High‐dose chemo‐radiotherapy for relapsed or refractory Hodgkin lymphoma and the significance of pre‐transplant functional imaging

We previously reported that three risk factors (RF): initial remission duration <1 year, active B symptoms, and extranodal disease predict outcome in relapsed or refractory Hodgkin lymphoma (HL). Our goal was to improve event‐free survival (EFS) for patients with multiple RF and to determine if response to salvage therapy impacted outcome. We conducted a phase II intent‐to‐treat study of tailored salvage treatment: patients with zero or one RF received standard‐dose ifosfamide, carboplatin, and etoposide (ICE); patients with two RF received augmented ICE; patients with three RF received high‐dose ICE with stem cell support. This was followed by evaluation with both computed tomography and functional imaging (FI); those with chemosensitive disease underwent high‐dose chemoradiotherapy and autologous stem cell transplantation (ASCT). There was no treatment‐related mortality. Compared to historical controls this therapy eliminated the difference in EFS between the three prognostic groups. Pre‐ASCT FI predicted outcome; 4‐year EFS rates was 33% vs. 77% for patients transplanted with positive versus negative FI respectively, P = 0·00004, hazard ratio 4·61. Risk‐adapted augmentation of salvage treatment in patients with HL is feasible and improves EFS in poorer‐risk patients. Our data suggest that normalisation of FI pre‐ASCT predicts outcome, and should be the goal of salvage treatment.