Reduced Intensity Allogeneic Stem Cell Transplantation With Matched Unrelated Donors for Patients With Hematologic Malignancies

OBJECTIVES:

• To evaluate the safety and toxicity of a reduced-intensity conditioning regimen followed by allogeneic bone marrow or peripheral blood stem cell transplantation from an HLA-matched unrelated donor in patients with high-risk hematologic malignancies.
• To evaluate engraftment by peripheral blood chimerism analysis.
• To determine the incidence and severity of acute and chronic graft-versus-host disease following the transplant.
• To examine the possibility of controlling hematologic malignancies by induction of a graft-versus-leukemia/tumor effect.
• To determine the disease-free survival, relapse, transplant-related mortality, and death from all causes.

OUTLINE:

• Reduced-intensity conditioning regimen: Patients receive 1 of 2 conditioning regimens according to diagnosis.

• Regimen 1 (acute leukemia, myelodysplastic syndromes, myeloproliferative syndrome, or chronic myelogenous leukemia): Patients receive fludarabine phosphate IV over 30 minutes and busulfan IV over 3 hours on days -6 to -3 or orally 4 times daily on days -7 to -3.

• Regimen 2 (lymphoproliferative malignancies): Patients receive fludarabine phosphate IV over 30 minutes and cyclophosphamide IV over 1 hour on days -5 to -3. Patients with CD20+ malignancies also receive rituximab IV over 4-6 hours on days -13, -6, 1, and 8.

• Transplantation: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0.

• Graft-versus-host disease (GVHD) prophylaxis: Patients receive low-dose alemtuzumab subcutaneously on days -11 to -9 and tacrolimus IV over 24 hours beginning on day -3 and then orally twice daily beginning on day 14 and continuing until day 60, followed by a taper until day 180 in the absence of clinically significant GVHD. Patients also receive methotrexate on days 1, 3, and 6.