Successful adoptive immunotherapy of minimal residual disease after chemoradiotherapy and transplantation of bone marrow purged of leukaemia with mafosfamide

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Abstract
The effectiveness of adoptive immunotherapy in eliminating minimal residual disease in tumour-bearing mice after bone marrow transplantation was tested. This model mimics the human clinical condition when autologous bone marrow was purged ex vivo of leukaemia with mafosfamide or was not purged, and stored in liquid nitrogen before transplantation. Animals with minimal residual disease were prepared with marrow-ablative but leukaemia-noncurative doses of cyclophosphamide (CY) and total body irradiation followed by bone marrow transplantation. The next day after transplantation the recipients were injected with splenocytes immunized against the leukaemia cells (Imm-SPL) or monoclonal antibody (mAb). All the control mice died from leukaemia relapse, but 51% of purged bone marrow recipients, which received Imm-SPL, were cured. In similar conditions mAb did not exert a therapeutic effect. Imm-SPL were not able to eradicate minimal residual disease in the recipients of nonpurged bone marrow. Thus, in an animal model, we demonstrated that purging of bone marrow before grafting seems to be indispensable for successful adoptive immunotherapy of minimal residual disease (MRD) after autologous bone marrow transplantation.