Irradiation of Donor Mononuclear Cells for Treatment of Chemorefractory Metastatic Solid Cancers: A Community-Based Immune Transplant Pilot Study
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Purpose Chemotherapy has demonstrated ability to generate tumor antigens secondary to induction of apoptosis, against which human leukocyte antigen-compatible, irradiated, related donor mononuclear cells may be administered with immune stimulation to activate antigen presenting and cytotoxic T cells, while minimizing risk of graft-versus-host disease (GVHD). The present study endeavours to describe feasibility and efficacy of this treatment, specifically in the community setting. Materials and Methods Eligible patients had rapidly progressive, chemorefractory metastatic solid tumors. Treatment consisted of intravenous etoposide and cyclosporine for three days followed by granulocytemacrophage colony-stimulating factor for 5 days. The following week, 5×107 haploidentical or more closely matched irradiated donor mononuclear cells were given weekly for 10 weeks along with interleukin-2. Results Three patients were enrolled, and the regimen was well-tolerated, with no GVHD observed. All patients had clinical response, despite advanced and heavily pretreated disease. Conclusion The above-outlined protocol demonstrates favorable tolerability and efficacy, and appears to be feasible in the community setting. While the optimal chemotherapy, immunostimulation, and irradiation regimens may be further optimized, future investigation appears warranted, and may include community oncology programs.
Abstract
Purpose Chemotherapy has demonstrated ability to generate tumor antigens secondary to induction of apoptosis, against which human leukocyte antigen-compatible, irradiated, related donor mononuclear cells may be administered with immune stimulation to activate antigen presenting and cytotoxic T cells, while minimizing risk of graft-versus-host disease (GVHD). The present study endeavours to describe feasibility and efficacy of this treatment, specifically in the community setting. Materials and Methods Eligible patients had rapidly progressive, chemorefractory metastatic solid tumors. Treatment consisted of intravenous etoposide and cyclosporine for three days followed by granulocytemacrophage colony-stimulating factor for 5 days. The following week, 5×107 haploidentical or more closely matched irradiated donor mononuclear cells were given weekly for 10 weeks along with interleukin-2. Results Three patients were enrolled, and the regimen was well-tolerated, with no GVHD observed. All patients had clinical response, despite advanced and heavily pretreated disease. Conclusion The above-outlined protocol demonstrates favorable tolerability and efficacy, and appears to be feasible in the community setting. While the optimal chemotherapy, immunostimulation, and irradiation regimens may be further optimized, future investigation appears warranted, and may include community oncology programs.
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