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Acute myeloid leukemia

Defining AML and MDS second cancer risk dynamics after diagnoses of first cancers treated or not with radiation

Leukemia volume 30, pages 285–294 (2016)Cite this article

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Abstract

Risks of acute myeloid leukemia (AML) and/or myelodysplastic syndromes (MDS) are known to increase after cancer treatments. Their rise-and-fall dynamics and their associations with radiation have, however, not been fully characterized. To improve risk definition we developed SEERaBomb R software for Surveillance, Epidemiology and End Results second cancer analyses. Resulting high-resolution relative risk (RR) time courses were compared, where possible, to results of A-bomb survivor analyses. We found: (1) persons with prostate cancer receiving radiation therapy have increased RR of AML and MDS that peak in 1.5–2.5 years; (2) persons with non-Hodgkin lymphoma (NHL), lung and breast first cancers have the highest RR for AML and MDS over the next 1–12 years. These increased RR are radiation specific for lung and breast cancer but not for NHL; (3) AML latencies were brief compared to those of A-bomb survivors; and (4) there was a marked excess risk of acute promyelocytic leukemia in persons receiving radiation therapy. Knowing the type of first cancer, if it was treated with radiation, the interval from first cancer diagnosis to developing AML or MDS, and the type of AML, can improve estimates of whether AML or MDS cases developing in this setting are due to background versus other processes.

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References

  1. Gale RP, Bennett JM, Hoffman FO, Therapy-related AML . a slip of the lip can sink a ship. Leuk Res 2014; 38: 418–420.

    Article  Google Scholar 

  2. SEER. Surveillance, Epidemiology, and End Results (SEER) Program Research Data (1973–2012), National Cancer Institute, DCCPS, Surveillance Research Program, Surveillance Systems Branch http://www.seer.cancer.gov, released April 2015, based on the November 2014 submission. 2015.

  3. Mukherjee S, Reddy CA, Ciezki JP, Abdel-Wahab M, Tiu RV, Copelan E et al. Risk for developing myelodysplastic syndromes in prostate cancer patients definitively treated with radiation. J Natl Cancer Inst 2014; 106: djt462.

    Article  Google Scholar 

  4. Armitage JO, Carbone PP, Connors JM, Levine A, Bennett JM, Kroll S . Treatment-related myelodysplasia and acute leukemia in non-Hodgkin's lymphoma patients. J Clin Oncol 2003; 21: 897–906.

    Article  Google Scholar 

  5. Kaplan HG, Malmgren JA, Atwood MK . Increased incidence of myelodysplastic syndrome and acute myeloid leukemia following breast cancer treatment with radiation alone or combined with chemotherapy: a registry cohort analysis 1990–2005. BMC Cancer 2011; 11: 260.

    Article  Google Scholar 

  6. Berrington de Gonzalez A, Curtis RE, Kry SF, Gilbert E, Lamart S, Berg CD et al. Proportion of second cancers attributable to radiotherapy treatment in adults: a cohort study in the US SEER cancer registries. Lancet Oncol 2011; 12: 353–360.

    Article  Google Scholar 

  7. Morton LM, Dores GM, Tucker MA, Kim CJ, Onel K, Gilbert ES et al. Evolving risk of therapy-related acute myeloid leukemia following cancer chemotherapy among adults in the United States, 1975-2008. Blood 2013; 121: 2996–3004.

    Article  CAS  Google Scholar 

  8. Hsu WL, Preston DL, Soda M, Sugiyama H, Funamoto S, Kodama K et al. The incidence of leukemia, lymphoma and multiple myeloma among atomic bomb survivors: 1950-2001. Radiat Res 2013; 179: 361–382.

    Article  CAS  Google Scholar 

  9. Iwanaga M, Hsu WL, Soda M, Takasaki Y, Tawara M, Joh T et al. Risk of myelodysplastic syndromes in people exposed to ionizing radiation: a retrospective cohort study of Nagasaki atomic bomb survivors. J Clin Oncol 2011; 29: 428–434.

    Article  Google Scholar 

  10. Preston DL, Kusumi S, Tomonaga M, Izumi S, Ron E, Kuramoto A et al. Cancer incidence in atomic bomb survivors Part III. Leukemia, lymphoma and multiple myeloma, 1950-1987. Radiat Res 1994; 2/1994 137: S68–S97.

    Article  CAS  Google Scholar 

  11. Haferlach T, Nagata Y, Grossmann V, Okuno Y, Bacher U, Nagae G et al. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia 2014; 28: 241–247.

    Article  CAS  Google Scholar 

  12. Cancer Genome Atlas Research N. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med 2013; 368: 2059–2074.

    Article  Google Scholar 

  13. Hastie T, Tibshirani R . Generalized additive models for medical research. Stat Methods Med Res 1995; 4: 187–196.

    Article  CAS  Google Scholar 

  14. Ihaka R, Gentleman R . R: a language for data analysis and graphics. J Comput Graph Stat 1996; 5: 299–314.

    Google Scholar 

  15. Garwood F . Fiducial limits for the Poisson distribution. Biometrika 1936; 28: 437–442.

    Google Scholar 

  16. Matsuo T, Tomonaga M, Bennett JM, Kuriyama K, Imanaka F, Kuramoto A et al. Reclassification of leukemia among A-bomb survivors in Nagasaki using French-American-British (FAB) classification for acute leukemia. Jpn J Clin Oncol 1988; 18: 91–96.

