Cyclophosphamide and Total Body Irradiation in Treating Patients Who Are Undergoing an Autologous Peripheral Stem Cell Transplant For Chronic Lymphocytic Leukemia

OBJECTIVES:

Primary

• Determine the safety and feasibility of autologous peripheral blood stem cell transplantation in patients with chronic lymphocytic leukemia treated with cyclophosphamide and total-body irradiation.

Secondary

• Determine the safety, feasibility, and efficacy of combination therapy comprising dexamethasone, carmustine, cytarabine, etoposide, and melphalan (Dexa-BEAM) and filgrastim (G-CSF) mobilization in patients treated with this regimen.
• Determine the efficacy of ex-vivo graft purging in patients treated with this regimen.
• Determine the incidence of complete clinical and molecular remissions in patients treated with this regimen.
• Determine the progression-free survival of patients treated with this regimen.

OUTLINE: This is a multicenter, open-label, nonrandomized study.

• Cytoreductive treatment: Patients undergo 2-4 courses of cytoreductive treatment, preferably following the fludarabine and cyclophosphamide (FC) protocol.
• Stem cell mobilization: Patients achieving a complete remission (CR) or partial remission (PR) and stable blood counts undergo stem cell mobilization comprising dexamethasone, carmustine, cytarabine, etoposide, melphalan (Dexa-BEAM), and filgrastim (G-CSF). Patients with an adequate number of mobilized cells undergo stem cell collection. Patients with CR or very good PR proceed to myeloablative therapy.
• Myeloablative therapy: Patients undergo total-body irradiation on day -4 and receive cyclophosphamide IV on days -4 and -3.
• Autologous peripheral blood stem cell transplantation (PBSCT): Patients undergo autologous PBSCT on day 0.

After completion of study, patients are followed periodically.

PROJECTED ACCRUAL: A total of 150 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Patients with chronic lymphocytic leukemia, meeting 1 of the following criteria:

• Binet stage B or C disease
• Binet stage A disease and at high risk for disease progression, defined as the following:

• Non-nodular marrow infiltration or lymphocyte doubling time < 12 months
• Thymidine kinase > 7.0 U/L or ß-2-microglobulin > 3.5 mg/L
• Polymerase chain reaction-amplifiable clonal CDRIII rearrangement of the IgV_H

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• No concurrent disease resulting in major organ dysfunction

PRIOR CONCURRENT THERAPY:

• No prior combination therapy comprising melphalan, dexamethasone, carmustine, cytarabine, and etoposide (DEXA-Beam)
• No more than 1 prior chemotherapy regimen
• No prior chemotherapy regimen longer than 6 months in duration