To investigate the effect of different treatments for Hodgkin's disease on the risk of leukemia, we used an international collaborative group of cancer registries and hospitals to perform a case-control study of 163 cases of leukemia following treatment for Hodgkin's disease. For each case patient with leukemia, three matched controls were chosen who had been treated for Hodgkin's disease but in whom leukemia did not develop. The use of chemotherapy alone to treat Hodgkin's disease was associated with a relative risk of leukemia of 9.0 (95 percent confidence interval, 4.1 to 20) as compared with the use of radiotherapy alone. Patients treated with both had a relative risk of 7.7 (95 percent confidence interval, 3.9 to 15). After treatment with more than six cycles of combinations including procarbazine and mechlorethamine, the risk of leukemia was 14-fold higher than after radiotherapy alone. The use of radiotherapy in combination with chemotherapy did not increase the risk of leukemia above that produced by the use of chemotherapy alone, but there was a dose-related increase in the risk of leukemia in patients who received radiotherapy alone. The peak in the risk of leukemia came about five years after chemotherapy began, and a large excess persisted for at least eight years after it ended. After adjusting for drug regimen, we found that patients who had undergone splenectomy had at least double the risk of leukemia of patients who had not, and an advanced stage of Hodgkin's disease carried a somewhat higher risk of leukemia than Stage I disease. We conclude that chemotherapy for Hodgkin's disease greatly increases the risk of leukemia and that this increased risk appears to be dose-related and unaffected by concomitant radiotherapy. In addition, the risk is greater for patients with more advanced stages of Hodgkin's disease and for those who undergo splenectomy.
Source Information
International Agency for Research on Cancer, Lyon, France.
This article has been cited by other articles:
Little, M. P.
(2008). Leukaemia following childhood radiation exposure in the Japanese atomic bomb survivors and in medically exposed groups. Radiat Prot Dosimetry
132: 156-165
[Abstract][Full Text]
Ng, A. K.
(2008). Second Cancers after Hodgkin's Lymphoma: Long-term Risks. Am Soc Clin Oncol Ed Book
2008: 418-422
[Abstract][Full Text]
Barlogie, B., Tricot, G., Haessler, J., van Rhee, F., Cottler-Fox, M., Anaissie, E., Waldron, J., Pineda-Roman, M., Thertulien, R., Zangari, M., Hollmig, K., Mohiuddin, A., Alsayed, Y., Hoering, A., Crowley, J., Sawyer, J.
(2008). Cytogenetically defined myelodysplasia after melphalan-based autotransplantation for multiple myeloma linked to poor hematopoietic stem-cell mobilization: the Arkansas experience in more than 3000 patients treated since 1989. Blood
111: 94-100
[Abstract][Full Text]
Tebbi, C. K., London, W. B., Friedman, D., Villaluna, D., De Alarcon, P. A., Constine, L. S., Mendenhall, N. P., Sposto, R., Chauvenet, A., Schwartz, C. L.
(2007). Dexrazoxane-Associated Risk for Acute Myeloid Leukemia/Myelodysplastic Syndrome and Other Secondary Malignancies in Pediatric Hodgkin's Disease. JCO
25: 493-500
[Abstract][Full Text]
Franklin, J, Pluetschow, A, Paus, M, Specht, L, Anselmo, A-P, Aviles, A, Biti, G, Bogatyreva, T, Bonadonna, G, Brillant, C, Cavalieri, E, Diehl, V, Eghbali, H, Ferme, C, Henry-Amar, M, Hoppe, R, Howard, S, Meyer, R, Niedzwiecki, D, Pavlovsky, S, Radford, J, Raemaekers, J, Ryder, D, Schiller, P, Shakhtarina, S, Valagussa, P, Wilimas, J, Yahalom, J
(2006). Second malignancy risk associated with treatment of Hodgkin's lymphoma: meta-analysis of the randomised trials. Ann Oncol
17: 1749-1760
[Abstract][Full Text]
Travis, L. B.
(2006). The Epidemiology of Second Primary Cancers. Cancer Epidemiol. Biomarkers Prev.
