High-Dose Chemotherapy in Treating Patients Undergoing Stem Cell Transplant for Recurrent or Refractory Hodgkin's Lymphoma

OBJECTIVES:

• To evaluate the feasibility and toxicity of high-dose sequential therapy comprising high-dose etoposide and cyclophosphamide with filgrastim (G-CSF) support followed by 2 courses of high-dose therapy and autologous stem cell transplantation in patients with poor-risk recurrent or refractory Hodgkin lymphoma.
• To analyze the response rate, progression-free survival, and overall survival of patients treated with this regimen.
• To determine the percentage of patients who can achieve a minimal disease status after two courses of Hodgkin lymphoma chemotherapy and before "classical autologous stem cell transplantation."

OUTLINE:

• First high-dose chemotherapy*: Patients receive high-dose cyclophosphamide IV over 2 hours followed by etoposide IV over 4 hours.

NOTE: *Patients with minimal disease (i.e., a single lymph node ≤ 2 cm in maximal horizontal diameter or a > 75% reduction in a bulky (≥ 10 cm) tumor mass AND no morphological evidence of active bone marrow disease) at initial evaluation do not receive the first high-dose chemotherapy but proceed directly to peripheral blood stem cell (PBSC) mobilization with filgrastim (G-CSF) for 3 days and PBSC collection beginning on day 4.

• Peripheral stem cell mobilization and collection: Patients receive G-CSF subcutaneously beginning 96 hours after completion of etoposide and continuing through completion of PBSC collection. Patients undergo leukapheresis to collect PBSC for reinfusion after additional high-dose therapy.
• Second high-dose chemotherapy: Patients receive high-dose melphalan IV over 30 minutes on day -1.
• First PBSC infusion: At least 24 hours after completion of melphalan, patients undergo reinfusion of PBSC on day 0.
• Local radiotherapy: Patients with a localized tumor mass > 5 cm after the second course of chemotherapy or a previous history of bulky disease (> 10 cm or mediastinal mass > 1/3 of transverse thoracic diameter) that has not been irradiated may receive local radiotherapy for 2 weeks, at the discretion of the principal investigator.
• High-dose therapy: Eight to 12 weeks after completion of the second course of chemotherapy, patients receive 1 of 2 regimens.

• Regimen A: Patients undergo fractionated total body irradiation 3 times daily on days -8 to -5 (10 fractions) and receive high-dose etoposide IV over 4 hours on day -4 and cyclophosphamide IV on day -2.
• Regimen B: Patients receive high-dose carmustine IV over 4 hours on days -7 to -5 and etoposide and cyclophosphamide as in regimen A.
• Second PBSC infusion: At least 48 hours after completion of cyclophosphamide, patients undergo reinfusion of PBSC on day 0.

After completion of study therapy, patients are followed at day 60 and then every 3 months for up to 1 year.

DISEASE CHARACTERISTICS:

• Histologically confirmed Hodgkin lymphoma

• Diagnosis reviewed by the participating institution
• Failed to achieve complete remission (CR) after first-line chemotherapy or chemoradiotherapy (i.e., induction failure) OR not felt to be curable by radiotherapy alone
• Relapsed after standard chemotherapy regimen for Hodgkin lymphoma AND has ≥ 1 of the following poor-risk features:

• Extranodal disease at relapse
• Interval from first CR to relapse < 12 months
• B symptoms at relapse
• Chemo-resistant relapse OR failure to achieve a second CR with conventional nontransplantation salvage chemotherapy regimen
• No cytogenetic abnormality on cytogenetic analysis of bone marrow

PATIENT CHARACTERISTICS:

Inclusion criteria

• SWOG performance status 0-1
• LVEF > 50% by 2D-ECHO or MUGA scan

• Patients with LVEF between 45-50% and without wall motion abnormalities are assessed on an individual basis after consultation with the cardiologist
• FEV_1 or DLCO > 45% predicted
• Creatinine clearance > 60 mL/min
• HIV-negative
• Hepatitis B surface antigen-negative
• Hepatitis C virus-negative
• ALT ≤ 5 times upper limit of normal
• No inadequate vital organ function
• No active infection
• Fertile patients must use adequate contraception

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Concurrent, post-transplantation, consolidative radiotherapy to residual masses allowed provided the patient has engrafted with a WBC > 4,000/μL and a platelet count > 100,000/μL