Non-myeloablative allogeneic stem cell transplantation focusing on immunotherapy of life-threatening malignant and non-malignant diseases

Allogeneic bone marrow transplantation (BMT) represents an important therap eutic tool for treatment of otherwise incurable malignant and non-malignant diseases. Until recently, myeloablative regimens were considered mandatory for eradication of all undesirable host-derived hematopoietic elements. Ou r preclinical and ongoing clinical studies indicated that much more effecti ve eradication of host immunohematopoietic system cells could be achieved b y adoptive allogeneic cell therapy with donor lymphocyte infusion (DLI) fol lowing BMT. Thus, eradication of blood cancer cells, especially in patients with CML can be frequently accomplished despite complete resistance of suc h tumor cells to maximally tolerated doses of chemoradiotherapy. Our cumula tive experience suggested that graft versus leukemia (GVL) effects might be a useful tool for eradication of otherwise resistant tumor cells of host o rigin. The latter working hypothesis suggested that effective BMT procedure s may be accomplished without lethal conditioning of the host, using new we ll tolerated non-myeloablative regimen, thus possibly minimizing immediate and late side effects related to myeloablative procedures considered until recently mandatory for conditioning of BMT recipients. Recent clinical data that will be presented suggests that safe non-myeloablative stem cell tran splantation (NST), with no major toxicity can replace the conventional BMT. Thus, NST may provide an option for cure for a large spectrum of clinical indications in children and elderly individuals without lower or upper age limit, while minimizing procedure-related toxicity and mortality. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.