Effectiveness of allogeneic NK cells in haploidentical bone marrow transplantation for leukemic mice.

The aim of study was to investigate the effectiveness of allogeneic natural killer (NK) cells in haploidentical bone marrow transplantation (BMT) for leukemia mice. CB6F(1)(H-2b/d) murine model of EL9611 (H-2d) erythroleukemia was established by intravenous injection of EL9611 (H-2(d)) cells. CB6F(1)(H-2b/d) mice were transplanted with bone marrow (BM) cells from C57BL/6(H-2b) mice. Seventy CB6F(1)(H-2b/d) mice were randomly divided into 7 groups with 10 mice per group. 5 control groups were: group 1, in which no treatment was performed; group 2, in which mice were lethally irradiated (9 Gy); group 3, in which mice were treated with cytarabine with dose of 50 mg/kg for 6 days followed by the infusion of EL9611 (H-2(d)); group 4, in which mice were transplanted with BMT and group 5-the GVHD-control group, in which mice were transplanted with BM and spleen cells from C57BL/6(H-2b) mice 4 hours after irradiation. Experimental groups were divided into 2 groups: group A, in which mice were injected with C57BL/6(H-2b) NK cells (1 x 10(6)) after irradiation and were transplanted with BM from C57BL/6(H-2b) 4 hours later, and group B, in which mice were transplanted with BM cells and spleen cells from C57BL/6(H-2b) 4 hours after irradiation. The effect was assessed and compared by blood picture, survival time, body weight, and histopathology in the recipients. The results showed that the survival times in control group 1, 2, 3 and 5 were (10.10 +/- 0.88), (9.80 +/- 0.92), (22.70 +/- 3.23) and (20.10 +/- 1.73) days respectively. The survival time of control group 4 was (30.10 +/- 15.95) days and was over 30 days in 2 mice. The survival times in experimental group A and B were (39.10 +/- 18.11) and (49.30 +/- 17.24) days respectively. 4 mice in experimental group 1 and 7 mice in group 2 survived over 30 days. The survival time of experimental group 1 was significantly longer than that of control group 1, 2, 3 and 5 (p < 0.01). The survival time of experimental group 2 was significantly longer than that of other groups (p < 0.05). Histopathologic examination showed that splenohepatomegalia and disorganization of liver and spleen with infiltration of a large amount of leukemia cells in mice dead of leukemia. Chimerism of Y chromosome was shown in mice of experimental groups with long survival time. It is concluded that the injection with donor-derived NK cells can both eliminate leukemia cells and decrease the severity of GVHD after haploidential BMT.