• Treatment-related mortality [ Designated as safety issue: No ]
  

• Complete response [ Designated as safety issue: No ]
  
• Complete or mixed donor chimerism [ Designated as safety issue: No ]
  
• Disease-free survival [ Designated as safety issue: No ]
  
• Graft-versus-host disease [ Designated as safety issue: No ]
  

OBJECTIVES:

• Determine the feasibility of non-myeloablative allogeneic hematopoietic stem cell transplantation by demonstrating that the risk of treatment-related mortality during the first 6 months is an acceptable rate of less than 40% in patients with relapsed hematologic malignancies after prior high-dose chemotherapy and autologous stem cell transplantation.
• Determine the response rates (disease-specific partial and complete response) in patients treated with this regimen.
• Determine the 6-month and 12-month probabilities of response in patients treated with this regimen.
• Determine the distribution of time-to-progression in patients responding to this regimen.
• Determine the percent donor chimerism in patients treated with this regimen.
• Determine the risk of acute and chronic graft-vs-host disease in patients treated with this regimen.
• Determine the toxic effects of this regimen in these patients.
• Determine the disease-free and overall survival of patients treated with this regimen.

OUTLINE: This is an open-label study.

• Preparative Regimen: Patients receive fludarabine IV over 30 minutes on days -7 to -3 and busulfan IV over 2 hours every 6 hours (for a total of 8 doses) on days -4 and -3.
• Graft vs Host Disease (GVHD) Prophylaxis: Patients who have an HLA-identical donor receive oral (or IV if unable to tolerate oral administration) tacrolimus twice daily on days -1 to 90 followed by a taper^* until day 150 and methotrexate IV on days 1, 3, and 6. Patients with a matched related or matched unrelated donor receive oral (or IV if unable to tolerate oral administration) tacrolimus twice daily on days -1 to 180 followed by a taper^* as tolerated; methotrexate IV on days 1, 3, 6, and 11; oral mycophenolate mofetil twice daily on days -2 to 60 followed by a taper; and rabbit anti-thymocyte globulin IV over 4-6 hours on days -4 to -1 (for a total of 4 doses).

NOTE: *Tacrolimus may be tapered on days 60-90 if donor chimerism of CD3+ cells is less than 50% at day 60 or patient has progressive disease

• Allogeneic Stem Cell Transplantation: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on days 0 and 1. Patients then receive filgrastim (G-CSF) subcutaneously daily beginning on day 7 and continuing until blood counts recover.
• Donor Lymphocyte Infusion (DLI): After day 180 (or day 210 for patients without an HLA-identical donor), patients with stable or progressive disease and no active GVHD may receive up to 3 DLIs every 8 weeks.

Patients are followed within 2-3 months, every 3 months for 2 years, and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 20-80 patients will be accrued for this study within 10-40 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed hematologic malignancy, including one of the following:

  • Chronic lymphocytic leukemia (CLL)

    • Absolute lymphocytosis greater than 5,000/mm^3
    • Lymphocytes must appear morphologically mature with less than 55% prolymphocytes
    • Lymphocyte phenotype with expression of CD19 and CD5

  • Prolymphocytic leukemia (PLL)

    • Morphologically confirmed
    • Absolute lymphocytosis greater than 5,000/mm^3
    • More than 55% prolymphocytes

  • Non-Hodgkin's lymphoma or Hodgkin's lymphoma

    • Any WHO histologic subtype allowed except mantle cell lymphoma
    • Core biopsies allowed if they contain adequate tissue for primary diagnosis and immunophenotyping
    • No bone marrow biopsy as the sole diagnostic means for follicular lymphoma

  • Multiple myeloma

    • Active disease requiring treatment
    • Durie-Salmon stage I, II, or III

  • Acute myeloid leukemia

    • Documented control (i.e., less than 10% bone marrow blasts and no circulating blasts)

  • Myelodysplastic syndromes

    • Documented disease by WHO criteria
• Must have evidence of relapse/progression at least 6 months after prior high-dose chemotherapy with autologous hematopoietic stem cell support
• Absence of CD23 expression for CLL or PLL allowed provided there is no morphologic evidence of mantle cell lymphoma

• Availability of any of the following donor types:

  • HLA-identical sibling (6/6)

  • 9/10 matched related donor by high-resolution molecular typing at HLA A, B, C, DRB1, and DQB1 loci

    • Only a single mismatch at one class I or II allele allowed
  • 10/10 matched unrelated donor by high-resolution molecular typing at HLA A, B, C, DRB1, and DQB1 loci
• No syngeneic donors

PATIENT CHARACTERISTICS:

Age

• Under 70

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• Bilirubin no greater than 3 times upper limit of normal (ULN)
• AST no greater than 3 times ULN

Renal

• Creatinine clearance at least 40 mL/min

Cardiovascular

• LVEF at least 30% by MUGA

Pulmonary

• DLCO greater than 40%
• No symptomatic pulmonary disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No uncontrolled diabetes mellitus
• No active serious infection
• No known hypersensitivity to E. coli-derived products

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• See Disease Characteristics
• More than 4 weeks since prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• More than 4 weeks since prior radiotherapy

Surgery

• More than 4 weeks since prior surgery