title: Late non-neoplastic events in patients with aggressive non-Hodgkin's lymphoma in four randomized European Organisation for Research and Treatment of Cancer trials.
abstract: BACKGROUND
  A significant proportion of patients with aggressive non-Hodgkin's lymphoma (NHL) become long-term survivors. A European Organisation for Research and Treatment of Cancer database of patients with aggressive NHL, consistently treated with doxorubicin-based chemotherapy since 1980, afforded the possibility to explore late complications in this patient group.
  
  
  METHODS
  Of 951 randomized patients, complete data on late complications could be collected in 757 patients who were alive > or = 2 years after the start of therapy and were seen at yearly follow-ups (median follow-up, 9.4 years; range, 2.1-20.4 years). We computed cumulative incidences of late events in a competing risk model by Gray (death being the competing event) to avoid bias caused by the high percentage of NHL-related deaths. Risk factors were estimated in a Cox proportional-hazards model and also evaluated with the Gray test.
  
  
  RESULTS
  Late non-neoplastic events were found in 46% of the 757 patients. At 15 years, the cumulative incidences of cardiac disease and infertility were 20% and 29%, respectively. Renal insufficiency (11%), acquired hypertension (8%), and disabling neuropathy (13%) were also frequent. Salvage treatment was a risk factor in most cases. Smoking, age > 50 years during treatment, and preexistent hypertension were the main risk factors for cardiovascular disease. In-field radiation therapy (RT) was related to hypothyroidism, lung fibrosis, hypertension, gastrointestinal toxicity, and renal insufficiency but not to cardiovascular events. Autologous stem cell transplantation and cisplatin- and MOPP (mechlorethamine/vincristine/procarbazine/prednisone)-containing therapies were associated with infertility and renal insufficiency.
  
  
  CONCLUSIONS
  Altogether, almost half the patients with aggressive NHL experienced events addressed as late non-neoplastic complications. Salvage therapy, smoking, age > 50 years, and in-field RT are important risk factors.
authors.affiliation: European Organisation for the Research and Treatment of Cancer Data Center, Brussels, Belgium.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Moser
authors.forename: Evert M
authors.initials: EM
authors.lastname: Noordijk
authors.forename: Patrice
authors.initials: P
authors.lastname: Carde
authors.forename: Umberto
authors.initials: U
authors.lastname: Tirelli
authors.forename: Joke W
authors.initials: JW
authors.lastname: Baars
authors.forename: Jose
authors.initials: J
authors.lastname: Thomas
authors.forename: Dominique
authors.initials: D
authors.lastname: Bron
authors.forename: Jacobus H
authors.initials: JH
authors.lastname: Meerwaldt
authors.forename: Martine
authors.initials: M
authors.lastname: van Glabbeke
authors.forename: John M M
authors.initials: JM
authors.lastname: Raemaekers
authors.forename: Hanneke C
authors.initials: HC
authors.lastname: Kluin-Nelemans
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000150:complications* / Q000401:mortality / Q000628:therapy; D008297:Male; D008466:Mechlorethamine / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D011344:Procarbazine / Q000009:adverse effects / Q000627:therapeutic use; D011878:Radiotherapy / Q000009:adverse effects; D012307:Risk Factors; D016879:Salvage Therapy / Q000009:adverse effects* / Q000401:mortality; D012907:Smoking / Q000009:adverse effects; D012955:Societies, Medical; D033581:Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000401:mortality; D014182:Transplantation, Autologous; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D011344:Procarbazine; D008466:Mechlorethamine; D014750:Vincristine; D011241:Prednisone