    CAS  PubMed  Google Scholar 

  17. Radivoyevitch T, Ramsey MJ, Tucker JD . Estimation of the target stem-cell population size in chronic myeloid leukemogenesis. Radiat Environ Biophys 1999; 38: 201–206.

    Article  CAS  Google Scholar 

  18. Tomonaga M . Leukaemia in Nagasaki atomic bomb survivors from 1945 through 1959. Bull World Health Organ 1962; 26: 619–631.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Radivoyevitch T, Kozubek S, Sachs RK . Biologically based risk estimation for radiation-induced CML. Inferences from BCR and ABL geometric distributions. Radiat Environ Biophys 2001; 40: 1–9.

    Article  CAS  Google Scholar 

  20. Radivoyevitch T, Hlatky L, Landaw J, Sachs RK . Quantitative modeling of chronic myeloid leukemia: insights from radiobiology. Blood 2012; 119: 4363–4371.

    Article  CAS  Google Scholar 

  21. Radivoyevitch T, Jankovic GM, Tiu RV, Saunthararajah Y, Jackson RC, Hlatky LR et al. Sex differences in the incidence of chronic myeloid leukemia. Radiat Environ Biophys 2014; 53: 55–63.

    Article  Google Scholar 

  22. Gale RP, Hlatky L, Sachs RK, Radivoyevitch T . Why is there so much therapy-related AML and MDS and so little therapy-related CML? Leuk Res 2014; 38: 1162–1164.

    Article  Google Scholar 

  23. Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman PV, Mar BG et al. Age-Related Clonal Hematopoiesis Associated with Adverse Outcomes. N Engl J Med 2014; 37: 2488–2498.

    Article  Google Scholar 

  24. Varadarajan R, Ford L, Sait SN, Block AW, Barcos M, Wallace PK et al. Metachronous and synchronous presentation of acute myeloid leukemia and lung cancer. Leuk Res 2009; 33: 1208–1211.

    Article  Google Scholar 

  25. Pirani M, Marcheselli R, Marcheselli L, Bari A, Federico M, Sacchi S . Risk for second malignancies in non-Hodgkin's lymphoma survivors: a meta-analysis. Ann Oncol 2011; 22: 1845–1858.

    Article  CAS  Google Scholar 

  26. Wallner LP, Wang R, Jacobsen SJ, Haque R . Androgen deprivation therapy for treatment of localized prostate cancer and risk of second primary malignancies. Cancer Epidemiol Biomarkers Prev 2013; 22: 313–316.

    Article  CAS  Google Scholar 

  27. Carreras E, Kovats S . Girl power: estrogen promotes HSC self-renewal. Cell Stem Cell 2014; 14: 137–138.

    Article  CAS  Google Scholar 

  28. Nakada D, Oguro H, Levi BP, Ryan N, Kitano A, Saitoh Y et al. Oestrogen increases haematopoietic stem-cell self-renewal in females and during pregnancy. Nature 2014; 505: 555–558.

    Article  CAS  Google Scholar 

  29. Thompson DE, Mabuchi K, Ron E, Soda M, Tokunaga M, Ochikubo S et al. Cancer incidence in atomic bomb survivors. Part II: Solid tumors, 1958–1987. Radiat Res 1994; 137: S17–S67.

    Article  CAS  Google Scholar 

  30. Cox DR . Regression models and life tables. J R Stat Soc B 1972; 34: 187–220.

    Google Scholar 

  31. Fine JP, Gray RJ . A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 1999; 94: 496–509.

    Article  Google Scholar 

Download references

Acknowledgements

We thank Drs Li Li and Cornelis Van Noorden for suggestions and the R community for software. The content of this report is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. We used data obtained from the Radiation Effects Research Foundation (RERF), Hiroshima and Nagasaki, Japan. RERF is a public interest foundation funded by the Japanese Ministry of Health, Labour and Welfare (MHLW) and the U.S. Department of Energy (DOE), the latter in part through DOE award DE-HS0000031 to the National Academy of Sciences. Conclusions in this report are those of the authors and do not necessarily reflect the scientific judgment of RERF or its funding agencies. This work was supported by: the Cleveland Clinic, the National Aeronautics and Space Administration (NNJ13ZSA001N) (TR), the National Institute for Health Research Biomedical Research Centre funding scheme (RPG), and the Academic Medical Center of Amsterdam (RJM).

Author contributions

JPM initiated and motivated the study. TR developed the software and wrote the first draft. RKS, DJB and RPG helped with the A-bomb data analyses. RJM helped with SEER*Stat comparisons. RPG, JPM, MAS, BTH, RJM, HEC and SM contributed feedback/guidance and writing.

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Authors and Affiliations

  1. Department of Quantitative Health Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA

    T Radivoyevitch

  2. Department of Mathematics, University of California, Berkeley, CA, USA

    R K Sachs

  3. Department of Medicine, Section of Hematology, Imperial College London, London, UK

    R P Gale

  4. Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    R J Molenaar

  5. Department of Translational Hematology and Oncology Research, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA

    R J Molenaar & J P Maciejewski

  6. Department of Radiation Oncology, Center for Radiological Research, Columbia University, New York, NY, USA

    D J Brenner

  7. Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA

    B T Hill, M E Kalaycio, H E Carraway, S Mukherjee, M A Sekeres & J P Maciejewski

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  1. T Radivoyevitch
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Correspondence to T Radivoyevitch.

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Radivoyevitch, T., Sachs, R., Gale, R. et al. Defining AML and MDS second cancer risk dynamics after diagnoses of first cancers treated or not with radiation. Leukemia 30, 285–294 (2016). https://doi.org/10.1038/leu.2015.258

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