High-dose chemotherapy and autologous stem-cell transplant (HDC/ASCT) is standard treatment of chemosensitive relapsed classical Hodgkin lymphoma (cHL), although outcomes of high-risk relapse (HRR) patients remain suboptimal. We retrospectively analyzed all HRR cHL patients treated with HDC/ASCT at our institution between 01/01/2005-12/31/2019. HRR criteria included primary refractory disease/relapse within 1 year, extranodal extension, B symptoms, requiring > 1 salvage line, or PET+ disease at ASCT. All patients met the same ASCT eligibility criteria. We treated 501 patients with BEAM (N=146), BuMel (N=38), GemBuMel (N=189) and vorinostat/GemBuMel (N=128). The GemBuMel and vorinostat/GemBuMel cohorts had more HRR criteria and more patients with PET+ disease at ASCT. Pre-ASCT BV, anti-PD1, PET-negative disease at ASCT, and maintenance BV increased over time. BEAM and BuMel predominated in earlier years (2005-2007), GemBuMel and BEAM in middle years (2008-2015), and vorinostat/GemBuMel and BEAM in later years (2016-2019). Median follow-up is 50 months (6-186). Outcomes improved over time, with 2-year PFS/OS rates of 58%/82% (2005-2007), 59%/83% (2008-2011), 71%/94% (2012-2015) and 86%/99% (2016-2019) (P<0.0001). Five-year PFS/OS rates after vorinostat/GemBuMel were 72%/87%, GemBuMel: 55%/75%, BEAM: 45%/61%, BuMel: 39%/57% (PFS: P=0.0003; OS: P<0.0001). These differences persisted within the PET- and PET+ subgroups. Prior BV and vorinostat/GemBuMel were independent favorable predictors, whereas primary refractory disease, ≥2 salvage lines, bulky relapse, B symptoms and PET+ at ASCT correlated independently with unfavorable outcome. In conclusion, post- HDC/ASCT outcomes of HRR cHL patients have improved over the last 15 years. Pre-ASCT BV and optimized synergistic HDC (vorinostat/GemBuMel) were associated with this improvement.
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