Outcome of Patients With Early-Stage Infradiaphragmatic Hodgkin Lymphoma: A Comprehensive Analysis From the German Hodgkin Study Group

J Clin Oncol. 2018 Sep 1;36(25):2603-2611. doi: 10.1200/JCO.2018.78.7192. Epub 2018 Jul 10.


Purpose The prognostic effect of isolated infradiaphragmatic involvement in Hodgkin lymphoma (HL) is controversial, and there are little data about patients treated with current therapies. Therefore, we performed a risk factor analysis to focus on isolated nodal infradiaphragmatic disease in patients treated within the German Hodgkin Study Group trials HD13 (clinical trial information: ISRCTN63474366) and HD14 (clinical trial information: ISRCTN04761296) for early-stage HL. Patients and Methods Characteristics and outcomes of patients who had infradiaphragmatic HL were compared with patients who had supradiaphragmatic disease. Progression-free survival (PFS) and overall survival (OS) were estimated according to Kaplan-Meier methods and were compared between groups using the log-rank test and Cox proportional hazards regression, which was also applied for multivariable analyses that adjusted for relevant baseline characteristics. Results Of 2,903 qualified patients, 223 (7.7%) were diagnosed with isolated nodal infradiaphragmatic disease. In general, these patients were older, had a poorer performance status, were more often male, and had the nodular sclerosis subtype less often than those with supradiaphragmatic disease. After a median follow-up time of 51 months, PFS and OS were significantly worse in patients with infradiaphragmatic disease (5-year PFS and OS, 80.1% and 91.5% v 91.2% and 97.6% in patients with supradiaphragmatic disease; each P < .001). In multivariable analyses, infradiaphragmatic HL remained a significant risk factor in terms of PFS (hazard ratio [HR], 1.5; 95% CI, 1.04 to 2.2; P = .03) and OS (HR, 2.0; 95% CI, 1.2 to 3.5; P = .01). However, inferior PFS and OS could not be observed among those patients treated with the more intensive chemotherapy (two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine [ABVD] in HD13, and two cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone [BEACOPPescalated] plus two cycles of ABVD in HD14; all patients received 30 Gy of involved-field radiotherapy). Conclusion Early-stage HL that presents with infradiaphragmatic disease only represents a distinct patient group with an inferior outcome. However, this adverse outcome can be outweighed by appropriate combined modality treatment.

Trial registration: ClinicalTrials.gov NCT00265018.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bleomycin / administration & dosage
  • Bleomycin / adverse effects
  • Chemoradiotherapy / methods*
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Dacarbazine / administration & dosage
  • Dacarbazine / adverse effects
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Etoposide / administration & dosage
  • Etoposide / adverse effects
  • Female
  • Hodgkin Disease / mortality
  • Hodgkin Disease / pathology*
  • Hodgkin Disease / therapy*
  • Humans
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis / pathology*
  • Male
  • Middle Aged
  • Prednisone / administration & dosage
  • Prednisone / adverse effects
  • Procarbazine / administration & dosage
  • Procarbazine / adverse effects
  • Progression-Free Survival
  • Treatment Outcome
  • Vincristine / administration & dosage
  • Vincristine / adverse effects
  • Young Adult


  • Bleomycin
  • Procarbazine
  • Vincristine
  • Etoposide
  • Dacarbazine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone

Associated data

  • ISRCTN/ISRCTN63474366
  • ISRCTN/ISRCTN04761296
  • ClinicalTrials.gov/NCT00265018