Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation For Patients With Disease Relapse Or Myelodysplasia After Prior Autologous Transplantation

Brief Summary

Detailed Description

OBJECTIVES: * Determine the feasibility of non-myeloablative allogeneic hematopoietic stem cell transplantation by demonstrating that the risk of treatment-related mortality during the first 6 months is an acceptable rate of less than 40% in patients with relapsed hematologic malignancies after prior high-dose chemotherapy and autologous stem cell transplantation. * Determine the response rates (disease-specific partial and complete response) in patients treated with this regimen. * Determine the 6-month and 12-month probabilities of response in patients treated with this regimen. * Determine the distribution of time-to-progression in patients responding to this regimen. * Determine the percent donor chimerism in patients treated with this regimen. * Determine the risk of acute and chronic graft-vs-host disease in patients treated with this regimen. * Determine the toxic effects of this regimen in these patients. * Determine the disease-free and overall survival of patients treated with this regimen. OUTLINE: This is an open-label study. * Preparative Regimen: Patients receive fludarabine IV over 30 minutes on days -7 to -3 and busulfan IV over 2 hours every 6 hours (for a total of 8 doses) on days -4 and -3. * Graft vs Host Disease (GVHD) Prophylaxis: Patients who have an HLA-identical donor receive oral (or IV if unable to tolerate oral administration) tacrolimus twice daily on days -1 to 90 followed by a taper\^\* until day 150 and methotrexate IV on days 1, 3, and 6. Patients with a matched related or matched unrelated donor receive oral (or IV if unable to tolerate oral administration) tacrolimus twice daily on days -1 to 180 followed by a taper\^\* as tolerated; methotrexate IV on days 1, 3, 6, and 11; oral mycophenolate mofetil twice daily on days -2 to 60 followed by a taper; and rabbit anti-thymocyte globulin IV over 4-6 hours on days -4 to -1 (for a total of 4 doses). NOTE: \*Tacrolimus may be tapered on days 60-90 if donor chimerism of CD3+ cells is less than 50% at day 60 or patient has progressive disease * Allogeneic Stem Cell Transplantation: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on days 0 and 1. Patients then receive filgrastim (G-CSF) subcutaneously daily beginning on day 7 and continuing until blood counts recover. * Donor Lymphocyte Infusion (DLI): After day 180 (or day 210 for patients without an HLA-identical donor), patients with stable or progressive disease and no active GVHD may receive up to 3 DLIs every 8 weeks. Patients are followed within 2-3 months, every 3 months for 2 years, and then every 6 months for 3 years.

Primary Outcomes

Secondary Outcomes

• Per cent donor chimerism(30, 60, 90, 180 days post transplant)
• Disease-free survival(12 months up to 5 years post study entry)
• Graft-versus-host disease incidence(6 months post transplant)
• Response Rates(6 and 12 months)