RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing
so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer
cells. Combining chemotherapy and radiation therapy with peripheral stem cell
transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill
more cancer cells.
PURPOSE: Phase I trial to study the effectiveness of high-dose combination chemotherapy
followed by total-body irradiation and peripheral stem cell transplantation in treating
patients with chronic lymphocytic leukemia.
OBJECTIVES: I. Evaluate engraftment after autografting with CD34 selected peripheral blood
stem cells (PBSC) in patients with chronic lymphocytic leukemia (CLL). II. Evaluate the
efficacy of CD34 selection for purging CLL from PBSC collection. III. Determine the
effectiveness of mobilization chemotherapy with cyclophosphamide, etoposide, and
dexamethasone plus filgrastim (granulocyte colony-stimulating factor) to mobilize PBSC in
these patients. IV. Describe toxicity and disease response to a conditioning regimen of
total body irradiation and cyclophosphamide in these patients.
OUTLINE: There are 3 phases to the treatment plan: Cytoreductive chemotherapy can be given
by conventional chemotherapy. Patients are treated until at least a good partial remission.
Patients will have CD34 selected peripheral blood stem cells (PBSC) stored after treatment
with mobilization chemotherapy followed by filgrastim (granulocyte colony-stimulating
factor; G-CSF). Cyclosphosphamide (CTX) IV is given over 1 hour. Etoposide (VP-16) is given
over 1-2 hours on day 2. Dexamethasone is given 4 times a day on days 1-3. G-CSF is given
subcutaneously daily beginning 2 days after chemotherapy and continuing until PBSC
collection is completed. At least 4 weeks should ensue after mobilization chemotherapy
before proceeding with the transplant. Patients are treated with TBI on days -6, -5, and -4
and CTX on days -3 and -2. PBSC are infused on day 0.
PROJECTED ACCRUAL: A total of 15 patients will be entered in this study.
DISEASE CHARACTERISTICS: Diagnostically proven intermediate, advanced, or high risk
chronic lymphocytic leukemia of the B cells with marrow tumor reduced by prior therapy
Marrow tumor content no greater than 30% of total nucleated cells Patients age 50 and
under who have high risk disease are eligible Patients age 65 and under who have
intermediate or high risk disease that has failed at least 1 therapy including an
alkylating agent or fludarabine are eligible No history of transformation to aggressive
lymphoma (Richter's syndrome)
PATIENT CHARACTERISTICS: Age: 17 to 65 Performance status: Karnofsky 70%-100% Life
expectancy: Not severely limited by illness other than leukemia Hematopoietic: Absolute
neutrophil count greater than 2,000/mm3 (no growth factor support) Platelet count greater
than 120,000/mm3 (unless documented active autoimmune thrombocytopenia) Hemoglobin greater
than 10 g/dL (unless documented active autoimmune anemia) No coexisting myelodysplasia
Hepatic: Bilirubin no greater than 2.0 mg/dL Renal: Creatinine clearance at least 50
mL/min Cardiovascular: No cardiac disease that would limit ability to receive
cytoreductive therapy and compromise survival Pulmonary: No pulmonary disease that would
limit ability to receive cytoreductive therapy and compromise survival Other: No HIV
antibody Not pregnant
PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior radiation therapy to chest
or abdomen greater than 2,000 Gy