Abstract
To investigate the cumulative incidence of second malignancy and the competing risk of death due to any other cause in patients who were treated for childhood acute myeloid leukemia (AML), we analyzed the outcomes in a cohort of 501 patients who were treated at St Jude Children's Research Hospital between 1970 and 1996. Five patients developed a second cancer (two carcinomas of the parotid gland, one non-Hodgkin's lymphoma, one supratentorial primitive neuroectodermal tumor, one acute lymphoblastic leukemia) as compared with 0.47 expected in the general population (standardized incidence ratio, 10.64; 95% confidence interval, 3.28 to 22.34). A third neoplasm (meningioma) developed in one patient. At 15 years after the diagnosis of AML, the estimated cumulative incidence of second malignancy was 1.34% ± 0.61%, whereas the cumulative incidence of death due to any other cause was 72.96% ± 2.14%. We concluded that although a more than 10-fold increased risk of development of cancer was found in survivors of childhood AML as compared to the general population, the risk of this late complication is small when compared to the much larger risk of death because of the primary leukemia or the early complications of its treatment. Future studies should focus on improving treatments for primary AML while preventing second malignancies.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Pui CH . Childhood leukemias N Engl J Med 1995 332: 1618–1630
Leung W, Hudson MM, Strickland DK, Phipps S, Srivastava DK, Ribeiro RC, Rubnitz JE, Sandlund JT, Kun LE, Bowman LC, Razzouk BI, Mathew P, Evans WE, Pui CH . Late effects of treatment in survivors of childhood acute myeloid leukemia J Clin Oncol 2000 18: 3273–3279
Fleming I, Simone J, Jackson R, Johnson W, Walters T, Mason C . Splenectomy and chemotherapy in acute myelocytic leukemia of childhood Cancer 1974 33: 427–434
Dahl GV, Simone JV, Hustu HO, Mason C . Preventive central nervous system irradiation in children with acute nonlymphocytic leukemia Cancer 1978 42: 2187–2192
Dahl GV, Kalwinsky DK, Murphy S, Look AT, Amadori S, Kumar M, Novak R, George SL, Mason C, Mauer AM, Simone JV . Cytokinetically based induction chemotherapy and splenectomy for childhood acute nonlymphocytic leukemia Blood 1982 60: 856–863
Dahl GV, Kalwinsky DK, Mirro J Jr, Look AT, Pui CH, Murphy SB, Mason C, Ruggiero M, Schell M, Johnson FL . Allogeneic bone marrow transplantation in a program of intensive sequential chemotherapy for children and young adults with acute nonlymphocytic leukemia in first remission J Clin Oncol 1990 8: 295–303
Kalwinsky D, Mirro J Jr, Schell M, Behm F, Mason C, Dahl GV . Early intensification of chemotherapy for childhood acute nonlymphoblastic leukemia: improved remission induction with a five-drug regimen including etoposide J Clin Oncol 1988 6: 1134–1143
Arnaout MK, Radomski KM, Srivastava DK, Tong X, Belt JR, Raimondi SC, Behm FG, Santanta VM, Crom WR, Mirro J, Ribeiro RC . Treatment of childhood acute myelogenous leukemia with an intensive regimen (AML-87) that individualizes etoposide and cytarabine dosages: short- and long-term effects Leukemia 2000 (in press
Hurwitz CA, Krance R, Schell MJ, Santana VM, Brenner MK, Ribeirio R, Roberts WM, Mahmoud H, Belt J, Crom W . Current strategies for treatment of acute myeloid leukemia at St Jude Children's Research Hospital Leukemia 1992 6: (suppl 2) 39–43
Beaty O III, Hudson MM, Greenwald C, Luo X, Fang L, Wilimas JA, Thompson EI, Kun LE, Pratt CB . Subsequent malignancies in children and adolescents after treatment for Hodgkin's disease J Clin Oncol 1995 13: 603–609
Leung W, Hudson M, Zhu Y, Rivera GK, Ribeiro RC, Sandlund JT, Bowman LC, Evans WE, Kun L, Pui CH . Late effects in survivors of infant leukemia Leukemia 2000 14: 1185–1190
