High-Dose Chemo-Radiotherapy for Patients With Primary Refractory and Relapsed Hodgkin's Disease

OBJECTIVES: Assess the efficacy of a high-dose chemoradiotherapy regimen in patients with refractory or relapsed Hodgkin's lymphoma. OUTLINE: Patients are stratified into 1 of 3 treatment arms (0-1 adverse prognostic factors vs 2 adverse prognostic factors vs 3 adverse prognostic factors). Arm I (0-1 adverse prognostic factors): Patients receive ifosfamide by 24 hour infusion on day 2. Carboplatin is administered on day 2. Etoposide IV is administered once daily on days 1-3. Patients then receive filgrastim (G-CSF) subcutaneously or IV on days 5-12. Patients receive another course of ICE chemotherapy 2-3 weeks after the first course. Leukapheresis is performed once WBC reaches at least 3000/mm^3 and continues until enough peripheral blood stem cells are collected. Patients who have never received prior radiotherapy will receive accelerated hyperfractionated total lymphoid irradiation (TLI) twice a day for 5 days (days -10 to -6). Cyclophosphamide IV is then administered on days -5 and 4. Etoposide IV is administered by continuous infusion over 4 days (days -5 to -2). Patients who have had prior radiotherapy receive high dose chemotherapy. Cyclophosphamide IV is administered on days -6 and -5. Etoposide IV is administered by continuous infusion over 4 days (days -6 to -3). Carmustine IV is administered on day -2. Peripheral blood stem cells are infused 24-36 hours after high-dose chemotherapy. G-CSF is administered beginning on day 1 and continuing until blood counts recover. Arm II (2 adverse prognostic factors): Patients receive the first course of ICE as in Arm I. Apheresis is performed once WBC is greater than 3000/mm^3 and continues until enough cells are collected. The second course of ICE is then administered. Ifosfamide is administered by 48 hour continuous infusion on days 1-2. Carboplatin is administered on day 3. Etoposide IV is administered every 12 hours for 3 doses beginning on day 1. Patients receive G-CSF on days 5-14. Patients who have never received prior radiotherapy will receive accelerated hyperfractionated TLI for 5 days (days -10 to -6). Cyclophosphamide IV is then administered every 12 hours on days -5 to -2. Etoposide IV is administered by continuous infusion over 4 days (days -5 to -2). Patients who have had prior radiotherapy receive high-dose chemotherapy. Cyclophosphamide IV is administered every 12 hours on days -6 to -3. Etoposide IV is administered by continuous infusion over 4 days (days -6 to -3). Carmustine IV is administered on day -2. Peripheral blood stem cells are infused 24-36 hours after high dose chemotherapy. G-CSF is administered beginning on day 1 and continuing until blood counts recover. Arm III (3 adverse prognostic factors): Patients receive cyclophosphamide IV daily for 2 days, then G-CSF beginning on day 4 until blood stem cells are collected. Patients then undergo apheresis until enough cells are collected. Patients receive high-dose chemotherapy. Ifosfamide IV is administered for 1 hour. Etoposide is administered by continuous infusion for 12 hours. Carboplatin IV is administered for 1 hour. Etoposide is again administered by continuous infusion for 12 hours. Treatment is repeated daily for 5 days. Peripheral blood stem cells are reinfused 24-36 hours after the last dose of chemotherapy. G-CSF is administered beginning on day 1 and continuing until blood counts recover. Patients who have never received prior radiation will now receive accelerated hyperfractionated TLI twice daily for 5 days. Patients receive a second course of high dose chemotherapy 45-90 days after reinfusion of cells. Etoposide IV and cytarabine IV are administered every 12 hours for 4 days (days -6 to -3). Melphalan IV is administered on day -2. Patients who have received prior radiation therapy receive a second course of high-dose chemotherapy. Carmustine IV is administered on day -7. Etoposide IV and cytarabine IV are administered every 12 hours for 4 days (days -6 to -3). Melphalan IV is administered on day -2. Peripheral blood stem cells are reinfused 24-48 hours after completion of second course chemotherapy. G-CSF is administered beginning on day 1 and continuing until blood counts recover. Patients are followed every 3 months for the first 2 years, every 4 months during years 3-5, and every 6 months thereafter. PROJECTED ACCRUAL: This study will accrue 80 patients within 4 years.