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16 November 1999, Vol 131, No. 10>
Articles | 16 November 1999

Malignant Neoplasms in Long-Term Survivors of Bone Marrow Transplantation

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, Late Effects Working Party of the European Cooperative Group for Blood and Marrow Transplantation and the European Late Effect Project Group
[+] Article and Author Information

From Hematopoietic Cell Transplantation Unit, Medical Department III, LM University, and GSF-National Research Center for Environment and Health, Munich, Germany.


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.


Ann Intern Med. 1999;131(10):738-744. doi:10.7326/0003-4819-131-10-199911160-00004
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Bone marrow transplantation offers a chance for cure to patients with leukemia, lymphoma, and severe aplastic anemia (1 - 3). However, long-term survival may be impaired by the development of secondary neoplasms (4). Secondary malignant diseases are known complications of the radiation and chemotherapy used to treat primary cancers (5 - 7). An increased risk for malignant neoplasms has also been reported in patients who receive organ transplants (8 - 9) and those treated with immunosuppression for aplastic anemia (10). Patients who receive marrow transplants are at increased risk for malignant neoplasms because of several risk factors: ionizing radiation and chemotherapy used for pretransplantation conditioning and treatment of the primary malignant disease, immune deficiency due to delayed and incomplete recovery of the immune system, immune stimulation and immunosuppression by the graft-versus-host reaction, and immunosuppressive therapy for graft-versus-host disease. Most reports on malignant neoplasm after marrow transplantation have included patients early after transplantation and have had short follow-up (1,4,11 - 15). A recent multicenter study of more than 19 000 patients (16) included patients early after transplantation and evaluated solid cancers only.

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Figures

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Figure 1.
Cumulative probability of developing a malignant neoplasm as a function of time after bone marrow transplantation.n

Patients ( = 1036) underwent transplantation before 1986 and had survived at least 5 years; data were collected until March 1996. The gray shaded area shows the number of patients under observation as a function of time after transplantation (person-years at risk). The step function with the hatched range of SEs represents the observed cumulative tumor incidence: that is, the probability of developing malignant disease up to the specified time. The dotted line shows values according to the age-specific incidence rates from the Saarland Cancer Registry and the Danish Cancer Registry. The vertical dashed line shows the median observation time after transplantation.

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Figure 2.
Cumulative number of malignant neoplasms after bone marrow transplantation as a function of age.

The gray shaded area shows the age distribution during the observation period, indicating the person-years at risk at a specific age. The step function with the hatched range of SEs represents the observed cumulative tumor incidence at a specific age. The dotted line gives the age-specific incidence rates from the Saarland Cancer Registry and the Danish Cancer Registry.

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Figure 3.
Standardized incidence ratios of malignant neoplasms after bone marrow transplantation.circles

The standardized incidence ratios of the observed versus the expected number of cases ( ) and their one-sided 95% CIs are given for different types of cancer. The expected number of cases is computed from the age- and sex-specific person-years at risk and the age-specific incidence rates from the Cancer Registry of Saarland and the Danish Cancer Registry.

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Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s “Cited By” API will populate this tab (http://www.crossref.org/citedby.html).
Compression-Only CPR: Pushing the Science Forward
Cone
AAM 2010;304:1493-1495.
All you need to read in the other general jounals
BMJ 2010;341:c5893-c1494.

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Summary for Patients

New Cancers in People Who Have Had Bone Marrow Transplants

The summary below is from the full report titled “Malignant Neoplasms in Long-Term Survivors of Bone Marrow Transplantation.” It is in the 16 November 1999 issue of Annals of Internal Medicine (volume 131, pages 738-734). The authors are H.J. Kolb, G. Socié, T. Duell, M.T. Van Lint, A. Tichelli, J.F. Apperley, E. Nekolla, P. Ljungman, N. Jacobsen, M. van Weel, R. Wick, M. Weiss, and H.G. Prentice, for the Late Effects Working Party of the European Cooperative Group for Blood and Marrow Transplantation and the European Late Effect Project Group.

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