Combination 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.

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.

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.

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)

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