Pui CH, Raimondi SC, Head DR, Schell MJ, Rivera GK, Mirro J Jr, Crist WM, Behm FG . Characterization of childhood acute leukemia with multiple myeloid and lymphoid markers at diagnosis and at relapse Blood 1991 78: 1327–1337
Gray RJ . A class of K-sample tests for comparing the cumulative incidence of a competing risk Ann Stat 1988 16: 1141–1154
Ries LAG, Eisner MP, Kosary CL (eds) . SEER Cancer Statistics Review, 1973–1997 National Cancer Institute: Bethesda, MD 2000
Vandenbroucke JP . A shortcut method for calculating the 95 per cent confidence interval of the standardized mortality ratio Am J Epidemiol 1982 115: 303–304
Mirro J Jr, Kalwinsky DK, Grier HE, Santana VM, Mason C, Murphy SB, Dahl GV . Effective reinduction therapy for childhood acute nonlymphoid leukemia using simultaneous continuous infusions of teniposide and amsacrine Cancer Chemother Pharmacol 1989 24: 123–127
Li FP, Cassady JR, Jaffe N . Risk of second tumors in survivors of childhood cancer Cancer 1975 35: 1230–1235
Mike V, Meadows AT, D'Angio GJ . Incidence of second malignant neoplasms in children: results of an international study Lancet 1982 2: 1326–1331
Meadows AT, Baum E, Fossati-Bellani F, Green D, Jenkin RD, Marsden B, Nesbit M, Newton W, Oberlin O, Sallan SG . Second malignant neoplasms in children: an update from the Late Effects Study Group J Clin Oncol 1985 3: 532–538
Olsen JH . Risk of second cancer after cancer in childhood Cancer 1986 57: 2250–2254
de Vathaire F, Schweisguth O, Rodary C, Francois P, Sarrazin D, Oberlin O, Hill C, Raquin MA, Dutreix A, Flamant R . Long-term risk of second malignant neoplasm after a cancer in childhood Br J Cancer 1989 59: 448–452
Blatt J, Olshan A, Gula MJ, Dickman PS, Zaranek B . Second malignancies in very long-term survivors of childhood cancer Am J Med 1992 93: 57–60
Olsen JH, Garwicz S, Hertz H, Jonmundsson G, Langmark F, Lanning M, Lie SO, Moe PJ, Moller T, Sankila R . Second malignant neoplasms after cancer in childhood or adolescence. Nordic Society of Paediatric Haematology and Oncology Association of the Nordic Cancer Registries Br Med J 1993 307: 1030–1036
de Vathaire F, Hawkins M, Campbell S, Oberlin O, Raquin MA, Schlienger, Shamsaldin A, Diallo I, Bell J, Grimaud E, Hardiman C, Lagrange JL, Daly-Schveitzer N, Panis X, Zucker JM, Sancho-Garnier H, Eschwege F, Chavaudra J, Lemerle J . Second malignant neoplasms after a first cancer in childhood: temporal pattern of risk according to type of treatment Br J Cancer 1999 79: 1884–1893
Hawkins MM, Draper GJ, Kingston JE . Incidence of second primary tumours among childhood cancer survivors Br J Cancer 1987 56: 339–347
Terracini B, Pastore G, Zurlo MG, Masera G, Fossati-Bellani F, Castello M, Tamaro P, Massolo F, Rosati D, Biddau PF . Late deaths and second primary malignancies among long-term survivors of childhood cancer: an Italian multicentre study Eur J Cancer Clin Oncol 1987 23: 499–504
Rosso P, Terracini B, Fears TR, Jankovic M, Fossati Bellani F, Arrighini A, Carli M, Cordero di Montezemolo L, Garre ML, Guazzelli C . Second malignant tumors after elective end of therapy for a first cancer in childhood: a multicenter study in Italy Int J Cancer 1994 59: 451–456
Green DM, Zevon MA, Reese PA, Lowrie GS, Gaeta JF, Pearce JI, Michalek AM, Stephens EA . Second malignant tumors following treatment during childhood and adolescence for cancer Med Pediatr Oncol 1994 22: 1–10
Neglia JP, Meadows AT, Robison LL, Kim TH, Newton WA, Ruymann FB, Sather HN, Hammond GD . Second neoplasms after acute lymphoblastic leukemia in childhood N Engl J Med 1991 325: 1330–1336
Nygaard R, Garwicz S, Haldorsen T, Hertz H, Jonmundsson GK, Lanning M, Moe PJ . Second malignant neoplasms in patients treated for childhood leukemia. A population-based cohort study from the Nordic countries. The Nordic Society of Pediatric Oncology and Hematology (NOPHO) Acta Paediatr Scand 1991 80: 1220–1228
