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Development of acute myeloid leukemia in patients with untreated chronic lymphocytic leukemia

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Abstract

The development of acute myeloid leukemia (AML) in patients with untreated chronic lymphocytic leukemia (CLL) is rare. We experienced a 65-year-old man who developed AML with aberrant CD7 expression and monoallelic CEBPA mutation during watchful waiting for CLL. He failed to achieve complete response (CR) by standard induction therapy for AML. We retrospectively reviewed 27 patients who developed AML with untreated CLL published between 1973 and 2016. The median age at diagnosis of AML was 68 years, and the median duration between the diagnoses of AML and CLL was 4.2 years. Diagnosis of AML and CLL was made simultaneously in 16 patients. The CR rate of AML was 42.9%, and the median survival was only 1.5 months after the diagnosis of AML. Patients who achieved CR tended to survive longer than those who did not. Our results demonstrated that the development of AML in patients with untreated CLL was associated with a poor response to chemotherapy and an extremely poor prognosis.

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References

  1. Tadmor T, Polliack A (2012) Optimal management of older patients with chronic lymphocytic leukemia: some facts and principles guiding therapeutic choices. Blood Rev 26(1):15–23. doi:10.1016/j.blre.2011.09.002

    Article  CAS  PubMed  Google Scholar 

  2. Tsimberidou AM, Wen S, McLaughlin P, O'Brien S, Wierda WG, Lerner S, Strom S, Freireich EJ, Medeiros LJ, Kantarjian HM, Keating MJ (2009) Other malignancies in chronic lymphocytic leukemia/small lymphocytic lymphoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 27(6):904–910. doi:10.1200/jco.2008.17.5398

    Article  Google Scholar 

  3. Royle JA, Baade PD, Joske D, Girschik J, Fritschi L (2011) Second cancer incidence and cancer mortality among chronic lymphocytic leukaemia patients: a population-based study. Br J Cancer 105(7):1076–1081. doi:10.1038/bjc.2011.313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Tambaro FP, Garcia-Manero G, O'Brien SM, Faderl SH, Ferrajoli A, Burger JA, Pierce S, Wang X, Do KA, Kantarjian HM, Keating MJ, Wierda WG (2016) Outcomes for patients with chronic lymphocytic leukemia and acute leukemia or myelodysplastic syndrome. Leukemia 30(2):325–330. doi:10.1038/leu.2015.227

    Article  CAS  PubMed  Google Scholar 

  5. Wiernik PH (2004) Second neoplasms in patients with chronic lymphocytic leukemia. Curr Treat Options in Oncol 5(3):215–223

    Article  Google Scholar 

  6. DeFilipp Z, Huynh DV, Fazal S, Sahovic E (2012) Allogeneic stem cell transplantation for acute myeloid leukemia with del (7q) following untreated chronic lymphocytic leukemia. Hematol Oncol Stem Cell Ther 5(3):165–168. doi:10.5144/1658-3876.2012.165

    Article  PubMed  Google Scholar 

  7. Swerdlow SH, Harris NL, Campo E (eds) (2008) WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon IARC,

    Google Scholar 

  8. Kanda Y (2013) Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 48(3):452–458. doi:10.1038/bmt.2012.244

    Article  CAS  PubMed  Google Scholar 

  9. Roberts PD, Forster PM (1973) Chronic lymphocytic leukaemia associated with acute myelomonocytic leukaemia. Br J Haematol 25(2):203–206

    Article  CAS  PubMed  Google Scholar 

  10. Adams PB, Cornell FN, Ding JC, Cooper IA (1977) Characterization of tumour cells in concomitant chronic lymphocytic leukaemia and acute monocytic leukaemia. Am J Hematol 2(3):271–282

    Article  CAS  PubMed  Google Scholar 

  11. Lawlor E, McCann SR, Whelan A, Greally J, Temperley IJ (1979) Acute myeloid leukaemia occurring in untreated chronic lymphatic leukaemia. Br J Haematol 43(3):369–373

    Article  CAS  PubMed  Google Scholar 

  12. Stern N, Shemesh J, Ramot B (1981) Chronic lymphatic leukemia terminating in acute myeloid leukemia: review of the literature. Cancer 47(7):1849–1851

    Article  CAS  PubMed  Google Scholar 

  13. Wallis JP, Joyner MV (1986) Acute myeloid leukaemia developing in a patient with longstanding untreated chronic lymphocytic leukaemia. Acta Haematol 75(4):229–231

    Article  CAS  PubMed  Google Scholar 

  14. Conlan MG, Mosher DF (1989) Concomitant chronic lymphocytic leukemia, acute myeloid leukemia, and thrombosis with protein C deficiency. Case report and review of the literature. Cancer 63(7):1398–1401

    Article  CAS  PubMed  Google Scholar 

  15. Caballero MD, Gonzalez M, Canizo MC, Orfao A, Nieto MJ, San Miguel JF (1992) Concomitant chronic lymphocytic leukemia (CLL) and acute myeloid leukemia. Complete remission of CLL achieved with high-dose cytosine arabinoside. Leukemia 6(8):856–858

    CAS  PubMed  Google Scholar 

  16. Tamul KR, Meyers DC, Bentley SA, Folds JD (1994) Two color flow cytometric analysis of concomitant acute myeloid leukemia and chronic lymphocytic leukemia. Cytometry 18(1):30–34. doi:10.1002/cyto.990180107

