• Post-transplant immunosuppression regimen with ≤ 20% incidence of a grade II-IV graft-versus-host-disease (GVHD) and < 10% incidence of nonengraftment (< 5% donor chimerism) at day 60 following transplant
  
• Incidence and severity of acute GVHD at day 60 following transplant
  
• Frequency of mixed chimerism defined as any detectable donor cells at day 60 following transplant
  

OBJECTIVES:

• Determine a minimal (short-duration) post-transplant immunosuppression regimen comprising cyclophosphamide and/or mycophenolate mofetil with or without tacrolimus that results in ≤ 20% incidence of grade II or higher acute graft-versus-host disease (GVHD) in patients with hematologic malignancies undergoing nonmyeloablative allogeneic bone marrow or peripheral blood stem cell transplantation from an HLA-identical related donor.
• Determine the post-transplant immunosuppression regimen that results in < 10% incidence of nonengraftment, defined as < 5% donor chimerism in peripheral blood at day 60, in these patients.
• Determine the incidence and severity of acute GVHD in patients treated with these regimens.
• Determine the frequency of mixed chimerism in patients treated with these regimens.

OUTLINE:

• Nonmyeloablative allogeneic bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT): Patients receive fludarabine IV on days -4 to -2 and undergo total-body irradiation on day -1. Patients undergo allogeneic BMT on day 0 or PBSCT on day 0 (and days 1 and 2, if needed). Patients receive filgrastim (G-CSF) beginning on day 5 and continuing until at least day 15 or until blood counts recover.

• Sequentially increasing levels of post-transplant immunosuppression: Cohorts of patients are enrolled into 1 of the following regimens:

  • Regimen 1 (post-BMT immunosuppression): Patients receive cyclophosphamide IV on day 3 only.
  • Regimen 2 (post-BMT immunosuppression): Patients receive mycophenolate mofetil (MMF) once on day 3 and then twice daily on days 4-32.
  • Regimen 3 (post-BMT immunosuppression): Patients receive cyclophosphamide IV on days 3 and 4 and MMF twice daily on days 4-33.
  • Regimen 4 (post-PBSCT immunosuppression): Patients receive cyclophosphamide and MMF as in regimen 3.
  • Regimen 5 (post-PBSCT immunosuppression): Patients receive cyclophosphamide and MMF as in regimen 3 and tacrolimus twice daily on days 4-33.

Cohorts of approximately 10-20 patients receive sequentially increasing levels of post-transplant immunosuppression until a minimal (short-duration) post-transplant immunosuppression regimen is identified. The minimal post-transplant immunosuppression regimen is defined as the regimen in which ≤ 3 of 10 or ≤ 6 of 20 patients develop grade II or higher acute graft-versus-host disease AND ≤ 2 of 10 or ≤ 4 of 20 patients fail to engraft 60 days post-transplantation. Once the minimal post-transplant immunosuppression regimen is identified, an additional 10 patients are treated with that regimen.

Patients are followed for 60 days after transplantation.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following hematologic malignancies:

  • Stage II or III multiple myeloma
  • Amyloidosis

  • Myelofibrosis with ≥ 2 of the following high-risk features:

    • Over 55 years of age
    • Hemoglobin < 10 g/dL
    • WBC < 3,000/mm^3 OR > 10,000/mm^3
    • Platelet count < 100,000/mm^3
    • Cytogenetic abnormalities

  • Mycosis fungoides, meeting 1 of the following criteria:

    • Stage IIB or III disease with evidence of histologic conversion to an aggressive lymphoma

      • Must demonstrate chemosensitivity
    • Stage IV disease

  • Paroxysmal nocturnal hemoglobinuria

    • Not meeting criteria for other bone marrow transplantation (BMT) or treatment studies

  • Diagnosis of 1 of the following hematologic malignancies, for which patient is not eligible for potentially curative allogeneic BMT due to end-organ dysfunction, age 65 to 75, or the amount of prior chemotherapy:

    • Acute myeloid or acute lymphoblastic leukemia

      • High-risk disease in first or second (or further) complete remission

    • Relapsed aggressive non-Hodgkin's lymphoma

      • Not eligible for autologous or standard allogeneic BMT

    • Hodgkin's lymphoma in second or further complete or partial remission

      • Not eligible for autologous or standard allogeneic BMT

    • Myelodysplastic syndromes or myelodysplastic/myeloproliferative diseases

      • Any of the following subtypes:

        • Refractory anemia with excess blasts (RAEB)
        • RAEB in transformation
        • Chronic myelomonocytic leukemia
        • Any morphologic subtype with multiple chromosomal abnormalities
        • Any subset with life-threatening cytopenias in all 3 cell lines, defined as platelet count ≤ 20,000/mm^3, absolute neutrophil count ≤ 500/mm^3, and reticulocyte count ≤ 50,000/mm^3

      • Meets both of the following criteria:

        • Less than 20% blasts by bone marrow biopsy
        • Not eligible for standard allogeneic BMT
      • No refractory anemia with ringed sideroblasts
      • No 5q syndrome

    • Stage III or IV chronic lymphocytic leukemia

      • Not meeting criteria for other BMT studies

    • Chronic myelogenous leukemia in first or second chronic phase

      • Not meeting criteria for other BMT studies or treatment

    • Stage III or IV indolent small lymphocytic or follicular lymphoma

      • Not eligible for autologous or standard allogeneic BMT or other active protocols at Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Must have an HLA-identical related donor available

PATIENT CHARACTERISTICS:

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• Bilirubin ≤ 3.0 mg/dL
• AST ≤ 175 U/L
• ALT ≤ 200 U/L

Renal

• Creatinine ≤ 3.0 mg/dL

Cardiovascular

• LVEF ≥ 30%

Pulmonary

• FEV_1 ≥ 40% predicted
• Forced vital capacity ≥ 40% predicted

Other

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

PRIOR CONCURRENT THERAPY:

Chemotherapy

• See Disease Characteristics