OBJECTIVES:

• Determine the efficacy of non-myeloablative allogeneic hematopoietic stem cell transplantation from related and unrelated donors in patients with myelodysplastic syndromes or myeloproliferative disorders.
• Determine the safety profile of this regimen, in terms of incidence of graft-vs-host disease, graft rejection, and non-relapse mortality, in these patients.
• Determine the efficacy of a strategy for donor lymphocyte infusion based primarily on defined criteria of persistent or progressive disease in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to donor status (related vs unrelated).

• Conditioning:Patients receive fludarabine IV over 30 minutes once daily on days -4 to -2. Patients undergo total body irradiation on day 0.

• Immunosuppression:

  • Related Donor:Patients receive oral cyclosporine twice daily beginning on day -3 followed by a taper beginning on day 56 and continuing until day 81 or day 177 in the absence of graft-vs-host disease (GVHD). Patients also receive oral mycophenolate mofetil twice daily on days 0-27.
  • Unrelated Donor:Patients receive oral cyclosporine twice daily beginning on day -3 followed by a taper beginning on day 100 and continuing until day 180 in the absence of GVHD. Patients also receive mycophenolate mofetil three times daily beginning on day 0 followed by a taper beginning on day 40 and continuing until day 96.
• Allogeneic Hematopoietic Stem Cell Transplantation (AHSCT): Patients undergo AHSCT transplantation on day 0.
• Donor lymphocyte infusion (DLI): Eligible patients (at least mixed hematopoietic chimerism, no GVHD, and persistent or progressive disease) may receive DLI IV over 30 minutes beginning 1-2 weeks after immunosuppression. Patients may receive up to 3 infusions.

Patients are followed at months 3, 4, 6, 9, 12, 18, and 24 and then annually thereafter.

PROJECTED ACCRUAL: A total of 200 patients (100 per stratum) will be accrued for this study within 3 years.

DISEASE CHARACTERISTICS:

• Myelodysplastic syndromes (MDS)

  • Diagnosis of MDS classifiable by the FAB system as any of the following:

    • Refractory anemia (RA)
    • RA with ringed sideroblasts
    • RA with excess blasts (RAEB)
    • RAEB in transformation
    • Chronic myelomonocytic leukemia
    • MDS transformed to acute leukemia
  • Patients with advanced MDS must be cytoreduced to less than 10% marrow blasts within past 21 days

  • High-risk disease by the International Prognostic Scoring System (IPSS) score (e.g., "intermediate-2" or "high risk")

    • Lower-risk disease by the IPSS score (e.g., "intermediate-1" or "low risk") allowed if evidence of progression is present (e.g., an increasing transfusion requirement)

• Myeloproliferative disorders

  • Diagnosis of any of the following:

    • Atypical chronic myelogenous leukemia and Philadelphia chromosome-negative

      • Chronic phase
      • Excess blasts or blastic transformation
    • Polycythemia vera with persistent thrombotic or hemorrhagic complications despite conventional therapy OR progressed to post-polycythemic marrow fibrosis
    • Essential thrombocythemia with persistent thrombotic or hemorrhagic complications despite conventional therapy OR progressed to myelofibrosis

    • Agnogenic myeloid metaplasia with 1 of the following criteria:

      • High-risk disease according to the Lille scoring system (e.g., "intermediate" or "high risk")
      • Lower-risk disease according to the Lille scoring system (e.g., "low risk") with abnormal cytogenetics
• Ineligible for a curative autologous transplantation
• No active CNS involvement

• Related donor

  • Genotypically or phenotypically HLA-identical
  • ABO incompatibility acceptable
  • No identical twin OR

• Unrelated donor

  • HLA-matched for HLA-DRB1 and DQB1
  • Serologic match for all recognized HLA-A, HLA-B, and HLA-C antigens
  • Molecular match for at least 5 of 6 HLA-A, HLA-B, or HLA-C antigens
  • ABO incompatibility acceptable
  • No bone marrow donors

PATIENT CHARACTERISTICS:

Age

• 50 to 74 OR

• Under 50 and at high risk for regimen-related toxicity using standard high-dose regimens

  • High-risk factors include pre-existing conditions such as chronic lung, kidney, liver, or heart disease

Performance status

• Karnofsky 70-100%

Life expectancy

• Not specified

Hematopoietic

• See DIsease Characteristics

Hepatic

• See Age
• Bilirubin no greater than 2 times upper limit of normal (ULN)
• AST or ALT no greater than 4 times ULN

Renal

• See Age

Cardiovascular

• See Age
• Ejection fraction at least 40%
• No symptomatic congestive heart failure requiring therapy
• No poorly controlled cardiac arrhythmias
• No poorly controlled hypertension with inability to maintain a steady blood pressure of 150/90

Pulmonary

• See Age
• No requirement for supplemental oxygen
• DLCO at least 50% of predicted
• Total lung capacity at least 30%
• FEV_1 at least 30%

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 1 year after study completion
• HIV negative
• No severe psychological illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent hematopoietic growth factors during mycophenolate mofetil administration

Chemotherapy

• At least 21 days since prior chemotherapy and recovered

  • Hydroxyurea or anagrilide to manage elevated cell counts allowed up until beginning of study therapy

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified