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, radiation therapy, and peripheral stem cell transplantation
may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.
PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy, radiation
therapy, and peripheral stem cell transplantation in treating patients who have stage III or
stage IV mantle cell lymphoma.
OBJECTIVES: I. Evaluate the response to a 8 week induction chemotherapy program consisting
of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in patients with mantle
cell lymphoma. II. Evaluate the efficacy of ifosfamide, carboplatin, and etoposide (ICE)
chemotherapy and filgrastim (G-CSF) for peripheral blood stem cell (PBSC) mobilization in
this patient population. III. Evaluate the safety and efficacy of ICE followed by total body
irradiation and high dose cyclophosphamide and etoposide in this patient population. IV.
Assess the contamination of PBSCs by lymphoma cells following mobilization by chemotherapy
and G-CSF in this patient population.
OUTLINE: Patients receive induction chemotherapy with cyclophosphamide IV, doxorubicin IV,
and vincristine IV on day 1, oral prednisone daily on days 2-6, and filgrastim (G-CSF)
subcutaneously daily on days 6-10. Treatment is repeated every 14 days for up to 4 courses.
Patients receive consolidation chemotherapy with ifosfamide IV over 24 hours and carboplatin
IV on day 2, etoposide IV daily on days 1-3, and G-CSF subcutaneously on days 5-12 for
course 1, and on day 5 for course 2 and continuing through peripheral blood stem cell (PBSC)
collection. Treatment is repeated every 14 days for 2 courses. Following PBSC collection,
patients receive total body irradiation twice a day for 4 days plus etoposide IV over 72
hours on days -6, -5, and -4 and cyclophosphamide IV daily on days -3 and -2. PBSCs are
infused on day 0. Patients receive G-CSF IV or subcutaneously twice a day beginning on day
1. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and
PROJECTED ACCRUAL: Approximately 14-24 patients will be accrued for this study within two
DISEASE CHARACTERISTICS: Histologically confirmed stage III or IV mantle cell lymphoma
(diffuse, nodular, mantle zone, or blastic variants)
PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Not specified Life
expectancy: Not specified Hematopoietic: Not specified Hepatic: No chronic active or
persistent hepatitis Bilirubin less than 2 mg/dL (unless history of Gilbert's disease)
Renal: No history of chronic renal insufficiency Creatinine less than 1.5 mg/dL OR
Creatinine clearance greater than 60 mL/min Cardiovascular: At least 6 months since
myocardial infarction No unstable angina No cardiac arrhythmias other than chronic atrial
fibrillation LVEF at least 50% Pulmonary: DLCO at least 50% Other: No medical illness that
would preclude study treatment No uncontrolled infection No history of malignancy, other
than curatively treated basal cell skin cancer or carcinoma in situ of the cervix Not
pregnant or nursing Fertile patients must use effective contraception Not HIV positive
PRIOR CONCURRENT THERAPY: No prior therapy