Method for chemoselection
A method of radiation-free hematopoietic stem cell (HSC) transplantation comprises administering to a mammalian subject one or two doses of 2 to 10 mg/kg body weight of a purine base analog, such as 6TG as a pre-conditioning step. The method further comprises engrafting into the subject hypoxanthine-guanine phosphoribosyltransferase (HPRT)-deficient donor HSCs within 48 to 72 hours of the pre-conditioning step; and administering to the subject about 1 to 5 mg/kg of the purine base analog every two to four days for two to eight weeks following the engrafting step. The method is performed in the absence of pre-conditioning via radiation. The subject is therefore not treated with myeloablative radiation in preparation for transplantation, and thus the subject is free of myeloablative radiation-induced toxicity.
1. A method of radiation-free hematopoietic stem cell (HSC) transplantation, the method comprising:
(a) engrafting into a pre-conditioned mammalian subject hypoxanthine-guanine phosphoribosyltransferase (HPRT)-deficient donor HSCs; and
(b) immediately administering to the subject about 1 to 5 mg/kg of a purine base analog selected from 6-thioguanine (6TG), 6-mercaptopurine (6-MP), or azathiopurine (AZA) every two to four days for two to eight weeks;
wherein the method is performed in the absence of pre-conditioning via radiation.
2. The method of claim 1 , wherein the subject is human.
3. The method of claim 1 , wherein the subject has a hereditary or genetic disorder.
4. The method of claim 1 , wherein the subject has an acquired disease affecting lymphohematopoietic cells.
5. The method of claim 4 , wherein the disease is human immunodeficiency virus (HIV) infection or acquired immune deficiency syndrome (AIDS).
6. The method of claim 4 , wherein the disease is a lymphohematopoietic malignancy.
7. The method of claim 1 , wherein the subject has a disease or disorder of hematopoietic or thrombopoietic or lymphopoietic system.
8. The method of claim 7 , wherein the disease or disorder of the hematopoietic system is a hemoglobinopathy.
9. The method of claim 1 , wherein the method further comprises bone marrow transplantation.
10. The method of claim 1 , wherein the purine base analog is 6TG.
11. The method of claim 1 , wherein the total 6TG dosage administered to the subject in the administering of step (b) does not exceed 105 mg.
12. The method of claim 1 , wherein the total 6TG dosage administered to the subject in the administering of step (b) does not exceed 75 mg.
13. The method of claim 1 , wherein the administering of step (b) is performed every 3 days and for not more than four weeks following the engrafting step.
14. The method of claim 1 , wherein the transplanted HSCs are autologous or syngeneic.
15. The method of claim 1 , wherein the transplanted HSCs are allogeneic.
16. The method of claim 1 , wherein the subject is not treated with myeloablative radiation.
17. A method of treating symptoms of a disease or disorder in a mammalian subject, the method comprising:
(a) administering a pre-conditioning treatment to the subject;
(b) engrafting into the subject hypoxanthine-guanine phosphoribosyltransferase (HPRT)-deficient donor HSCs; and
(c) immediately administering to the subject about 1 to 5 mg/kg of a purine base analog selected from 6-thioguanine (6TG), 6-mercaptopurine (6-MP), or azathiopurine (AZA) every two to four days for two to eight weeks;
wherein the method is performed in the absence of pre-conditioning via radiation.
18. The method of claim 17 , wherein the subject has human immunodeficiency virus (HIV) infection or acquired immune deficiency syndrome (AIDS).
19. The method of claim 17 , wherein the subject has a lymphohematopoietic malignancy.
20. The method of claim 17 , wherein the subject has a disease or disorder of hematopoietic or thrombopoietic or lymphopoietic system.
21. The method of claim 20 , wherein the disease or disorder of the hematopoietic system is a hemoglobinopathy.
22. The method of claim 17 , wherein the method further comprises bone marrow or hematopoietic stem cell transplantation.
23. The method of claim 17 , wherein the subject is human.
24. The method of claim 17 , wherein the purine base analog is 6TG.
25. The method of claim 17 , wherein the administering of step (c) is performed every 3 days and for not more than four weeks following the engrafting step.
26. The method of claim 17 , wherein the transplanted HSCs are autologous or syngeneic.
27. The method of claim 17 , wherein the transplanted HSCs are allogeneic.
28. The method of claim 17 , wherein the subject is not treated with myeloablative radiation.