Induction of mixed allogeneic chimerism for leukemia

Hybrid (C56BL/6 x DBA) (BDF1; H-2(b)/H-2(d)) mice bearing the P815 leukemia (H-2(d)) were grafted with a (CBA x C57BL/6)F1 (CBF1; H-2(k)/H-2(b)) cell suspension, comprising bone marrow cells (BMC; 25 x 10(6)/mouse) and spleen cells (SC; 55 x 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 x 10(6) BMC+7 x 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. (C) 1997 Elsevier Science Ltd.