Pediatric patients with recurrent brain tumors have a poor prognosis and limited therapeutic options. We investigated the use of high-dose chemotherapy with adoptive immunotherapy for recurrent brain tumors. Three pediatric patients with recurrent brain tumors received high-dose chemotherapy. This was followed by adoptive transfer of ex-vivo expanded T-cells. The T-cells were generated from peripheral blood after immunization with autologous cancer cells. The objectives of this study included (1) establishing the safety and feasibility of this potential treatment, (2) measuring changes in immune response after high-dose chemotherapy and adoptive immunotherapy, and (3) determining whether adoptive immunotherapy would be able to translate into a clinical response. Immune function was tested in all patients at the time of enrollment into the study. Humoral responses to recall antigens delayed-type hypersensitivity (DTH) were intact in all patients. After immunizing patients with autologous cancer cells, peripheral blood lymphocytes were harvested and activated with anti-CD3, expanded in-vitro, and infused post-autologous transplant. Patients received at least three doses of the vaccine, each consisting of an intradermal administration near a draining lymph node at biweekly intervals. Toxicity was limited and well tolerated in all patients. All three patients showed a tumor-specific immune response by serial imaging. Responses were durable at 16, 23, and 48 months, respectively.
Fetal liver transplantation was attempted in 7 patients with aplastic anemia. 4 of these patients showed a partial response as evidenced by decrease in blood transfusion requirements and increase in the peripheral blood counts and hematopoietic cells in the bone marrow. Bone marrow culture studies revealed evidence of a temporary mixed lymphoid chimerism (cases 1 and 3). While case 1 lived for 16 months, case 3 is surviving at 17 months. None of the patients showed apparent graft-versus-host disease. Increased incidence of infections was noticed. Possible causes for the same are discussed. 3 patients failed to respond. Fetal liver transplant may be of therapeutic value in management of aplastic anemia.
Elevated levels of circulating nucleic acids have been found in a variety of benign and malignant pathological conditions. The ability to detect and quantitate specific DNA, RNA and micro-RNA sequences in serum/ plasma has opened up the possibilities of non-invasive diagnosis and monitoring of diseases. Circulating nucleic acids have now been shown to be useful in other conditions, such as diabetes mellitus, stroke and myocardial infarction. Plasma DNA is already in use for fetal blood group typing in many countries. With the rapid development in molecular biology techniques the application of circulating nucleic acids in diagnostics especially in cancer and prenatal diagnosis is expected to be revolutionized.
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