High-Dose Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Hematologic Cancer

OBJECTIVES:

• Determine the safety and feasibility of using allogeneic peripheral blood progenitor cell infusions obtained from normal histocompatible sibling donors for reconstituting bone marrow and immunologic function when given after high-dose busulfan/cyclophosphamide in patients with a hematologic malignancy.
• Determine the efficacy of this treatment in these patients.
• Determine the ability to mobilize hematopoietic progenitor cells from normal donors given filgrastim (G-CSF) by determining the hematopoietic progenitor cell content of allogeneic peripheral blood progenitor cell collections.
• Determine the incidence of engraftment failures in these patients.
• Determine the incidence of severe acute graft-versus-host disease in these patients.

OUTLINE: Patients receive high-dose oral busulfan every 6 hours on days -8 to -5, cyclophosphamide IV twice a day on days -4 and -3, and cyclosporine IV over 6 hours on day -1 and then 10 hours on day 0 for 2 doses (allogeneic only). Allogeneic peripheral blood progenitor cells IV are administered on day 0.

Filgrastim (G-CSF) is administered subcutaneously twice a day beginning 3 hours after completion of cell infusion and continuing until blood counts recover.

Patients are followed every month for 2 months, every 3 months for 6 months, and then every 6 months until disease progression.

PROJECTED ACCRUAL: A total of 40 patients will be accrued over a 15 month period.

DISEASE CHARACTERISTICS:

• Histologically diagnosed:

• Acute myeloid leukemia in first, second, or third complete remission or first or second early relapse
• Acute lymphoblastic leukemia in first, second, or third complete remission or first or second early relapse
• Hodgkin's lymphoma in second or third remission or first, second, or third relapse, or refractory
• Non-Hodgkin's lymphoma in second or third remission or first, second, or third relapse, or refractory
• Multiple myeloma and plasma cell leukemia in second or third remission or first, second, or third relapse, or refractory
• Myelodysplastic syndrome deemed suitable for allogeneic bone marrow transplantation
• No symptoms or signs of CNS involvement and CNS is disease free on lumbar puncture and brain CT scan
• No active meningeal cancer

PATIENT CHARACTERISTICS:

Age:

• 4 to 55 (4 to 60 if donor is identical twin)

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• SGOT/SGPT less than 3 times normal
• Bilirubin less than 2.0 mg/dL

Renal:

• Creatinine less than 2.1 mg/dL
• Creatinine clearance at least 60 mL/min (no greater than 1.5 times normal for children under 40 kg)

Cardiovascular:

• No uncontrolled hypertension
• No uncontrolled congestive heart failure
• No active angina pectoris requiring nitrates
• At least 6 months since prior myocardial infarction
• No major ventricular arrhythmia
• Left ventricular ejection fraction at least 45% on MUGA

Pulmonary:

• No severe or symptomatic restrictive or obstructive lung disease
• FEV_1 greater than 50% of predicted
• DLCO greater than 50% of predicted

Neurologic:

• No severe central or peripheral neurologic abnormality

Other:

• Must have HLA-A,B,C,D/DR identical sibling age 4 to 65, in good health
• No insulin-dependent diabetes mellitus
• No major thyroid or major adrenal dysfunction
• No active infection
• No other active malignancy
• Not pregnant
• HIV negative
• HTLV-I and HTLV-II negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No excessive anthracycline exposure, unless endomyocardial biopsy shows less than grade 2 drug effect and cardiac scan shows at least 50% ejection fraction
• At least 1 year since prior autologous bone marrow or peripheral blood progenitor cell transplant or allogeneic bone marrow transplant

Chemotherapy:

• At least 3 weeks since prior chemotherapy
• No prior excessive carmustine and bleomycin

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 3 weeks since prior radiotherapy

Surgery:

• Not specified

Other:

• No concurrent nitroglycerin for angina pectoris
• No concurrent anti-arrhythmic drugs for major ventricular dysrhythmias