15: 2020-2026
[Abstract][Full Text]
Fenske, T. S., McMahon, C., Edwin, D., Jarvis, J. C., Cheverud, J. M., Minn, M., Mathews, V., Bogue, M. A., Province, M. A., McLeod, H. L., Graubert, T. A.
(2006). Identification of candidate alkylator-induced cancer susceptibility genes by whole genome scanning in mice.. Cancer Res.
66: 5029-5038
[Abstract][Full Text]
Mudie, N. Y., Swerdlow, A. J., Higgins, C. D., Smith, P., Qiao, Z., Hancock, B. W., Hoskin, P. J., Linch, D. C.
(2006). Risk of Second Malignancy After Non-Hodgkin's Lymphoma: A British Cohort Study. JCO
24: 1568-1574
[Abstract][Full Text]
Schonfeld, S. J., Gilbert, E. S., Dores, G. M., Lynch, C. F., Hodgson, D. C., Hall, P., Storm, H., Andersen, A., Pukkala, E., Holowaty, E., Kaijser, M., Andersson, M., Joensuu, H., Fossa, S. D., Allan, J. M., Travis, L. B.
(2006). Acute Myeloid Leukemia Following Hodgkin Lymphoma: A Population-Based Study of 35 511 Patients. JNCI J Natl Cancer Inst
98: 215-218
[Abstract][Full Text]
Forrest, D. L., Hogge, D. E., Nevill, T. J., Nantel, S. H., Barnett, M. J., Shepherd, J. D., Sutherland, H. J., Toze, C. L., Smith, C. A., Lavoie, J. C., Song, K. W., Voss, N. J., Gascoyne, R. D., Connors, J. M.
(2005). High-Dose Therapy and Autologous Hematopoietic Stem-Cell Transplantation Does Not Increase the Risk of Second Neoplasms for Patients With Hodgkin's Lymphoma: A Comparison of Conventional Therapy Alone Versus Conventional Therapy Followed by Autologous Hematopoietic Stem-Cell Transplantation. JCO
23: 7994-8002
[Abstract][Full Text]
Bennett, J. M., Kaminski, M. S., Leonard, J. P., Vose, J. M., Zelenetz, A. D., Knox, S. J., Horning, S., Press, O. W., Radford, J. A., Kroll, S. M., Capizzi, R. L.
(2005). Assessment of treatment-related myelodysplastic syndromes and acute myeloid leukemia in patients with non-Hodgkin lymphoma treated with tositumomab and iodine I131 tositumomab. Blood
105: 4576-4582
[Abstract][Full Text]
Bhatia, S., Robison, L. L., Francisco, L., Carter, A., Liu, Y., Grant, M., Baker, K. S., Fung, H., Gurney, J. G., McGlave, P. B., Nademanee, A., Ramsay, N. K. C., Stein, A., Weisdorf, D. J., Forman, S. J.
(2005). Late mortality in survivors of autologous hematopoietic-cell transplantation: report from the Bone Marrow Transplant Survivor Study. Blood
105: 4215-4222
[Abstract][Full Text]
Pagano, L., Pulsoni, A., Vignetti, M., Tosti, M. E., Falcucci, P., Fazi, P., Fianchi, L., Levis, A., Bosi, A., Angelucci, E., Bregni, M., Gabbas, A., Peta, A., Coser, P., Ricciuti, F., Morselli, M., Caira, M., Foa, R., Amadori, S., Mandelli, F., Leone, G., On behalf of GIMEMA,
(2005). Secondary acute myeloid leukaemia: results of conventional treatments. Experience of GIMEMA trials. Ann Oncol
16: 228-233
[Abstract][Full Text]
Ng, A. K., Li, S., Neuberg, D., Silver, B., Stevenson, M. A., Fisher, D. C., Mauch, P. M.
(2004). Comparison of MOPP versus ABVD as salvage therapy in patients who relapse after radiation therapy alone for Hodgkin's disease. Ann Oncol
15: 270-275
[Abstract][Full Text]
Souliotis, V. L., Dimopoulos, M. A., Sfikakis, P. P.
(2003). Gene-specific Formation and Repair of DNA Monoadducts and Interstrand Cross-links after Therapeutic Exposure to Nitrogen Mustards. Clin. Cancer Res.
9: 4465-4474
[Abstract][Full Text]
Aleman, B. M.P., van den Belt-Dusebout, A. W., Klokman, W. J., van't Veer, M. B., Bartelink, H., van Leeuwen, F. E.
(2003). Long-Term Cause-Specific Mortality of Patients Treated for Hodgkin's Disease. JCO
21: 3431-3439
[Abstract][Full Text]
Aleman, B. M.P., Raemaekers, J. M.M., Tirelli, U., Bortolus, R., van 't Veer, M. B., Lybeert, M. L.M., Keuning, J. J., Carde, P., Girinsky, T., van der Maazen, R. W.M., Tomsic, R., Vovk, M., van Hoof, A., Demeestere, G., Lugtenburg, P. J., Thomas, J., Schroyens, W., De Boeck, K., Baars, J. W., Kluin-Nelemans, J. C., Carrie, C., Aoudjhane, M., Bron, D., Eghbali, H., Smit, W. G.J.M., Meerwaldt, J. H., Hagenbeek, A., Pinna, A., Henry-Amar, M., the European Organization for Research and Treatme,
(2003). Involved-Field Radiotherapy for Advanced Hodgkin's Lymphoma. NEJM
348: 2396-2406
[Abstract][Full Text]
Arriagada, R., Gutierrez, J.
(2003). Anthracyclines: is more, better and/or more dangerous?. Ann Oncol
14: 663-665
[Full Text]
Le Deley, M.-C., Leblanc, T., Shamsaldin, A., Raquin, M.-A., Lacour, B., Sommelet, D., Chompret, A., Cayuela, J.-M., Bayle, C., Bernheim, A., de Vathaire, F., Vassal, G., Hill, C.
(2003). Risk of Secondary Leukemia After a Solid Tumor in Childhood According to the Dose of Epipodophyllotoxins and Anthracyclines: A Case-Control Study by the Societe Francaise d'Oncologie Pediatrique. JCO
21: 1074-1081
[Abstract][Full Text]
Metayer, C., Curtis, R. E., Vose, J., Sobocinski, K. A., Horowitz, M. M., Bhatia, S., Fay, J. W., Freytes, C. O., Goldstein, S. C., Herzig, R. H., Keating, A., Miller, C. B., Nevill, T. J., Pecora, A. L., Rizzo, J. D., Williams, S. F., Li, C.-Y., Travis, L. B., Weisdorf, D. J.
(2003). Myelodysplastic syndrome and acute myeloid leukemia after autotransplantation for lymphoma: a multicenter case-control study. Blood
101: 2015-2023
[Abstract][Full Text]
Duggan, D. B., Petroni, G. R., Johnson, J. L., Glick, J. H., Fisher, R. I., Connors, J. M., Canellos, G. P., Peterson, B. A.
(2003). Randomized Comparison of ABVD and MOPP/ABV Hybrid for the Treatment of Advanced Hodgkin's Disease: Report of an Intergroup Trial. JCO
21: 607-614
[Abstract][Full Text]
Radman, I., Basic, N., Labar, B., Kovacevic, J., Aurer, I., Bogdanic, V., Zupancic-Salek, S., Nemet, D., Jakic-Razumovic, J., Mrsic, M., Santek, F., Grgic-Markulin, L., Boban, D.
(2002). Long-term results of conventional-dose salvage chemotherapy in patients with refractory and relapsed Hodgkin's disease (Croatian experience). Ann Oncol
13: 1650-1655
[Abstract][Full Text]
Ng, A. K., Bernardo, M. V. P., Weller, E., Backstrand, K., Silver, B., Marcus, K. C., Tarbell, N. J., Stevenson, M. A., Friedberg, J. W., Mauch, P. M.
(2002). Second malignancy after Hodgkin disease treated with radiation therapy with or without chemotherapy: long-term risks and risk factors. Blood
100: 1989-1996
[Abstract][Full Text]
Buschfort-Papewalis, C., Moritz, T., Liedert, B., Thomale, J.
(2002). Down-regulation of DNA repair in human CD34+ progenitor cells corresponds to increased drug sensitivity and apoptotic response. Blood
100: 845-853
[Abstract][Full Text]
Allan, J. M., Wild, C. P., Rollinson, S., Willett, E. V., Moorman, A. V., Dovey, G. J., Roddam, P. L., Roman, E., Cartwright, R. A., Morgan, G. J.
(2001). Polymorphism in glutathione S-transferase P1 is associated with susceptibility to chemotherapy-induced leukemia. Proc. Natl. Acad. Sci. USA
10.1073/pnas.191211198v1
[Abstract][Full Text]
Lillington, D. M., Micallef, I. N.M., Carpenter, E., Neat, M. J., Amess, J. A.L., Matthews, J., Foot, N. J., Young, B. D., Lister, T. A., Rohatiner, A. Z.S.
(2001). Detection of Chromosome Abnormalities Pre-High-Dose Treatment in Patients Developing Therapy-Related Myelodysplasia and Secondary Acute Myelogenous Leukemia After Treatment for Non-Hodgkin's Lymphoma. JCO
19: 2472-2481
[Abstract][Full Text]
Rueffer, U., Josting, A., Franklin, J., May, M., Sieber, M., Breuer, K., Engert, A., Diehl, V.
(2001). Non-Hodgkin's Lymphoma After Primary Hodgkin's Disease in the German Hodgkin's Lymphoma Study Group: Incidence, Treatment, and Prognosis. JCO
19: 2026-2032
[Abstract][Full Text]
Travis, L. B., Andersson, M., Gospodarowicz, M., van Leeuwen, F. E., Bergfeldt, K., Lynch, C. F., Curtis, R. E., Kohler, B. A., Wiklund, T., Storm, H., Holowaty, E., Hall, P., Pukkala, E., Sleijfer, D. T., Clarke, E. A., Boice, J. D. Jr., Stovall, M., Gilbert, E.
(2000). Treatment-Associated Leukemia Following Testicular Cancer. JNCI J Natl Cancer Inst
92: 1165-1171
[Abstract][Full Text]
Green, D. M., Hyland, A., Barcos, M. P., Reynolds, J. A., Lee, R. J., Hall, B. C., Zevon, M. A.
(2000). Second Malignant Neoplasms After Treatment for Hodgkin’s Disease in Childhood or Adolescence. JCO
18: 1492-1499
[Abstract][Full Text]
Krishnan, A., Bhatia, S., Slovak, M. L., Arber, D. A., Niland, J. C., Nademanee, A., Fung, H., Bhatia, R., Kashyap, A., Molina, A., O'Donnell, M. R., Parker, P. A., Sniecinski, I., Snyder, D. S., Spielberger, R., Stein, A., Forman, S. J.
(2000). Predictors of therapy-related leukemia and myelodysplasia following autologous transplantation for lymphoma: an assessment of risk factors. Blood
95: 1588-1593
[Abstract][Full Text]
Swerdlow, A. J., Barber, J. A., Hudson, G. V., Cunningham, D., Gupta, R. K., Hancock, B. W., Horwich, A., Lister, T. A., Linch, D. C.
(2000). Risk of Second Malignancy After Hodgkin’s Disease in a Collaborative British Cohort: The Relation to Age at Treatment. JCO
18: 498-498
[Abstract][Full Text]
Linch, D. C., Gosden, R. G., Tulandi, T., Tan, S.-L., Hancock, S. L.
(2000). Hodgkin's Lymphoma: Choice of Therapy and Late Complications. ASH Education Book
2000: 205-221
[Abstract][Full Text]
Friedberg, J. W., Neuberg, D., Stone, R. M., Alyea, E., Jallow, H., LaCasce, A., Mauch, P. M., Gribben, J. G., Ritz, J., Nadler, L. M., Soiffer, R. J., Freedman, A. S.
(1999). Outcome in Patients With Myelodysplastic Syndrome After Autologous Bone Marrow Transplantation for Non-Hodgkin's Lymphoma. JCO
17: 3128-3135
[Abstract][Full Text]
Travis, L. B., Holowaty, E. J., Bergfeldt, K., Lynch, C. F., Kohler, B. A., Wiklund, T., Curtis, R. E., Hall, P., Andersson, M., Pukkala, E., Sturgeon, J., Stovall, M., Storm, H., Clarke, E. A., Boice, J. D., Gospodarowicz, M.
(1999). Risk of Leukemia after Platinum-Based Chemotherapy for Ovarian Cancer. NEJM
340: 351-357
[Abstract][Full Text]
Smith, M. A., Rubinstein, L., Anderson, J. R., Arthur, D., Catalano, P. J., Freidlin, B., Heyn, R., Khayat, A., Krailo, M., Land, V. J., Miser, J., Shuster, J., Vena, D.
(1999). Secondary Leukemia or Myelodysplastic Syndrome After Treatment With Epipodophyllotoxins. JCO
17: 569-569
[Abstract][Full Text]
Aisenberg, A. C.
(1999). Problems in Hodgkin's Disease Management. Blood
93: 761-779
[Full Text]
Barosi, G., Ambrosetti, A., Centra, A., Falcone, A., Finelli, C., Foa, P., Grossi, A., Guarnone, R., Rupoli, S., Luciano, L., Petti, M. C., Pogliani, E., Russo, D., Ruggeri, M., Quaglini, S., Italian Cooperative Study Group on Myelofibrosis W, t.
(1998). Splenectomy and Risk of Blast Transformation in Myelofibrosis With Myeloid Metaplasia. Blood
91: 3630-3636
[Abstract][Full Text]
Tramo, M. J., Loftus, W. C., Stukel, T. A., Green, R. L., Weaver, J. B., Gazzaniga, M. S.
(1998). Brain size, head size, and intelligence quotient in monozygotic twins. Neurology
50: 1246-1252
[Abstract][Full Text]
Fernandez, G., Effenberger, O., Vinz, B., Steinlein, O., Elger, C. E., Dohring, W., Heinze, H. J.
(1998). Hippocampal malformation as a cause of familial febrile convulsions and subsequent hippocampal sclerosis. Neurology
50: 909-917
[Abstract][Full Text]
PELLEGRINI, V. D. JR., GREGORITCH, S. J.
(1996). Preoperative Irradiation for Prevention of Heterotopic Ossification following Total Hip Arthroplasty. JBJS
78: 870-81
[Abstract][Full Text]
Bhatia, S., Robison, L. L., Oberlin, O., Greenberg, M., Bunin, G., Fossati-Bellani, F., Meadows, A. T.
(1996). Breast Cancer and Other Second Neoplasms after Childhood Hodgkin's Disease. NEJM
334: 745-751
[Abstract][Full Text]
Multani, P. S., Grossbard, M. L.
(1996). Staging Laparotomy in the Management of Hodgkin's Disease: Is it Still Necessary?. The Oncologist
1: 41-55
[Abstract][Full Text]
Socie, G., Henry-Amar, M., Bacigalupo, A., Hows, J., Tichelli, A., Ljungman, P., McCann, S. R., Frickhofen, N., Van't Veer-Korthof, E., Gluckman, E., The European Bone Marrow Transplantation-Severe Ap,
(1993). Malignant Tumors Occurring after Treatment of Aplastic Anemia. NEJM
329: 1152-1157
[Abstract][Full Text]
Figueroa, M., Gehlsen, J., Hammond, D., Ondreyco, S., Piro, L., Pomeroy, T., Williams, F., McMillan, R.
(1993). Combination Chemotherapy in Refractory Immune Thrombocytopenic Purpura. NEJM
328: 1226-1229
[Abstract][Full Text]
(1990). LEUKEMIA AFTER TREATMENT FOR HODGKIN'S DISEASE. JWatch General
1990: 2-2
[Full Text]
Allan, J. M., Wild, C. P., Rollinson, S., Willett, E. V., Moorman, A. V., Dovey, G. J., Roddam, P. L., Roman, E., Cartwright, R. A., Morgan, G. J.
(2001). Polymorphism in glutathione S-transferase P1 is associated with susceptibility to chemotherapy-induced leukemia. Proc. Natl. Acad. Sci. USA
98: 11592-11597
[Abstract][Full Text]
Previous
