Induction Of Mixed Haematopoietic Chimerism In Patients Using Fludarabine, Low Dose Total Body Irradiation, Peripheral Blood Stem Cell Infusion And Post-Transplant Immunosuppression With Cyclosporine And Mycophenolate Mofetil

It is planned to test the hypothesis that we can reliably establish mixed chimerism in humans using a non-myeloablative regimen and that we can decrease the incidence of graft rejection by the addition of 3 doses of fludarabine (30 mg/m2 given days -4, -3, -2) before 200 cGy TBI. Mixed chimerism will be defined as the detection of donor cells after transplant at > than 1% and <= 95% of the eripheral blood CD3+ cell population. Patients with low levels of T cell chimerism or those with continued evidence of malignancy (without GVHD) will be evaluated for the effects of DLI on conversion to full chimerism and for anti-tumour activity. The source of stem cells will be G-CSF mobilised PBSC from apheresis products collected on two consecutive days infused into the patient on day 0. Donor lymphocyte infusions may be given starting 2 months post-transplant in an attempt to convert mixed chimerism to full donor chimerism and to eradicate the malignancy. A graded series of T cell doses will be employed to reduce the risks of severe GVHD. For unrelated donor transplants, Bone Marrow will be used a the stem cell source if PBSC is not available.