RATIONALE: Giving chemotherapy, such as fludarabine phosphate, busulfan, and cyclophosphamide, and total-body radiation therapy before a donor peripheral stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. It is not yet known whether low-dose chemotherapy and total-body radiation therapy is more effective than high-dose chemotherapy in treating patients with myelodysplastic syndrome or acute myeloid leukemia. PURPOSE: This phase III trial is studying low-dose conditioning to see how well it works compared to high-dose conditioning followed by peripheral blood stem cell transplant in treating patients with myelodysplastic syndromes or acute myeloid leukemia
OBJECTIVES: I. Determine whether the conditioning intensity affects outcomes after HCT in patients with MDS or AML who have \< 5% marrow myeloblasts at the time of HCT. OUTLINE: Patients are randomized to 1 of 2 treatment arms. Arm I (Nonmyeloablative regimen): CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo low-dose total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) infusion on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine every 12 hours on days -3 to 57 with taper on days 57-177 or cyclosporine every 12 hours on days -3 to 100 with taper on days 101-177. Patients also receive oral mycophenolate mofetil every 12 hours on days 0-27 or every 8 hours on days 0-40 with taper on days 41-96. Arm II (Myeloablative regimen): CONDITIONING: Patients are assigned to 1 of 2 treatment groups. Group A: Patients receive fludarabine IV once daily and oral busulfan four times daily or busulfan IV over 3 hours on days -5 to -2. Group B: Patients receive cyclophosphamide IV over 1-2 hours on days -3 and -2 and oral busulfan four times daily or busulfan IV over 3 hours on days -7 to -4. TRANSPLANTATION: Patients undergo PBSC infusion on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally every 12 hours on days -1 to 56 and taper on days 57-200. Patients also receive methotrexate IV on days 1, 3, 6, and 11. Treatment in both arms continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
25
Radiation
Undergo allogeneic transplantation
Given IV
Given orally
Given IV or orally
Given IV or orally
Given IV
Undergo transplantation
Undergo allogeneic transplantation
Correlative studies
Correlative studies
Correlative studies
Correlative studies
Correlative studies
Correlative studies
Given IV or orally
Given IV
HealthOne Presbyterian St. Lukes Medical Center
Denver, Colorado, United States
Emory University
Altanta, Georgia, United States
Weill Cornell University
New York, New York, United States
University of Utah
Salt Lake City, Utah, United States
Veterans Administration Center-Seattle
Seattle, Washington, United States
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States
Medical College Wisconsin
Milwaukee, Wisconsin, United States
Technical University Dresden
Dresden, Saxony, Germany
Overall Survival
Time frame: At 2 years
Progression-free Survival
IWG criteria was used to determine disease progression
Time frame: After stem cell infusion to date of last follow up.
Non-relapse Mortality
Time frame: At 100 days
Donor Cell Engraftment
Chimerism analysis was performed in patients who recieved nonmyeloablative tranplsnat. In this group the definition of engraftment was a CD3 count greater than 50%. In the myeloablative group, engraftment was defined as an absolute neutrophil count greater than 50%.
Time frame: After stem cell infusion to day 28
Incidence of Disease Progression/Relapse
Disease progression/relapse was defined by IWG criteria
Time frame: After stem cell infusion to date of last follow up.
Incidence and Severity of Acute and Chronic Graft-vs-host Disease
Time frame: After transplantation
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