RATIONALE: Combining antithymocyte globulin with combination chemotherapy before donor peripheral stem cell transplantation may reduce the chance of developing graft-versus-host disease following transplantation.

PURPOSE: Phase I/II trial to study the effectiveness of combining antithymocyte globulin with busulfan and cyclophosphamide in reducing graft-versus-host disease in patients who are undergoing donor stem cell transplantation for myelodysplastic syndrome or other myeloproliferative disorder.

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.

• Chronic Myeloproliferative Disorders
• Graft Versus Host Disease
• Leukemia
• Myelodysplastic Syndromes
• Myelodysplastic/Myeloproliferative Diseases

• Biological: anti-thymocyte globulin
• Drug: busulfan
• Drug: cyclophosphamide
• Drug: cyclosporine
• Drug: methotrexate
• Procedure: allogeneic bone marrow transplantation
• Procedure: peripheral blood stem cell transplantation

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following:

  • Myelodysplastic syndromes (including those that have evolved to acute myeloid leukemia)

  • Myeloproliferative disorders

    • No chronic myelogenous leukemia
  • Other diseases eligible for conditioning with targeted busulfan, cyclophosphamide, and anti-thymocyte globulin that are not candidates for other studies

• Available related or unrelated donor compatible for HLA-A, -B, -C, DRB1, and DQB1

  • A single allele mismatch at HLA-A, -B, -C, or DRB1 is allowed

PATIENT CHARACTERISTICS:

Age

• 65 and under

Performance status

• Not specified

Life expectancy

• No severe limitation due to other diseases

Hematopoietic

• Not specified

Hepatic

• AST no greater than 2 times normal
• No hepatic disease

Renal

• Creatinine no greater than 2 times upper limit of normal OR
• Creatinine clearance at least 50% for age, gender, and weight

Cardiovascular

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

Pulmonary

• No severe or mild hypoxemia

  • pO_2 at least 70 mm Hg and DLCO at least 70% of predicted OR
  • pO_2 at least 80 mm Hg and DLCO at least 60% of predicted

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No growth factors given posttransplantation concurrently with methotrexate immunosuppression

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified