Malignant neoplasms in long-term survivors of bone marrow transplantation. Late Effects Working Party of the European Cooperative Group for Blood and Marrow Transplantation and the European Late Effect Project Group

Ann Intern Med. 1999 Nov 16;131(10):738-44. doi: 10.7326/0003-4819-131-10-199911160-00004.


Background: Patients who receive bone marrow transplants have increased risk for new malignant conditions because of several risk factors, including conditioning with radiation and chemotherapy, immune stimulation, and malignant primary disease. The occurrence of and risk factors for malignant neoplasm in long-term survivors must be assessed.

Objective: To determine the risk and define potential risk factors for new malignant conditions in long-term survivors after marrow transplantation.

Design: Retrospective multicenter study.

Setting: Study of the Late Effects Working Party with 45 transplantation centers cooperating in the European Cooperative Group for Blood and Marrow Transplantation.

Patients: 1036 consecutive patients who underwent transplantation for leukemia, lymphoma, inborn diseases of the hematopoietic and immune systems, or severe aplastic anemia. Transplantation was done before December 1985, and patients had survived more than 5 years.

Measurements: Reports on malignant neoplasms were evaluated, and the incidence was compared to that in the general population. Patient age and sex, primary disease and status at transplantation, histocompatibility of the donor, conditioning regimen, type of prophylaxis of graft-versus-host disease, development of acute and chronic graft-versus-host disease, and treatment of chronic graft-versus-host disease were evaluated as variables.

Results: Median follow-up since transplantation was 10.7 years (range, 5 to 22.1 years). Malignant neoplasms were seen in 53 patients; the actuarial incidence (+/- SE) was 3.5% +/- 0.6% at 10 years and 12.8% +/- 2.6% at 15 years. The rate of new malignant disease was 3.8-fold higher than that in an age-matched control population (P < 0.001). The most frequent malignant diseases were neoplasms of the skin (14 patients), oral cavity (7 patients), uterus (including cervix) (5 patients), thyroid gland (5 patients), breast (4 patients), and glial tissue (3 patients). Median age of patients and their donors was 21 years. Malignant neoplasms were more frequent in older patients and in patients with chronic graft-versus-host disease. Older patient age and treatment of chronic graft-versus-host disease with cyclosporine were significant risk factors for new malignant neoplasms after bone marrow transplantation.

Conclusions: The spectrum of neoplasms and immunosuppressive treatment with cyclosporine for chronic graft-versus-host disease as dominant risk factors indicate that immunosuppression is the major cause of malignant neoplasms in patients receiving marrow transplants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Analysis of Variance
  • Anemia, Aplastic / therapy
  • Bone Marrow Transplantation*
  • Child
  • Cyclosporine / adverse effects
  • Cyclosporine / therapeutic use
  • Female
  • Graft vs Host Disease / drug therapy
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use
  • Leukemia / therapy
  • Male
  • Neoplasms, Second Primary / etiology*
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Factors
  • Survival Analysis
  • Time Factors


  • Immunosuppressive Agents
  • Cyclosporine