Allogeneic bone marrow transplantation with reduced conditioning (RC-BMT)

Allogeneic bone marrow transplantation with conventional conditioning (CC-BMT) has the potential of curing various malignant and non-malignant diseases. The curative mechanisms encompass 1) stem cell support for myeloablative radio-chemotherapy, 2) the graft-versus-tumor (GVT) effect, 3) gene replacement for genetic diseases and 4) immunoablation for autoimmune diseases. CC-BMT is characterized by high intensity conditioning, the requirement of prolonged and expensive hospital treatment and a treatment related mortality (TRM) of 10-50% depending on diagnosis, disease stage, patient age and donor type. Recent preclinical and clinical progress has resulted in the emergence of new concepts and procedures that allow replacement of patient bone marrow and immune system with that of the donor by a transplant procedure with markedly reduced conditioning (RC-BMT). This type of transplant, sometimes referred to as mini-BMT, activates curative mechanisms 2-4, which for a number of diseases seems sufficient for cure. It avoids the severe organ toxicity of myeloablative radio-chemotherapy and the complications of profound neutropenia. Patients beyond the age limit of conventional BMT (50-60 yr) may therefore be candidates for this type of transplant as well as patients which because of other medical conditions or the type of disease for which the transplant is needed are poor candidates for CC-BMT. The procedure can be performed in an outpatient setting. The resulting cost reduction should contribute to making allogenic BMT more readily available. This review describes basic concepts and procedures involved in RC-BMT and summarizes preliminary results obtained with RC-BMT in different transplant centers.