Effects of extending the duration of postgrafting immunosuppression and substituting granulocyte-colony-stimulating factor-mobilized peripheral blood mononuclear cells for marrow in allogeneic engraftment in a nonmyeloablative canine transplantation model.
Stable mixed donor/host hematopoietic chimerism was uniformly achieved in dogs given 200 cGy total body irradiation (TBI) before and immunosuppression with mycophenolate mofetil (MMF) for 28 days and cyclosporine (CSP) for 35 days after transplantation of marrow from dog leukocyte antigen-identical littermates. When the TBI dose was lowered to 100 cGy, donor marrow engraftment in 6 dogs was only transient, lasting 3 to 12 weeks. In this study, we asked whether stable engraftment in this model could be achieved: (1) by substituting recombinant canine granulocyte-colony-stimulating factor-mobilized peripheral blood mononuclear cells (G-PBMCs) for marrow and (2) by extending CSP administration from 35 to 100 days. Eighteen dogs were given G-PBMC grafts and MMF for 28 days. Eight of the 18 dogs received CSP for 35 days and 10 for 100 days. We found that substituting G-PBMCs for marrow did not increase the incidence of stable allogeneic engraftment (P = .11). However, increasing the duration of posttransplantation immunosuppression with CSP from 35 to 100 days favorably influenced stable donor engraftment (P = .06).
Zaucha
J M
JM
Clinical Research Division, Fred Hutchinson Cancer Research Center Washington, Seattle 98109-1024, USA.
Yu
C
C
Zellmer
E
E
Takatu
A
A
Junghanss
C
C
Little
M T
MT
Storb
R
R
D000818:Animals; D016026:Bone Marrow Transplantation; D016572:Cyclosporine / Q000008:administration & dosage* / Q000627:therapeutic use; D004285:Dogs; D004334:Drug Administration Schedule; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006648:Histocompatibility; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D023421:Models, Animal; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011828:Radiation Chimera; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
D015395:Histocompatibility Antigens Class I; D007166:Immunosuppressive Agents; C039692:histocompatibility antigen DLA; D016179:Granulocyte Colony-Stimulating Factor; D016572:Cyclosporine; D009173:Mycophenolic Acid