Effects of Intrabone Marrow-Bone Marrow Transplantation Plus Adult Thymus Transplantation on Survival of Mice Bearing Leukemia

摘要

We recently found that allogeneic intrabone marrow-bone marrow transplantation (IBM-BMT) plus adult thymus transplantation (ATT) from the same donor is effective in mice bearing solid tumors. In the current study, we examined the effects of this strategy on the survival of mice with leukemia. One week after intravenous injection of 1 x 10(6) leukemic cells (EL-4, H-2(b)) into 8-week-old B6 (H-2(b)) mice, the mice were 8 Gy irradiated and transplanted with 1 x 10(7) bone marrow cells (BMCs) from 8-week-old BALB/c mice (H-2(d)) by IBM-BMT with or without donor lymphocyte infusion (DLI) or ATT. All the mice without treatment died within 70 days after injection of EL-4. About 40% of those treated with IBM-BMT alone died within 100 days due to tumor relapse. In contrast, those treated with IBM-BMT + DLI or ATT showed the longest survival rate without relapse of leukemia. In addition, the former showed less graft versus host disease (GVHD) than the latter. The mice treated with IBM-BMT + AU also showed an intermediate percentage of effector memory (EM) and central memory (CM) cells between those treated with BMT alone and those treated with IBM-BMT + DLI. The numbers and functions of T cells increased in those treated with IBM-BMT + ATT with interleukin-2 and interferon-y production. These results suggest that IBM-BMT+ ATT is effective in the treatment of leukemia with strong graft versus leukemia without increased risk of GVHD.

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