Malignant neoplasms in long-term survivors of bone marrow transplantation

Background: Patients who receive bone marrow transplants have increased ris k for new malignant conditions because of several risk factors, including c onditioning with radiation and chemotherapy, immune stimulation, and malign ant primary disease. The occurrence of and risk factors for malignant neopl asm 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 ce nters cooperating in the European Cooperative Group for Blood and Marrow Tr ansplantation. Patients: 1036 consecutive patients who underwent transplantation for leuke mia, 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 incide nce was compared to that in the general population. Patient age and sex, pr imary disease and status at transplantation, histocompatibility of the dono r, conditioning regimen, type of prophylaxis of graft-versus-host disease, development of acute and chronic graft-versus-host disease, and treatment o f 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 i ncidence (+/- SE) was 3.5% +/- 0.6% at 10 years and 12.8% +/- 2.6% at 15 ye ars. 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 dis eases were neoplasms of the skin (14 patients), oral cavity (7 patients), u terus (including cervix) (5 patients), thyroid gland (5 patients), breast ( 4 patients), and glial tissue (3 patients). Median age of patients and thei r donors was 21 years. Malignant neoplasms were more frequent in older pati ents and in patients with chronic graft-versus-host disease. Older patient age and treatment of chronic graft-versus-host disease with cyclosporine we re significant risk factors for new malignant neoplasms after bone marrow t ransplantation. Conclusions: The spectrum of neoplasms and immunosuppressive treatment with cyclosporine for chronic graft-versus-host disease as dominant risk factor s indicate that immunosuppression is the major cause of malignant neoplasms in patients receiving marrow transplants.