with 60% donor engraftme nt, Two dogs have shown sustained mixed donor/host chimerism for more than a year with 85% and 12% donor hematopoietic cells, respectively. Overall cl inical response correlated with the degree of donor chimerism, The dog with the low degree of chimerism achieved partial resolution of hemolysis, but the disease symptoms persisted as manifested by increasing iron overload re sulting in progression of marrow and liver fibrosis, The dog with the high degree of donor chimerism achieved almost complete resolution of hemolysis with a decrease of marrow iron content and resolution of marrow fibrosis, T hese observations suggest that mixed hematopoietic chimerism can be relativ ely safely established in dogs with PK deficiency even in the presence of a dvanced liver cirrhosis, However, although effective in correcting or delay ing the development of myelofibrosis, a low degree of mixed chimerism was n ot sufficient to prevent continued hemolysis of red blood cells of host ori gin. Complete donor chimerism appears necessary to achieve a long-term cure .