Combined organ and hematopoietic cells for transplantation tolerance of grafts
Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to a recipient, where tolerance to the graft is established through development of a persistent mixed chimerism. An individual with persistent mixed chimerism, usually for a period of at least six months, is able to withdraw from the use of immunosuppressive drugs after a period of time sufficient to establish tolerance.
1. A cellular product for establishing mixed chimerism in a solid organ transplant recipient, the product comprising:
greater than 5×10 5 CD34 + cells/kg recipient weight; and
greater than 1×10 5 CD3 + cells/kg recipient weight,
wherein the cellular product is substantially devoid of platelets and red blood cells.
2. The cellular product of claim 1 , comprising at least about 4×10 6 CD34 + cells/kg recipient weight.
3. The cellular product of claim 1 , comprising at least about 1×10 6 CD3 + cells/kg recipient weight.
4. The cellular product of claim 1 , comprising at least about 4×10 6 CD34 + cells/kg recipient weight and about 1×10 6 CD3 + cells/kg recipient weight.
5. The cellular product of claim 1 , comprising at least about 4×10 6 CD34 + cells/kg recipient weight and at least about 1×10 6 CD3 + cells/kg recipient weight.
6. The cellular product of claim 1 , wherein the CD34 + cells and the CD3 + cells are provided in separate containers.
7. The cellular product of claim 1 , wherein the CD34 + cells and the CD3 + cells are provided as a mixture in a common container.
8. The cellular product of claim 1 , wherein the CD34 + cells and the CD3 + cells are HLA matched to an HLA type of the solid organ transplant recipient.
9. The cellular product of claim 1 , wherein the CD34 + cells and the CD3 + cells are HLA mismatched to an HLA type of the solid organ transplant recipient.
10. The cellular product of claim 1 , wherein CD34 + cells and the CD3 + cells are from a single apheresis product.
11. A cellular product for establishing mixed chimerism in a solid organ transplant recipient that is HLA matched to the solid organ transplant donor, the product comprising:
greater than 5×10 5 CD34 + solid organ transplant donor derived cells/kg recipient weight, wherein the solid organ transplant donor's CD34 + cells are of an HLA type that is matched to the solid organ transplant recipient's HLA type; and
a defined amount of about 1×10 6 CD3 + cells/kg recipient weight, wherein the solid organ transplant donor's CD3 + cells are of an HLA type that is matched to the solid organ transplant recipient's HLA type,
wherein the cellular product is substantially devoid of platelets and red blood cells.
12. The cellular product of claim 11 , wherein the CD34 + cells and the CD3 + cells are provided in separate containers.
13. The cellular product of claim 11 , wherein the CD34 + cells and the CD3 + cells are provided as a mixture in a common container.
14. The cellular product of claim 11 , wherein the CD34 + cells and the CD3 + cells are HLA matched to the solid organ transplant recipient at all six alleles of HLA-A, HLA-B, and HLA-DR.
15. The cellular product of claim 11 , wherein the CD34 + cells and the CD3 + cells are from a donor related to the solid organ transplant recipient.
16. The cellular product of claim 15 , wherein the CD34 + cells and the CD3 + cells are from a sibling of the solid organ transplant recipient.
17. The cellular product of claim 11 , wherein CD34 + cells and the CD3 + cells are from a single apheresis product.
18. The cellular product of claim 11 , wherein CD34 + cells and the CD3 + cells are from multiple apheresis products.
19. The cellular product of claim 11 , wherein the solid organ is selected from the group consisting of heart, intestine, liver, lung, pancreas, and kidney.
20. The cellular product of claim 19 , wherein the solid organ is kidney.
21. A cellular product for establishing mixed chimerism in a solid organ transplant recipient that is HLA mismatched from the solid organ transplant donor, the product comprising:
greater than 5×10 5 CD34 + solid organ transplant donor derived cells/kg recipient weight, wherein the solid organ transplant donor's CD34 + cells are of an HLA type that is mismatched to the solid organ transplant recipient's HLA type; and
greater than 4×10 7 CD3 + solid organ transplant donor derived cells/kg recipient weight, wherein the solid organ transplant donor's CD3 + cells are of an HLA type that is mismatched to the solid organ transplant recipient's HLA type,
wherein the cellular product is substantially devoid of platelets and red blood cells.
22. The cellular product of claim 21 , wherein the CD3 + cells are from about 4×10 7 to about 1×10 8 solid organ transplant donor derived cells/kg recipient weight.
23. The cellular product of claim 21 , wherein the CD3 + cells are greater than 1×10 8 solid organ transplant donor derived cells/kg recipient weight.
24. The cellular product of claim 21 , wherein the CD34 + cells and the CD3 + cells are provided in separate containers.
25. The cellular product of claim 21 , wherein the CD34 + cells and the CD3 + cells are HLA mismatched to the solid organ transplant recipient at least one of six alleles of HLA-A, HLA-B, and HLA-DR.
26. The cellular product of claim 21 , wherein the CD34 + cells and the CD3 + cells are HLA mismatched to the solid organ transplant recipient at all six HLA alleles.
27. The cellular product of claim 21 , wherein CD34 + cells and the CD3 + cells are from a single apheresis product.
28. The cellular product of claim 21 , wherein CD34 + cells and the CD3 + cells are from multiple apheresis products.
29. The cellular product of claim 21 , wherein the solid organ is selected from the group consisting of heart, intestine, liver, lung, pancreas, and kidney.
30. The cellular product of claim 29 , wherein the solid organ is kidney.