Kimball Dalton VM, Gelber RD, Li F, Donnelly MJ, Tarbell NJ, Sallan SE . Second malignancies in patients treated for childhood acute lymphoblastic leukemia J Clin Oncol 1998 16: 2848–2853
Kubota M, Akiyama Y, Koishi S, Sawada M, Usami I, Lin YW, Watanabe K, Takimoto T . Second malignancy following treatment of acute lymphoblastic leukemia in children Int J Hematol 1998 67: 397–401
Relling MV, Rubnitz JE, Rivera GK, Boyett JM, Hancock ML, Felix CA, Kun LE, Walter AW, Evans WE, Pui CH . High incidence of secondary brain tumours after radiotherapy and antimetabolites Lancet 1999 354: 34–39
Walter AW, Hancock ML, Pui CH, Hudson MM, Ochs JS, Rivera GK, Pratt CB, Boyett JM, Kun LE . Secondary brain tumors in children treated for acute lymphoblastic leukemia at St Jude Children's Research Hospital J Clin Oncol 1998 16: 3761–3767
Kaste SC, Hedlund G, Pratt CB . Malignant parotid tumors in patients previously treated for childhood cancer: clinical and imaging findings in eight cases Am J Roentgenol 1994 162: 655–659
Curtis RE, Rowlings PA, Deeg HJ, Shriner DA, Socie G, Travis LB, Horowitz MM, Witherspoon RP, Hoover RN, Sobocinski KA, Fraumeni JF Jr, Boice JD Jr . Solid cancers after bone marrow transplantation N Engl J Med 1997 336: 897–904
Deeg HJ, Socie G . Malignancies after hematopoietic stem cell transplantation: many questions, some answers Blood 1998 91: 1833–1844
Kolb HJ, Socie G, Duell T, Van Lint MT, Tichelli A, Apperley JF, Nekolla E, Ljungman P, Jacobsen N, van Weel M, Wick R, Weiss M, Prentice HG . Malignant neoplasms in long-term survivors of bone marrow transplantation Ann Intern Med 1999 131: 738–744
Socie G, Curtis RE, Deeg HJ, Sobocinski KA, Filipovich AH, Travis LB, Sullivan KM, Rowlings PA, Kingma DW, Banks PM, Travis WD, Witherspoon RP, Sanders J, Jaffe ES, Horowitz MM . New malignant diseases after allogeneic marrow transplantation for childhood acute leukemia J Clin Oncol 2000 18: 348–357
Gooley TA, Leisenring W, Crowley J, Storer BE . Estimation of failure probabilities in the presence of competing risks: new representations of old estimators Stat Med 1999 18: 695–706
Acknowledgements
This work was supported in part by grants CA-20180 and CA-21765 from the National Institutes of Health, by a Center of Excellence grant from the State of Tennessee, and by the American Lebanese Syrian Associated Charities (ALSAC). We thank Dr Julia Cay Jones for scientific editing, Ms Annette Stone for data management, and Ms Pam Hays for registry management.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Leung, W., Ribeiro, R., Hudson, M. et al. Second malignancy after treatment of childhood acute myeloid leukemia. Leukemia 15, 41–45 (2001). https://doi.org/10.1038/sj.leu.2401948
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.leu.2401948
Keywords
This article is cited by
-
Medulloblastomas, CNS embryonal tumors, and cerebellar mutism syndrome: advances in care and future directions
Child's Nervous System (2023)
-
Two cases of phenotypic switch of primary cutaneous T cell lymphoma after treatment with an aggressive course and review of the literature
Virchows Archiv (2019)
-
Tongue cancer in young patients: case report of a 26-year-old patient
Head & Neck Oncology (2012)
-
Causes of death – other than progressive leukemia – in childhood acute lymphoblastic (ALL) and myeloid leukemia (AML): the Dutch Childhood Oncology Group experience
Leukemia (2005)
-
Growth Retardation and Bilateral Cataracts Followed by Anaplastic Meningioma 23 Years after High-Dose Cranial and Whole-Body Irradiation for Acute Lymphoblastic Leukemia: Case Report and Review of the Literature
Journal of Neuro-Oncology (2005)