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• W301314180 abstract "Allogeneic cell therapy, or donor lymphocyte infusion (DLI), following allogeneic bone marrow or blood stem cell transplantation (BMT) introduced at Hadassah in Jerusalem in early 1987 was already shown to be effective for treatment and prevention of relapse following maximally tolerated doses of chemoradiotherapy (1–3). Starting more than 5 years ago, these observations led to developing the concept of non-myeloablative stem cell transplantation (NST) as a new modality for the treatment of hematologic malignancies and more recently, metastatic solid tumors based on the use of alloreactive donor lymphocytes, rather than more aggressive chemoradiotherapy, for elimination of tumor cells resistant to conventional anti-cancer modalities (4-8). Optimal use of NST depends on induction of transplantation tolerance to donor alloantigens, which can be accomplished by a ‘window of immunosuppression’, using well tolerated immunosuppresive rather than myeloablative conditioning, followed by donor stem cell infusion (step 1). The concept of using NST for induction of host vs graft transplantation tolerance through the induction of a transient stage of mixed chimerism was developed in the 70s, first in rodents conditioned with non-myeloablative total lymphoid irradiation (TLI) (9-11). Following induction of host vs graft tolerance by donor stem cells, donor T-cells present in the graft can induce effective graft versus leukaemia, graft versus lymphoma, graft versus myeloma, graft versus genetically abnormal stem cells or graft versus autoimmunity effects (step 2), which can eliminate residual stem cells of host origin (1-3). Graft vs tumor effects could be further amplified with DLI given on an outpatient basis, preferably as graded increments for safer control of graft vs host disease (GVHD), while eliminating residual hematopoietic cells of host origin (step 3) by in vivo and/or in vitro activation of donor cells with rIL-2 (3). By using NST in steps 1-3, engraftment appears consistent with eventual replacement of host with donor hematopoietic cells. Several versions of NST regimen are currently being examined in patients with hematologic malignancies and metastatic solid tumors (11-14). The following report summarises the results of NST at Hadassah in Jerusalem." @default.
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• W301314180 date "2001-01-01" @default.
• W301314180 modified "2023-10-18" @default.
• W301314180 title "Shifting Towards Better Immunotherapy Rather Than More Intensive Chemoradiotherapy Using a Non-Myeloablative Approach in Patients with Leukemia" @default.
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• W301314180 doi "https://doi.org/10.1007/978-3-642-18156-6_107" @default.
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