RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. Bone marrow or peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy to kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of high-dose chemotherapy followed by bone marrow or peripheral stem cell transplantation in treating patients with refractory Hodgkin's disease or non-Hodgkin's lymphoma.

OBJECTIVES: I. Determine the antitumor activity of intensive carmustine and etoposide with cisplatin or cyclophosphamide, followed by rescue with autologous bone marrow (ABM) treated in vitro with etoposide and/or peripheral blood stem cells mobilized with filgrastim (G-CSF) or sargramostim (GM-CSF) with or without radiotherapy in patients with refractory Hodgkin's disease or non-Hodgkin's lymphoma. II. Determine the time to recovery of peripheral blood counts in patients treated with this regimen. III. Correlate the rate of peripheral blood cell recovery in these patients with in vitro growth of ABM treated with etoposide.

PROTOCOL OUTLINE: This is a multicenter study. Autologous bone marrow (ABM) is harvested and two-thirds of the ABM is treated in vitro with etoposide (VP-16). ABM may have been stored earlier in the course of the disease for patients who are at high risk of relapse or who were previously treated with agents causing bone marrow or stem cell damage (e.g., nitrosoureas, pelvic irradiation). Patients with prior bone marrow involvement and subsequent bone marrow remission must have received 1 or 2 additional courses of the same chemotherapy before undergoing harvest of ABM. Patients for whom PBSC rescue alone is planned also undergo ABM harvest in case back-up ABM rescue is needed. Patients then receive sargramostim (GM-CSF) or filgrastim (G-CSF) subcutaneously beginning 5 days before harvest of peripheral blood stem cells (PBSC) and continuing until completion of harvest. Patients without extensive prior radiotherapy undergo radiotherapy to areas of measurable active disease plus a 2 cm margin on days -21 to -17 and -14 to -8. Patients without a contraindication to cisplatin (e.g., hearing impairment, peripheral neuropathy) receive cisplatin IV over 3 hours on days -7 to -3 and carmustine IV over 2 hours and VP-16 IV over 4 hours on days -6 to -4. Patients with a contraindication to cisplatin receive cyclophosphamide IV every 12 hours, VP-16 IV over 1 hour every 12 hours, and carmustine IV over 1 hour on days -7 to -4. ABM and/or PBSC are reinfused on day 0. The first 6 ABM rescue patients receive untreated ABM and subsequent patients receive ABM treated in vitro with VP-16. Patients with bone marrow biopsy showing no evidence of regeneration (marrow cellularity less than 1%) at day 21 after PBSC rescue undergo back-up ABM rescue. Patients without engraftment (granulocyte count less than 500/mm3 and untransfused platelets no greater than 20,000/mm3) by day 28 after rescue with ABM treated in vitro with VP-16 undergo rescue with untreated ABM.

PROJECTED ACCRUAL: A total of 21-46 patients will be accrued for this study.

Ages Eligible for Study:  15 Years   -   65 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Diagnosis of resistant Hodgkin's disease; Eligible subtypes: Lymphocytic predominance; Nodular sclerosing; Mixed cellularity; Lymphocyte depleted; Not otherwise specified; Must meet 1 of the following conditions: Disease progression after at least 1 course of prior therapy on each of 2 regimens comprising combination chemotherapy or radiotherapy; Less than a partial remission (PR) after at least 2 courses on each of 2 regimens; Failure to achieve a complete remission (CR) after 6 courses of 1 or 2 regimens; Relapse less than 1 year off initial therapy OR Diagnosis of intermediate- or high-grade non-Hodgkin's lymphoma (NHL); Eligible subtypes: Diffuse poorly differentiated lymphocytic; Diffuse mixed lymphocytic-histiocytic; Nodular histiocytic Diffuse histiocytic; Diffuse undifferentiated; Lymphoblastic; Must meet 1 of the following conditions: Disease progression after 1 course of prior therapy; Failure to achieve a PR after 2 courses of prior therapy; Failure to achieve a CR after 6 courses of prior therapy OR Diagnosis of low-grade NHL; Eligible subtypes: Diffuse well-differentiated lymphocytic; Nodular poorly differentiated lymphocytic ;Nodular mixed lymphocytic-histiocytic; Failure on second-line therapy administered for progressive symptomatic disease or organ compromise
• Measurable disease by physical exam, external imaging or scanning studies, or tumor markers
• No severe symptomatic CNS disease of any etiology; History of prior CNS tumor allowed if no signs or symptoms at study entry; Active CNS lymphoma (meningeal lymphomatosis) rendered disease-free by conventional therapies allowed Epidural metastases or discrete parenchymal brain lesions allowed if tumors can be encompassed in standard treatment fields
• Bilateral marrow core biopsy free of tumor and showing at least 30% cellularity
• Prior marrow involvement allowed if marrow is histologically normal at time of storage
• No significant skin breakdown due to tumor or other disease

[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.]

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: See Disease Characteristics; At least 4 weeks since prior chemotherapy (at least 6 weeks since prior nitrosoureas or mitomycin) Prior exposure to etoposide, cisplatin, or carmustine allowed if cumulative dose of chloroethylnitrosourea (carmustine or lomustine) no greater than 400 mg/m2; Prior doxorubicin or daunorubicin dose of 450 mg/m2 or more allowed if LVEF at least 50%; No concurrent chemotherapy
• Endocrine therapy: Concurrent corticosteroids for hypercalcemia allowed
• Radiotherapy: See Disease Characteristics; No prior whole-pelvic radiotherapy; Other prior radiotherapy allowed
• Surgery: Not specified
• Other: No concurrent nitroglycerin preparations for angina pectoris; No concurrent antiarrhythmic drugs for major ventricular arrhythmias

--Patient Characteristics--

• Age: 15 to 65
• Performance status: Karnofsky 70-100% OR ECOG 0-1
• Life expectancy: At least 8 weeks without transplantation
• Hematopoietic: Granulocyte count at least 1,500/mm3; Platelet count at least 150,000/mm3
• Hepatic: Bilirubin no greater than 1.8 mg/dL; SGOT and SGPT less than 2 times normal; No high risk for veno-occlusive disease of the liver
• Renal: No severe renal dysfunction unless due to tumor invasion; Creatinine no more than 1.5 mg/dL; Creatinine at least 60 mL/min
• Cardiovascular: No severe cardiovascular dysfunction unless due to tumor invasion; No myocardial infarction within the past 6 months; No symptoms of major heart disease; Ejection fraction at least 50% by MUGA scan; Essential hypertension controlled with medication allowed
• Pulmonary: No severe pulmonary dysfunction unless due to tumor invasion; DLCO at least 50% normal; No symptomatic obstructive or restrictive pulmonary disease
• Other: No insulin-dependent diabetes mellitus; No uncompensated major thyroid or adrenal dysfunction; No active infection; HTLV-III negative (no AIDS-related complex)