Risk-Adpated High Dose Chemoradiotherapy and ASCT

403] Risk-Adpated High Dose Chemoradiotherapy and ASCT for Patients with Relapsed and Primary Refractory Hodgkin s Disease: An Intent to Treat Analysis. Session Type: Oral Session Craig H. Moskowitz, Tarun Kewalramani, Stephen D. Nimer, Robert D. Rice, Lisa Rosenzweig, Steven Horwitz, Ariela Noy, Owen O Connor, Carol S. Portlock, David Straus, Tanya Tripett, Andrew D. Zelenetz, Joachim Yahalom Medicine, Memorial Sloan Kettering Cancer Center, NY, NY, USA; Radiation Oncology, Memorial Sloan Kettering Cancer Center, NY, NY, USA

Event-free survival (EFS) with high dose chemoradiotherapy (HDT) and ASCT for patients (pts) with relapsed or primary refractory Hodgkin s Disease (HD) is 40-45%. In our previous study of 81 pts receiving 2 courses of ifosfamide, carboplatin and etoposide (ICE) followed by involved field radiotherapy (IFRT) and HDT (cyclophosphamide (c) , etoposide (e) and either total lymphoid radiation (TLI) or carmustine (b)) and ASCT the 6 yr. EFS is 54%. Three risk factors (RFs) predicted survival: extranodal disease pre-ICE, B symptoms pre-ICE and initial remission duration < 1 yr. The EFS for pts with 0-1, 2 or 3 RFs are 76%, 36% and 8% respectively (p<0.0001)(Blood 97: 616-623, 2001). We now report the results of a second intent to treat program of 92 pts treated in a risk adapted approach based upon these 3 RFs. There are 43 pts with 0-1 RF, ARM A, and they were treated as in program 1. There are 37 pts with 2 RFs (ARM B); treated with augmented ICE (I-10,000 mg/m2, C 300 mg/m2 and E 600 mg/m2) with responders receiving a higher dose transplant conditioning regimen (c-7200 mg/m2, e-2000 mg/m2, b-360 mg/m2). Pts with all 3 RFs (ARM C) received transplant doses of ICE (I-15000 mg/m2 C-1500 mg/m2, E-1500 mg/m2) with PBPC support followed by a second autotransplant or allotransplant if chemosensitive disease was achieved. The median follow-up of the surviving pts is 32 months. There was no transplant related mortality. ARM A included 16 pts with no RFs and 27 pts with one RF. Forty-one pts (95%) responded to ICE; 31 pts received IFRT pre-ASCT and 19 pts received a TLI-based conditioning regimen. The EFS and overall survival (OS) of ARM A is 70% and 85% respectively. ARM B included 33/37 pts with remission duration of < 1 yr; 12/37 with active B symptoms and 30/37 with extranodal disease. Thirty-one pts (84%) had chemosensitive disease to augmented ICE; 19 received IFRT and 12 pts received a TLI-based conditioning regimen. The EFS and OS of ARM B is 46% and 66% respectively. ARM C included 12 pts. Five patients received 1 transplant: one progressed after high dose ICE and 4 pts had an inadequate PBPC collection. Seven pts received a second transplant. The EFS and OS of ARM C is 45% and 82% respectively. The second program compares favorably to program 1 for patients with 2 or 3 RFs with an EFS of 45% vs 27% for program 1 (p= 0.07). Abnormal functional imaging (FI) (PET or gallium scan) pre-ASCT was the strongest predictor for EFS in the 82 transplanted pts. Pts with abnormal FI pre-ASCT had an EFS of 40% vs 76% for those with normal FI pre-ASCT (p <0.0001); all transplanted pts had an EFS of 64.3%. Abnormal FI pre-ASCT was most prognostic for pts with favorable RFs, ARM A, where the EFS was 25% vs 85% for pts with normal FI pre-ASCT (p < 0.0001).Conclusion: Risk adapted therapy for relapsed or primary refractory HD is well tolerated and may improve outcome for pts with adverse prognostic features. Pts with normal FI pre-ASCT have a very favorable outcome. Our current effort is focused on pts with 0-2 RFs and abnormal FI post-ICE. These pts may benefit from the incorporation of novel agents into the ICE program as well as more intensive radiation (intensity modulated RT). The results of tandem transplants in patients with 3 RFs appear promising though confirmation requires testing in a larger multicenter setting.Abstract #403 appears in Blood, Volume 102, issue 11, November 16, 2003Keywords: Hodgkin s Disease|relapsed/refractory|risk-adaptedMonday, December 8, 2003 11:00 AM