Hematopoietic stem cell engraftment
The present invention provides clinical evidence for a method of stem cell transplantation that facilitates engraftment and reconstitutes immunocompetence of the recipient without requiring myeloablative conditioning.
1. A method of hematopoietic stem cell engraftment in a human patient, the method comprising:
infusing said human with a human or humanized monoclonal antibody specific for CD117 at a dose of up to about 3 mg/kg;
allowing serum levels of the antibody specific for CD117 to drop to a level of less than about 500 ng/ml;
administering to the patient a cell composition enriched for CD34+ hematopoietic stem cells in a dose of at least about 3×105 CD34+ cells/kg;
wherein sustained levels of blood myeloid chimerism of at least about 1% donor type CD15+ cells is obtained.
2. The method of claim 1 , wherein the antibody specific for CD117 is AMG 191.
3. The method of claim 1 , wherein the dose of antibody is up to 0.3 mg/kg; and is delivered in a single dose.
4. The method of claim 1 , wherein the cell composition enriched for CD34+ hematopoietic stem cells is tandemly selected for CD34+CD9Q+ cells.
5. The method of claim 1 , wherein the cell composition enriched for CD34+ hematopoietic stem cells is single enriched for expression of CD34+ cells, and wherein the dose is at least about 5×106 CD34+ cells/kg and containing not more than about 3×104 CD3+ cells/kg.
6. The method of claim 1 wherein the cell composition enriched for CD34+ hematopoietic stem cells is HLA matched to the recipient.
7. The method of claim 1 wherein the cell composition enriched for CD34+ hematopoietic stem cells is haplotype identical to the recipient.
8. The method of claim 1 , wherein the serum levels of the antibody specific for CD117 are less than about 10 ng/ml before administering the cell composition enriched for CD34+ hematopoietic stem cells.
9. The method of claim 1 , wherein the serum levels of the antibody specific for CD117 are less than about 5 ng/ml before administering the cell composition enriched for CD34+ hematopoietic stem cells.
10. The method of claim 1 , wherein the patient severe combined immunodeficiency (SCID).
11. The method of claim 1 wherein the patient has myelodysplastic syndrome (MDS).
12. The method of claim 1 wherein the patient has acute myelogenous leukemia (AML).
13. The method of claim 12 , wherein the AML is secondary to MDS.
14. The method of claim 1 , wherein the engraftment is performed in the absence of myeloablative conditioning.
15. The method of claim 1 , wherein the engraftment is performed in the presence of non-myeloablative conditioning.
16. The method of claim 15 , wherein the non-myeloablative conditioning comprises administration of an effective regimen of total lymphoid irradiation and anti-thymocyte globulin prior to engraftment.
17. The method of claim 16 , wherein sustained levels of full hematopoietic chimerism is obtained.