Preliminary data summarized in the present article provides support to a new treatment strategy based on cell-mediated immunotherapy of patients with multi-drug-resistant hematologic malignancies, based on a 2-step cell-mediated immunotherapy approach. First, attempting to induce a stage of minimal residual disease or minimizing tumor burden by conventional modalities, which can usually be accomplished at an early stage of the disease. Next, apply innovative cell-mediated immunotherapy by mismatched pre-activated killer cells following mild immunosuppressive conditioning. Out of a total of 33 patients with different drug-resistant hematologic malignancies, 23 accomplished complete remission and 6 observed for more than 5 years with no further treatment are probably cured. Using pre-activated mismatched killer cells was based on short-term circulation of multi-potent cancer killer cells including a mixture of T, NK & NKT cells, could result in most effective cytoreduction of all drug-resistant malignant cells, possibly even accomplishing cure, with no need for allogeneic stem cell transplantation, thus avoiding the hazardous risks of acute and chronic graft-vs-host disease. Our working hypothesis supported by pre-clinical and preliminary clinical investigations confirms the feasibility to cure patients with different hematologic malignancies considered otherwise incurable using mismatched pre-activated killer cells following mild immunosuppressive conditioning. Our suggestion that our innovative cell-mediated immunotherapy could eliminate fully resistant malignant cells in patients with a broad range of otherwise incurable hematologic malignancies needs to be confirmed by prospective randomized clinical trials.
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