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

Allogeneic Peripheral Blood Progenitor Cell Transplantation Using Histocompatible Sibling-Matched Donor Cells After High-Dose Busulfan/Cyclophosphamide as Therapy for Hematologic Malignancies

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving busulfan, cyclophosphamide, and filgrastim together with peripheral stem cell transplantation from a sibling donor works 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