RATIONALE: Drugs used in chemotherapy use different ways to stop cancer 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 cancer cells. Monoclonal antibodies can locate cancer cells and either kill them or
deliver cancer-killing substances to them without harming normal cells.
PURPOSE: Phase II trial to study the effectiveness of peripheral stem cell transplantation
plus combination chemotherapy and rituximab in treating patients with non-Hodgkin's
OBJECTIVES: I. Evaluate the 1 and 2 year event free survival of patients with poor
prognosis, relapsed or refractory intermediate or high grade B-cell non-Hodgkin's lymphoma
who receive high dose carmustine and melphalan plus gemcitabine followed by rituximab
(IDEC-C2B8 monoclonal antibody; anti-CD20 monoclonal antibody) plus sargramostim and
consolidation chemotherapy with alternating dexamethasone/cyclophosphamide/
etoposide/cisplatin plus gemcitabine and paclitaxel/cisplatin and compare these figures to a
historical control population. II. Evaluate the ability of posttransplant rituximab therapy
in combination with sargramostim (GM-CSF) to control and further treat residual lymphoma
remaining after high dose therapy in these patients. III. Evaluate quality of life
parameters and assess the risk of secondary malignancies following this treatment regimen in
OUTLINE: Patients receive high dose gemcitabine IV over 100 minutes on day -5 and again
approximately 6 hours after carmustine IV over 2 hours on day -2. On day -1, patients
receive melphalan IV over 20 minutes followed 24 hours later (day 0) with peripheral blood
stem cells transplantation. Patients then receive sargramostim (GM-CSF) subcutaneously
beginning on day 4 until granulocyte count is greater than 1,000/mm3 for 2 consecutive days.
At weeks 5-8 posttransplant, patients receive rituximab (IDEC-C2B8 monoclonal antibody;
anti-CD20 monoclonal antibody) IV over 3-4 hours weekly. Prior to rituximab treatment at
week 4 posttransplant, patients receive sargramostim (GM-CSF) subcutaneously 3 times a week
continuing through rituximab therapy. At approximately 3 and 9 months posttransplant,
patients receive dexamethasone orally every day for days 1-4, and cyclophosphamide,
etoposide, and cisplatin by continuous infusion for 4 days (days 1-4), and gemcitabine IV
over 100 minutes on days 1 and 5. At approximately 6 and 12 months posttransplant, patients
receive paclitaxel IV over 6 hours on day 2 and cisplatin IV over 24 hours on day 3.
Patients are followed at least every 6 weeks to 3 months until death.
PROJECTED ACCRUAL: An estimated 25 patients per year will be accrued into this study.
DISEASE CHARACTERISTICS: Histologically confirmed intermediate or high grade B-cell
non-Hodgkin's lymphoma that meets one of the following criteria: - Relapsed or progressed
following at least 1 course of standard therapy - Developed from a low grade lymphoma
regardless of remission status - In first complete response with 3 or more of the
following pretreatment criteria met at the time of original diagnosis: Stage III/IV
disease Two or more extranodal sites of disease Lactate dehydrogenase greater than 1.2
times normal Performance status 2-4 (at time of diagnosis) Dimension of the largest tumor
at least 10 cm No myelodysplasia A new classification scheme for adult non-Hodgkin's
lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma
will replace the former terminology of "low", "intermediate", or "high" grade lymphoma.
However, this protocol uses the former terminology.
PATIENT CHARACTERISTICS: Age: 18 to 75 Performance status: See Disease Characteristics
ECOG 0-2 (ECOG 3-4 acceptable if based solely on pain) Life expectancy: Not specified
Hematopoietic: CD34 cells at least 1,000/g Hepatic: See Disease Characteristics Bilirubin
no greater than 1.5 mg/dL Transaminases no greater than 4 times upper limit of normal No
active chronic hepatitis or liver cirrhosis Renal: Creatinine no greater than 3.0 mg/dL
Cardiovascular: No evidence for clinically significant functional impairment Left
ventricular ejection fraction at least 45% Patients with lower ejection fractions may be
included if a formal cardiological evaluation reveals no evidence for clinically
significant functional impairment Pulmonary: FEV1, FVC, and DLCO at least 50% of predicted
If unable to complete pulmonary function tests due to bone pain or fracture, must have a
high resolution CT scan of the chest and acceptable blood arterial gases defined as PO2
greater than 70 Other: HIV negative No active infection that is unresponsive to
intravenous antibiotics Not pregnant or nursing Effective contraception required of all
PRIOR CONCURRENT THERAPY: See Disease Characteristics