OBJECTIVES:

• Determine the minimum effective dose of pretransplant cyclophosphamide to induce engraftment of haploidentical allogeneic bone marrow without the use of myeloablative conditioning in patients with hematologic malignancies.
• Determine the incidence and severity of graft versus host disease and nonhematologic toxicities with this treatment regimen in these patients.
• Correlate the pretreatment phenotypic and functional immunologic characteristics in these patients in relation to risk of graft rejection with this treatment regimen.

OUTLINE: This is a dose-escalation study of cyclophosphamide.

Patients receive fludarabine IV over 1 hour on days -6 to -2; cyclophosphamide IV over 1 hour on days -6, -5, and 3; total body irradiation on day -1; and allogeneic bone marrow transplantation on day 0. Patients also receive tacrolimus IV or orally twice a day on days 4-50; oral mycophenolate mofetil on days 4-35; and filgrastim (G-CSF) subcutaneously or IV starting on day 4 and continuing until blood counts recover.

Cohorts of 3-6 patients receive escalating doses of cyclophosphamide until the minimum effective dose necessary to induce chimerism without unacceptable toxicity in these patients is determined.

Patients are followed at 2 and 6 months, at one year, and then annually thereafter.

PROJECTED ACCRUAL: At least 23 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Patients with any of the following diagnoses:

  • Chronic myelogenous leukemia

    • Chronic phase 1

      • Failed prior interferon alfa therapy OR
      • Relapsed after prior autologous stem cell transplantation
    • Chronic phase 2

  • Acute leukemia

    • Standard risk

      • Age over 60 years
      • Complete remission 1 (CR1)

    • High risk

      • High WBC at presentation, unfavorable cytogenetics, mixed lineage, delayed response to induction chemotherapy
      • CR1
      • Complete remission 2 or higher

  • Acute lymphocytic leukemia

    • CR1 or higher

  • Myelodysplastic syndrome

    • Untreated OR
    • CR1
  • Acute myeloid leukemia in CR1

  • Chronic lymphocytic leukemia

    • Rai stage III or IV OR
    • Received prior autologous stem cell transplantation

  • Multiple myeloma

    • Stage II or III
    • Stable or progressive disease after prior chemotherapy OR
    • Received prior autologous stem cell transplantation
  • Non-Hodgkin's Lymphoma
  • Hodgkin's lymphoma
• Ineligible for or refused autologous or standard allogeneic bone marrow transplantation
• Ineligible for bone marrow transplantation from an HLA matched, sibling donor or from an HLA matched, unrelated donor
• Must have an HLA mismatched, related donor (3-5 out of 6)

PATIENT CHARACTERISTICS:

Age:

• 0.5 to 70

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin less than 3.1 mg/dL

Renal:

• Not specified

Cardiovascular:

• Left ventricular ejection fraction at least 35%

Pulmonary:

• FEV_1 and FVC at least 40% of predicted OR
• FEV_1 and FVC at least 60% in patients who have received prior thoracic or mantle radiotherapy

Other:

• HIV negative
• No other debilitating medical or psychiatric illness that would preclude study compliance
• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics
• No prior transfusions from donor

Chemotherapy:

• See Disease Characteristics

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified