Correspondence

Solid Cancers after Bone Marrow Transplantation

N Engl J Med 1997; 337:345-346July 31, 1997

Article

To the Editor:

Curtis et al. (March 27 issue)1 conclude that patients undergoing bone marrow transplantation have an increased risk of new solid cancers later in life. The authors calculated the observed numbers of solid cancers on the basis of data from 19,229 patients who had received allogeneic or syngeneic transplants between 1964 and 1992 at 235 centers, with the expected numbers of solid cancers calculated on the basis of data obtained from selected registries in the United States, England and Wales, Europe, and Asia. The authors then calculated the ratios of observed to expected cases and the corresponding 95 percent confidence intervals, which suggested an elevated risk of new solid cancers among patients who had undergone bone marrow transplantation.

This comparison may be invalid, because the patients with cancers (such as acute lymphoblastic leukemia or acute nonlymphocytic leukemia) who underwent transplantation may have had a much higher risk of new solid cancers than the general population. Therefore, the correct comparison group for calculating the expected numbers of new cancers should be patients who had cancers (such as acute lymphoblastic leukemia or acute nonlymphocytic leukemia) and did not undergo bone marrow transplantation.

Shenghan Lai, M.D., M.P.H.
J. Bryan Page, Ph.D.
Hong Lai, M.P.H.
University of Miami School of Medicine, Miami, FL 33101

1 References

1. 1

   Curtis RE, Rowlings PA, Deeg HJ, et al. Solid cancers after bone marrow transplantation. N Engl J Med 1997;336:897-904
   Full Text | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: Lai et al. question the validity of comparing the incidence of solid cancers after bone marrow transplantation with the risk of cancer in the general population. Since most of the transplant recipients in our study had an initial diagnosis of leukemia, Lai et al. speculate that such patients may have a higher risk of new solid cancers than the general population. Regrettably, little information is available on the risk of solid tumors after treatment for leukemia in the nontransplantation setting.1-3 Data are particularly sparse for patients with acute or chronic myelogenous leukemia, the types that predominate among transplant recipients. These patients had a poor prognosis before the transplantation era, with very limited follow-up time in which to observe new cancers. Thus, we were not able to use as a comparison group patients with leukemia who had not undergone transplantation, as Lai and colleagues as well as others suggest.

We agree that factors associated with the primary disease may influence the risk of solid tumors among transplant recipients, especially the effects of treatment for the initial cancer before transplantation. For example, we reported that cranial irradiation before transplantation in patients with acute leukemia is likely to be related to the increased risk of solid cancers observed in our cohort, although the effect appears to be limited to cancers at certain anatomical sites (the brain and thyroid) and to younger age groups (<10 years).

Non–transplant-associated factors other than treatment for the primary disease, including shared genetic and environmental risk factors, could also influence the subsequent risk of cancer. However, if the results of previous studies of multiple primary cancers are generalizable, such factors are unlikely to result in the 5-to-10-fold elevation in risk after bone marrow transplantation. It should also be emphasized that a number of our major findings, including the dose–response relation between total-body irradiation and the risk of cancer, were based on comparisons within the transplantation cohort and did not rely on the use of the general population as a comparison group.

Although there are probably multiple causes of the increased risk of solid cancers after transplantation, the conclusions of our report remain valid: survivors of allogeneic bone marrow transplantation have a substantially increased risk of new solid cancers, and lifelong surveillance is essential.

Rochelle E. Curtis, M.A.
National Cancer Institute, Bethesda, MD 20852

Philip A. Rowlings, M.B., B.S.
Medical College of Wisconsin, Milwaukee, WI 53226

H. Joachim Deeg, M.D.
Fred Hutchinson Cancer Research Center, Seattle, WA 98104

3 References

1. 1

   Neglia JP, Meadows AT, Robison LL, et al. Second neoplasms after acute lymphoblastic leukemia in childhood. N Engl J Med 1991;325:1330-1336
   Full Text | Web of Science | Medline

2. 2

   Hawkins MM, Draper GJ, Kingston JE. Incidence of second primary tumours among childhood cancer survivors. Br J Cancer 1987;56:339-347
   CrossRef | Web of Science | Medline

3. 3

   Olsen JH, Garwicz S, Hertz H, et al. Second malignant neoplasms after cancer in childhood or adolescence. BMJ 1993;307:1030-1036
   CrossRef | Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   Dipak Ghelani, Rima Saliba, Marcos de Lima. (2005) Secondary malignancies after hematopoietic stem cell transplantation. Critical Reviews in Oncology/Hematology 56:1, 115-126
   CrossRef