Trial Information

Conditioning With Targeted Busulfan, Cyclophosphamide and Thymoglobulin for Allogeneic Marrow or Peripheral Blood Stem Cell (PBSC) Transplantation for Myelodysplasia and Myeloproliferative Disorders

OBJECTIVES:

- Determine the incidence of acute graft-vs-host disease (GVHD) requiring therapy in
patients with myelodysplastic syndromes or myeloproliferative disorders treated with
busulfan, cyclophosphamide, and anti-thymocyte globulin prior to transplantation with
filgrastim (G-CSF)-mobilized peripheral blood stem cells (or bone marrow) from related
or unrelated donors.

- Determine the incidence of relapse and relapse-free survival in patients treated with
this regimen.

- Determine the incidence of non-relapse mortality by day 100 and 1 year
posttransplantation in patients treated with this regimen.

- Determine the incidence of Epstein-Barr virus reactivation, infections, and chronic
GVHD in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of anti-thymocyte globulin.

- Conditioning and graft-vs-host disease (GVHD) prophylaxis: Patients receive oral
busulfan every 6 hours on days -7 to -4 (16 doses), cyclophosphamide IV on days -3 and
-2, and anti-thymocyte globulin IV over 3 hours on days -3, -2, and -1.

Cohorts of 15 patients receive adjusted doses of anti-thymocyte globulin to determine the
optimal dose at which Epstein-Barr virus (EBV) activation and GVHD are reduced. The optimal
dose is the dose at which 2 consecutive cohorts receive the same regimen.

- Stem cell transplantation: Patients undergo peripheral blood stem cell (PBSC) or bone
marrow transplantation on day 0.

- Posttransplantation GVHD prophylaxis: Patients receive cyclosporine IV continuously on
days -1 to 4 and then orally twice daily until day 180. Patients also receive
methotrexate on days 1, 3, 6, and 11.

Patients are followed every 6 months for 2 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 30-45 patients will be accrued for this study within 2 years.