Background
Retrospective analysis of 471 patients with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) enrolled in GHSG trials HD7 through HD15 (1993–2003). NLPHL is a distinct entity from classical HL, characterized by LP ("popcorn") cells expressing CD20 but not CD30 in a follicular dendritic meshwork background. Treatment varied by stage: stage IA received involved-field RT; higher stages received ABVD-based or escalated BEACOPP ± RT per trial. A complementary analysis of 256 stage IA patients appears in JCO 2015.
Interventions and follow up
Regimen: Retrospective pooled analysis of NLPHL patients enrolled in GHSG HD7–HD15 trials treated with stage-adapted strategies (RT alone, ABVD±RT, escalated BEACOPP±RT)
Primary endpoint: Retrospective analysis — long-term PFS and OS by GHSG trial era
Median follow up: 10 years
Primary endpoint: Retrospective analysis — long-term PFS and OS by GHSG trial era
Median follow up: 10 years
Results
10-yr PFS (all stages): 75.5%
10-yr OS (all stages): 92.1%
Stage IA (JCO 2015, n=256): 8-yr PFS with IF-RT 91.9% vs. rituximab monotherapy 81.0% at 4 years — IF-RT superior
Transformation to aggressive B-cell lymphoma: 7.9% at 10 years
HD16/HD17 subanalysis (Blood 2023): RT omission after 2×ABVD in early favorable NLPHL — 5-yr PFS 83% (no RT) vs. 100% (RT), P=.05
10-yr OS (all stages): 92.1%
Stage IA (JCO 2015, n=256): 8-yr PFS with IF-RT 91.9% vs. rituximab monotherapy 81.0% at 4 years — IF-RT superior
Transformation to aggressive B-cell lymphoma: 7.9% at 10 years
HD16/HD17 subanalysis (Blood 2023): RT omission after 2×ABVD in early favorable NLPHL — 5-yr PFS 83% (no RT) vs. 100% (RT), P=.05
Adverse events
RT-related late effects: secondary malignancies and cardiovascular events are the major concern for patients cured with IF-RT
Chemotherapy-related: ABVD pulmonary/cardiac toxicity in advanced-stage patients
Disease-related: histologic transformation to DLBCL (~8% at 10 years) is the dominant cause of disease-related mortality; NLPHL has a slower, protracted relapse pattern with late relapses (beyond 5 years) common
Chemotherapy-related: ABVD pulmonary/cardiac toxicity in advanced-stage patients
Disease-related: histologic transformation to DLBCL (~8% at 10 years) is the dominant cause of disease-related mortality; NLPHL has a slower, protracted relapse pattern with late relapses (beyond 5 years) common
Conclusions
Long-term analysis of 471 NLPHL patients demonstrated 10-year PFS of 75.5% and OS of 92.1%, with IF-RT achieving excellent stage IA outcomes (8-yr PFS 91.9%). The ~8% risk of histologic transformation to aggressive B-cell lymphoma is a key late event requiring surveillance. IF-RT remains the standard for stage IA NLPHL.
Key Limitations
Retrospective pooled analysis across heterogeneous protocols and eras (1993–2003), with treatment not randomized by histology — NLPHL patients were enrolled on cHL-designed trials, so regimens were not optimized for NLPHL biology. Modern PET staging, rituximab-based strategies, and active surveillance were not uniformly applied. The slow relapse pattern means even 10-year follow-up may underestimate late events and transformation. The stage IA rituximab comparison (JCO 2015) used short follow-up (4 yr) versus longer RT data.
Clinical Context
This GHSG dataset anchors the modern approach to NLPHL: limited-field RT alone for stage IA, with chemotherapy (± rituximab, given CD20 positivity) reserved for advanced or transformed disease. Active surveillance after complete excision is increasingly used in select limited-stage cases. ESMO and GHSG/SIOPE guidance recognize NLPHL as a distinct entity warranting de-escalated, B-cell–directed management. Subsequent GHSG HD16/HD17 and surveillance cohorts continue to refine RT omission.