H. J. Kolb, MD, PhD; Gérard Socié, MD, PhD; Thomas Duell, MD; Maria Theresa Van Lint, MD; André Tichelli, MD; Jane F. Apperley, MD; Elke Nekolla, PhD; Per Ljungman, MD, PhD; Niels Jacobsen, MD, PhD; M. van Weel, MD; Roland Wick, PhD; Melanie Weiss, MD; H. Grant Prentice, MB, FRCP, FRCPath; for the Late Effects Working Party of the European Cooperative Group for Blood and Marrow Transplantation and the European Late Effect Project Group
Grant Support: In part by the European Late Effect Project Group and Council Economic Community contract FI3P-CT920064f—epidemiologic studies and tables.
Requests for Reprints: H.J. Kolb, MD, PhD, Hematopoietic Cell Transplantation, Medical Clinic III, University of Munich, Marchioninistrasse 15, 81377 München, Germany.
Current Author Addresses: Drs. Kolb and Duell: Hematopoietic Cell Transplantation, Medical Clinic III, GSF-National Research Center for Environment and Health, Marchioninistrasse 15, 81377 München, Germany.
Drs. Nekolla and Wick: Radiobiological Institute, GSF-National Research Center for Environment and Health, Ingolstädter Landstrasse 1, München-Neuherberg, Germany.
Dr. Socié: Hôpital St. Louis, Centre Hayem, 1 avenue Claude Vellefaux, 750475 Paris, France.
Dr. Van Lint: Ospedale San Martino, Centro Trapianti Midollo Osseo, Divisione Ematologia, Viale Benedetto XV, 1-16132 Genova, Italy.
Dr. Tichelli: Kantonsspital Basel, Department of Haematology, Petersgraben 4, CH 4041 Basel, Switzerland.
Dr. Apperley: Hammersmith Hospital, Royal Postgraduate School of Medicine, DuCane Road 4, London, United Kingdom.
Dr. Ljungman: Department of Medicine, Huddinge Hospital, Huddinge, Sweden.
Dr. Jacobsen: BMT Unit Blegdamsvej, 9 Rigshospitalet, Copenhagen, Denmark.
Dr. van Weel: Department of Pediatrics, University Hospital, Leiden, Netherlands.
Dr. Weiss: Institut für Arbeitsmedizin, Universität Ulm, Ulm, Germany.
Dr. Prentice: Royal Free Hospital London, Hampstead, London, United Kingdom.
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.
To determine the risk and define potential risk factors for new malignant conditions in long-term survivors after marrow transplantation.
Retrospective multicenter study.
Study of the Late Effects Working Party with 45 transplantation centers cooperating in the European Cooperative Group for Blood and Marrow Transplantation.
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.
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.
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.
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.
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Kolb HJ, Socié G, Duell T, Van Lint MT, Tichelli A, Apperley JF, et al. Malignant Neoplasms in Long-Term Survivors of Bone Marrow Transplantation. Ann Intern Med. 1999;131:738–744. doi: 10.7326/0003-4819-131-10-199911160-00004
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Published: Ann Intern Med. 1999;131(10):738-744.
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