Combination therapy for a stable and long term engraftment

A method of reducing graft rejection and/or graft versus host disease (GVHD), the method comprising:

• (a) conditioning a subject under a reduced intensity conditioning, wherein said reduced intensity conditioning comprises a total body irradiation (TBI) or a total lymphoid irradiation (TLI) at an irradiation dose within the range of 0.5-5 Gy, and a chemotherapeutic agent;
• (b) transplanting into the subject a dose of T cell depleted immature hematopoietic cells obtained from a non-syngeneic donor, wherein said dose of said T cell depleted immature hematopoietic cells comprises less than 5×105 CD3+ T cells per kilogram body weight of the subject, and wherein said dose comprises at least 5×106 CD34+ cells per kilogram body weight of the subject;
• and subsequently
• (c) administering to the subject a therapeutically effective amount of cyclophosphamide, wherein said therapeutically effective amount comprises 25-200 mg cyclophosphamide per kilogram body weight of the subject, and wherein said cyclophosphamide is administered to the subject following transplantation, and wherein said subject is not treated with GVHD prophylaxis for more than 10 days post transplant,
• thereby reducing graft rejection and/or GVHD.

A method of inducing donor specific tolerance in a subject, the method comprising:

• (a) transplanting into a subject conditioned under reduced intensity conditioning, wherein said reduced intensity conditioning is a non-myeloablative conditioning comprising a total body irradiation (TBI) or a total lymphoid irradiation (TLI) at an irradiation dose within the range of 0.5-5 Gy, a dose of T cell depleted immature hematopoietic cells obtained from a non-syngeneic donor, wherein said dose of said T cell depleted immature hematopoietic cells comprises less than 5×105 CD3+ T cells per kilogram body weight of the subject, and wherein said dose comprises at least 5×106 CD34+ cells per kilogram body weight of the subject;
• and subsequently
• (b) administering to the subject a therapeutically effective amount of cyclophosphamide, wherein said therapeutically effective amount comprises 25-200 mg cyclophosphamide per kilogram body weight of the subject, and wherein said cyclophosphamide is administered to the subject following transplantation, and wherein said subject is not treated with GVHD prophylaxis for more than 10 days post transplant,
• thereby inducing donor specific tolerance in the subject.