Induction of mixed allogeneic chimerism for leukemia

Hybrid (C56BL/6 × DBA) (BDF1; H-2 b/H-2 d) mice bearing the P815 leukemia (H-2 d) were grafted with a (CBA × C57BL/6)F1 (CBF1; H-2 k/H-2 b) cell suspension, comprising bone marrow cells (BMC; 25 × 10 6/mouse) and spleen cells (SC; 55 × 10 6/mouse) on day −4, then treated with cyclophosphamide (200 mg/kg) on day −2 and finally grafted once more with CBF1 cells (25 × 10 6 BMC + 7 × 10 6 SC) on day 0. Allogeneic cell graftings performed in this way induced durable mixed hematopoietic chimerism and significantly prolonged the survival of recipients, compared with that of leukemia-bearers grafted with syngeneic cells. The results obtained raise the possibility of using allogeneic hematopoietic tissue transplantation in combination with non-lethal cytoreductive therapy to induce a long-lasting graft-vs-leukemia effect.