Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Myelodysplastic Syndrome

OBJECTIVES:

• Determine the non-relapse toxicity and mortality on day 100 and at 1 year after transplantation in patients with low or intermediate-risk myelodysplastic syndrome treated with busulfan, cyclophosphamide, and allogeneic peripheral blood stem cell transplantation.
• Determine the incidence of donor stem cell engraftment and relapse-free survival in these patients treated with this regimen.
• Determine the incidence and severity of acute and chronic graft-versus-host disease and invasive fungal infections in these patients treated with this regimen.
• Determine the incidence of relapse in these patients treated with this regimen.

OUTLINE: Peripheral blood stem cells (PBSC) or bone marrow are harvested from a related or unrelated compatible donor. PBSC are selected for CD34+ cells.

Patients receive oral busulfan every 6 hours on days -7 to -4 and cyclophosphamide IV on days -3 and -2. Allogeneic PBSC or bone marrow is infused on day 0.

As graft-versus-host disease prophylaxis, patients receive cyclosporine IV beginning on day -1 and continuing orally twice daily (if feasible) until day 51 followed by a taper. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

Patients are followed through day 100, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 3 years.

DISEASE CHARACTERISTICS:

• Diagnosis of low or intermediate-risk myelodysplastic syndrome

• Refractory anemia (RA)
• RA with ringed sideroblasts
• No advanced myelodysplastic syndrome (i.e., at least 5% blasts in the marrow, more than 1% blasts in the peripheral blood, or blasts in the cerebrospinal fluid)
• No poor-risk cytogenetics (i.e., abnormalities of chromosome 7 or complex abnormalities)
• HLA-A, B, C, DRB1, and DQB1 compatible related or unrelated donor available

• Mismatch for a single HLA-A, B, C, DRB1, or DQB1 allele allowed

PATIENT CHARACTERISTICS:

Age:

• 65 and under

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• AST no greater than 2 times normal

Renal:

• Creatinine no greater than 2 times upper limit of normal
• Creatinine clearance at least 50%

Cardiovascular:

• No cardiac insufficiency requiring treatment
• No symptomatic coronary artery disease

Pulmonary:

• No severe hypoxemia (pO2 less than 70 mm Hg with DLCO less than 70% predicted)
• No mild hypoxemia (pO2 less than 80 mm Hg with DLCO less than 60% predicted)

Other:

• No other disease that would limit life expectancy
• HIV negative
• Not pregnant or nursing

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified