Risk of second primary cancers after Hodgkin's disease by type of treatment: analysis of 2846 patients in the British National Lymphoma Investigation

BMJ. 1992 May 2;304(6835):1137-43. doi: 10.1136/bmj.304.6835.1137.


Objective: To analyse the risk of second primary cancers during long term follow up of patients with Hodgkin's disease.

Design: Cohort study.

Setting: The British National Lymphoma Investigation (a collaborative group of over 60 participating centres in Britain treating lymphomas).

Patients: 2846 patients first treated for Hodgkin's disease during 1970-87, for whom follow up was complete in 99.8%.

Main outcome measures: Second primary cancers; uniform pathology reviews confirmed the diagnosis of Hodgkin's disease and of second primary non-Hodgkin's lymphomas.

Results: 113 second primary cancers occurred. Relative risk of cancer other than Hodgkin's disease was 2.7 (95% confidence interval 2.3 to 3.3) compared with the general population, with significant risk of leukaemia (16.0(9.1 to 26.0)); non-Hodgkin's lymphoma (16.8(9.8 to 26.9)); and cancers of the colon (3.2 (1.4 to 6.2)), lung (3.8 (2.6 to 5.4)), bone (15.1 (1.8 to 54.7)), and thyroid (9.4 (1.1 to 33.9)). Absolute excess risk associated with treatment was greater for solid tumours than for leukaemia and lymphomas. Relative risk of leukaemia increased soon after treatment, reaching a peak after five to nine years. It was increased substantially after chemotherapy (27.9 (12.7 to 52.9)), combined treatment with radiotherapy and chemotherapy (21.5 (7.9 to 46.8)), and relative to number of courses of chemotherapy but was not significantly increased after radiotherapy (2.5 (0.1 to 14.1)). Relative risk of non-Hodgkin's lymphoma increased in the first five years after treatment and remained high but showed no clear relation with type or extent of treatment. Relative risk of solid tumours was less raised initially but increased throughout follow up and for lung cancer 10 years or more after entry was 8.3 (4.0 to 15.3). The risk of solid tumours increased after treatments including radiotherapy and after chemotherapy alone. The risk after chemotherapy increased significantly with time since first treatment.

Conclusion: The risk of solid cancer, not of leukaemia, is the major long term hazard of treatment for Hodgkin's disease, and this seemed to apply after chemotherapy as well as after radiotherapy. These risks of second cancers are important in choice of treatment and in follow up of patients, but they are small compared with the great improvements in survival which have been brought about by modern therapeutic methods for Hodgkin's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alkylating Agents / adverse effects
  • Child
  • Chlorambucil / adverse effects
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Hodgkin Disease / therapy*
  • Humans
  • Male
  • Mechlorethamine / adverse effects
  • Neoplasms, Second Primary / epidemiology*
  • Neoplasms, Second Primary / etiology*
  • Radiotherapy / adverse effects
  • Risk
  • Risk Factors
  • Time Factors
  • United Kingdom


  • Alkylating Agents
  • Chlorambucil
  • Mechlorethamine