• Incidence of grade II, III, and IV graft-versus-host disease [ Designated as safety issue: No ]
  

OBJECTIVES:

• Determine the incidence of grades II, III, and IV graft-vs-host disease (GVHD) in patients with myelodysplastic syndromes (MDS), acute myeloid leukemia transformed from MDS, or myeloproliferative disorders treated with immunologically engineered, filgrastim (G-CSF)-mobilized, allogeneic peripheral blood stem cell transplantation.
• Determine the incidence of graft failure, relapse, and transplant-related mortality by day 100 in patients treated with this regimen.
• Determine the incidence of chronic GVHD, in terms of number and duration of immunosuppressant therapies, in patients treated with this regimen.
• Determine the feasibility of partial T-cell depletion in G-CSF-mobilized peripheral blood stem cells.

OUTLINE: Patients receive conditioning with oral busulfan every 6 hours on days -7 to -4 and cyclophosphamide IV on days -3 and -2. Immunologically engineered, filgrastim (G-CSF)-mobilized, allogeneic peripheral blood stem cells are infused on day 0.

Patients receive graft-vs-host disease prophylaxis comprising methotrexate IV on days 1, 3, 6, and 11 and cyclosporine IV over 1-4 hours (orally twice daily when tolerated) on days -1 to 80 and then gradually tapered over 5 months beginning on day 81.

Patients are followed regularly through day 100 and then at 1 year.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 3 years.

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following:

  • Myelodysplastic syndromes (MDS) that has advanced beyond refractory anemia (RA)
  • RA with excess blasts (RAEB) (greater than 5% blasts)
  • RAEB in transformation (greater than 20% but less than 30% blasts)
  • Acute myeloid leukemia (greater than 30% blasts) that evolved from MDS
  • Myeloproliferative disorder, including chronic myelomonocytic leukemia, agnogenic myeloid metaplasia, polycythemia vera, or essential thrombosis
• No chronic myelogenous leukemia with or without excess (greater than 5%) blasts
• Must have an HLA-identical, related donor

PATIENT CHARACTERISTICS:

Age

• 18 to 65

Performance status

• Not specified

Life expectancy

• At least 6 months

Hematopoietic

• Not specified

Hepatic

• Bilirubin less than 2 times upper limit of normal (ULN)*
• SGOT/SGPT less than 2 times ULN* NOTE: * Unless due to malignancy

Renal

• Creatinine no greater than 2.0 mg/dL OR
• Glomerular filtration rate at least 60 mL/min

Cardiovascular

• Cardiac ejection fraction at least 45%

Pulmonary

• DLCO at least 60% of predicted

Other

• HIV negative
• Human antimouse antibody negative
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other medical condition that would preclude study participation
• No hypersensitivity to cyclosporine

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior marrow transplantation
• No concurrent growth factors for 21 days after study transplantation

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified