Methods for human allografting
A method of preparing a human recipient for a graft from a human which includes: inducing mixed chimerism in the recipient (e.g., by administering to the recipient irradiation or chemotherapy), administering thymic irradiation, administering an antibody that depletes T cells, administering donor hematopoietic progenitor cells to the recipient, and administering an immunosuppressant.
1. A method of administering to a human recipient a graft from a human, the method comprising:
administering to the recipient an amount of chemotherapy sufficient to allow the induction of mixed chimerism in the recipient, wherein the chemotherapy comprises administering to the recipient a chemotherapeutic agent which is an antineoplastic agent, an antimetabolite, or a radiomimetic agent;
administering to the recipient, an amount of thymic irradiation sufficient to kill or otherwise inactivate recipient thymocytes;
administering to the recipient, an antibody that depletes T cells;
administering to the recipient, donor hematopoietic progenitor cells, wherein the hematopoietic progenitor cells are enriched for CD34 + cells prior to the administering; implanting the graft into the recipient, wherein the graft is an organ graft selected from a heart, pancreas, liver, or kidney graft; and
administering to the recipient, a non-chronic course of an immunosuppressant.
2. The method of claim 1 , wherein the amount of thymic irradiation is 700 cGy.
3. The method of claim 1 , wherein the method further includes, prior to one or more administration of an antibody that depletes T cells, administering to the recipient a steroid.
4. The method of claim 1 , wherein the non-chronic course is a 35-day course of cyclosporine followed by 7 days of tapering and ending on day 42.
5. The method of claim 1 , further comprising performing a splenectomy on the recipient.
6. The method of claim 1 , wherein the antibody that depletes T cells is an anti-CD2 monoclonal antibody.
7. The method of claim 1 , further comprising administering to the recipient an anti-B cell antibody.
8. A method of administering to a human recipient a graft from a human, the method comprising:
administering to the recipient an amount of chemotherapy sufficient to allow the induction of mixed chimerism in the recipient, wherein the chemotherapy comprises administering to the recipient a chemotherapeutic agent which is an antineoplastic agent, an antimetabolite, or a radiomimetic agent;
administering to the recipient, an amount of thymic irradiation sufficient to kill or otherwise inactivate recipient thymocytes;
administering to the recipient, an antibody that depletes T cells, wherein the antibody that depletes T cells is an anti-CD2 monoclonal antibody;
administering to the recipient, donor hematopoietic progenitor cells, wherein the hematopoietic progenitor cells are enriched for CD34 + cells prior to the administering; implanting the graft into the recipient, wherein the graft is an organ graft selected from a heart, pancreas, liver, or kidney graft;
administering to the recipient an anti-B cell antibody; and
administering to the recipient, a non-chronic course of an immunosuppressant.
9. The method of claim 8 , wherein the amount of thymic irradiation is 700 cGy.
10. The method of claim 8 , wherein the anti-CD2 monoclonal antibody is administered on days −4, −3, −2, −1.
11. The method of claim 8 , wherein the method further includes, prior to one or more administration of an antibody that depletes T cells, administering to the recipient a steroid.
12. The method of claim 8 , wherein the non-chronic course is a 35-day course of cyclosporine followed by 7 days of tapering and ending on day 42.
13. The method of claim 8 , further comprising performing a splenectomy on the recipient.
14. A method of administering to a human recipient a graft from a human, the method comprising:
administering to the recipient an amount of chemotherapy sufficient to allow the induction of mixed chimerism in the recipient, wherein the chemotherapy comprises administering to the recipient a chemotherapeutic agent which is cyclophosphamide;
administering to the recipient, an amount of thymic irradiation sufficient to kill or otherwise inactivate recipient thymocytes;
administering to the recipient, an antibody that depletes T cells;
administering to the recipient, donor hematopoietic progenitor cells;
implanting the graft into the recipient, wherein the graft is an organ graft;
administering to the recipient an anti-B cell antibody; and
administering to the recipient, a non-chronic course of an immunosuppressant.
15. The method of claim 14 , wherein the amount of thymic irradiation is 700 cGy.
16. The method of claim 14 , wherein the antibody that depletes T cells is an anti-CD2 monoclonal antibody.
17. The method of claim 16 , wherein the anti-CD2 monoclonal antibody is administered on days −4, −3, −2, −1.
18. The method of claim 14 , wherein the method further includes, prior to one or more administration of an antibody that depletes T cells, administering to the recipient a steroid.
19. The method of claim 14 , wherein the non-chronic course is a 35-day course of cyclosporine followed by 7 days of tapering and ending on day 42.
20. The method of claim 14 , further comprising performing a splenectomy on the recipient.