Cyclophosphamide and Filgrastim in Treating Patients With Stage IV, Relapsed, or Refractory Low-Grade Follicular Non-Hodgkin's Lymphoma

OBJECTIVES: I. Determine the feasibility of high-dose cyclophosphamide and filgrastim
(G-CSF) in patients with stage IV, relapsed, or progressive low-grade follicular
non-Hodgkin's lymphoma. II. Determine the toxic effects of this regimen in these patients,
including those with marrow involvement. III. Determine the rates of complete remission (CR)
and partial remission and time to failure in previously treated and untreated patients. IV.
Determine the effectiveness of this regimen in eradicating bcl-2 rearrangements, as
determined by polymerase chain reaction (PCR), in previously untreated patients. V.
Correlate the duration of CR to PCR results in responding patients.

OUTLINE: Patients are stratified according to prior treatment (yes vs no). Patients receive
cyclophosphamide IV over 90 minutes on day 1 and filgrastim (G-CSF) subcutaneously beginning
on day 3 and continuing until blood counts recover. Treatment continues every 2 weeks for 4
courses in the absence of disease progression or stable disease. Patients who achieve
complete remission (CR) after completion of course 4 receive 2 additional courses. Patients
who achieve partial remission (PR) after completion of course 4 receive 2 additional
courses, and those who achieve CR after completion of course 6 receive 2 additional courses.
Patients are followed every 2 months for 6 months, every 6 months for 2 years, and then
annually thereafter.

DISEASE CHARACTERISTICS: Histologically proven low-grade non-Hodgkin's lymphoma of the
following subtypes: Follicular, predominantly small cleaved cell Follicular mixed (small
cleaved and large cell) Previously treated on Protocol CLB 8691 or previously untreated
Previously untreated patients with Stage IV disease (Ann Arbor classification) must meet
the following conditions: Documented bone marrow involvement Lymph node biopsy must not
show higher grade lymphoma At least 1 additional risk factor as follows: At least 2
extranodal sites Nodes or nodal group at least 5 cm Male Previously treated patients must
have progressed or relapsed on Protocol CLB-8691 Recurrence should be documented by biopsy
if possible Bidimensionally measurable disease by physical exam, radiograph, CT, or MRI
(sonography and barium studies alone not acceptable) Measurable liver disease defined as:
Mass greater than 3.5 cm on CT, MRI, or ultrasound OR Histologically documented
lymphomatous hepatomegaly more than 5 cm below the costal margin The following disease
manifestations are not considered measurable: Ascites or pleural effusion Bony disease
(lytic lesions on x-ray should be documented and followed) CNS lesions Bone marrow
involvement No lymphomatous involvement (including CNS lymphoma) requiring immediate
radiotherapy 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 physiologic 55 Patients over 55 are eligible only if
study chairperson agrees that the patient can tolerate intensive chemotherapy Performance
status: Zubrod 0-1 Life expectancy: More than 2 years Hematopoietic: Granulocyte count at
least 1,500/mm3 Platelet count at least 100,000/mm3 Hemoglobin at least 9.0 g/dL Hepatic:
Bilirubin less than 1.5 times normal Renal: Creatinine less than 1.5 times normal
Cardiovascular: LVEF at least 50% No acute changes or arrhythmias on ECG No cardiomegaly
on chest x-ray or physical exam No uncontrolled or severe cardiovascular disease,
including myocardial infarction within the past 6 months or congestive heart failure (CHF)
No active cardiac problems, including compensated CHF or angina Other: HIV negative No
other malignancy within the past 5 years except curatively treated basal cell skin cancer
or carcinoma in situ of the cervix No active uncontrolled bacterial, viral, or fungal
infection No other serious medical illness that would limit survival to less than 2 years
No psychiatric condition that would preclude informed consent or compliance No
uncontrolled duodenal ulcer Not pregnant Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: Prior interferon only on Protocol CLB-8691
allowed Chemotherapy: Prior oral cyclophosphamide only on Protocol CLB-8691 allowed No
concurrent chemotherapy Endocrine therapy: No chronic steroids for other health problems
No concurrent steroids for any condition including documented CNS metastases, adrenal
failure, or septic shock Nonsteroidal hormonal drugs for nondisease related problems
allowed (e.g., insulin for diabetes) Radiotherapy: See Disease Characteristics No prior
radiotherapy No concurrent palliative radiotherapy Surgery: At least 2 weeks since prior
major surgery Other: No other prior therapy