    Article  CAS  PubMed  Google Scholar 

  17. Lima M, Porto B, Rodrigues M, Teixeira MA, Coutinho J, Ribeiro AC, Malheiro MI, Justica B (1996) Cytogenetic findings in a patient presenting simultaneously with chronic lymphocytic leukemia and acute myeloid leukemia. Cancer Genet Cytogenet 87(1):38–40

    Article  CAS  PubMed  Google Scholar 

  18. Mateu R, Bellido M, Sureda A, Gonzalez Y, Rubiol E, Aventin A, Nomdedeu J (1997) Concomitant chronic lymphocytic leukemia and acute myeloid leukemia with an uncommon immunophenotype. Am J Hematol 56(4):281–287

    Article  CAS  PubMed  Google Scholar 

  19. Lai R, Arber DA, Brynes RK, Chan O, Chang KL (1999) Untreated chronic lymphocytic leukemia concurrent with or followed by acute myelogenous leukemia or myelodysplastic syndrome: a report of five cases and review of the literature. Am J Clin Pathol 111(3):373–378

    Article  CAS  PubMed  Google Scholar 

  20. Yenerel MN, Hatemi I, Keskin H (1999) Concomitant chronic lymphocytic leukemia and acute myeloid leukemia diagnosed by two color flow cytometric analysis. Haematologica 84(8):766–767

    CAS  PubMed  Google Scholar 

  21. Miller MK, Strauchen JA, Nichols KT, Phelps RG (2001) Concurrent chronic lymphocytic leukemia cutis and acute myelogenous leukemia cutis in a patient with untreated CLL. The American Journal of dermatopathology 23(4):334–340

    Article  CAS  PubMed  Google Scholar 

  22. Ornellas De Souza MH, de Souza FT, Diamond HR, Maioli MC, Pitanga Bacha PC, De Lucena SB (2001) Cytogenetic and immunophenotypic evidence of independent clonal origins of concomitant chronic lymphocytic leukaemia and acute myeloid leukaemia. Eur J Haematol 66(4):281–283

    Article  CAS  PubMed  Google Scholar 

  23. Gottardi M, Gattei V, Degan M, Bomben R, Zucchetto A, Tecchio C, Laurino L, Zanatta L, Dei Tos AP, Mordacchini M, Canal F, Gherlinzoni F (2006) Concomitant chronic lymphocytic leukemia and acute myeloid leukemia: evidence of simultaneous expansion of two independent clones. Leuk Lymphoma 47(5):885–889. doi:10.1080/10428190500404761

    Article  PubMed  Google Scholar 

  24. Lu CM, Murata-Collins JL, Wang E, Siddiqi I, Lawrence H (2006) Concurrent acute myeloid leukemia with inv(16)(p13.1q22) and chronic lymphocytic leukemia: molecular evidence of two separate diseases. Am J Hematol 81(12):963–968. doi:10.1002/ajh.20716

    Article  CAS  PubMed  Google Scholar 

  25. Pavlisa G, Kolonic SO, Minigo H, Kardum-Skelin I, Kardum-Paro MM, Jaksic B (2006) Acute leukemia in patients with untreated chronic lymphocytic leukemia: a report of two cases with remarkably similar time cluster. Leuk Lymphoma 47(5):950–952. doi:10.1080/10428190500403144

    Article  PubMed  Google Scholar 

  26. Carulli G, Marini A, Baccelli E, Lambelet P, Lari T, Azzara A (2007) Association of B-chronic lymphocytic leukemia and acute myeloid leukemia. Journal of experimental & clinical cancer research : CR 26(3):421–424

    CAS  Google Scholar 

  27. Katz JB, Curran AL, Zemba-Palko V, Dabrow MB, Denshaw-Burke MT (2010) Synchronous diagnosis of chronic lymphocytic leukemia and acute myeloid leukemia. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 28(35):e726–e728. doi:10.1200/jco.2010.30.2091

    Article  Google Scholar 

  28. Zhang R, Kim YM, Lu X, Wang X, Pang H, Li Y, Li S, Lee JY (2011) Characterization of a novel t(2;5;11) in a patient with concurrent AML and CLL: a case report and literature review. Cancer Genet 204(6):328–333. doi:10.1016/j.cancergen.2011.04.006

    Article  CAS  PubMed  Google Scholar 

  29. Al Mussaed E, Osman H, Elyamany G (2016) Simultaneous existence of acute myeloid leukemia and chronic lymphocytic leukemia: a case report. BMC Cancer 16(1):739. doi:10.1186/s12885-016-2780-5

    Article  PubMed  PubMed Central  Google Scholar 

  30. SEER Cancer Statistics Factsheets: National Cancer Institute. Bethesda, MD, [cited 2016 April]. http://seer.cancer.gov/statfacts/html/amyl.html.

  31. Dores GM, Devesa SS, Curtis RE, Linet MS, Morton LM (2012) Acute leukemia incidence and patient survival among children and adults in the United States, 2001–2007. Blood 119(1):34–43. doi:10.1182/blood-2011-04-347872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. [Internet] HmiE Northern and Yorkshire Cancer Registry and Information Service (NYCRIS) Haematological malignancies in England: Cancers Diagnosed 2001–2008. http://www.ncin.org.uk/view?rid=1787. Accessed January 2013

  33. Bhayat F, Das-Gupta E, Smith C, McKeever T, Hubbard R (2009) The incidence of and mortality from leukaemias in the UK: a general population-based study. BMC Cancer 9:252. doi:10.1186/1471-2407-9-252

    Article  PubMed  PubMed Central  Google Scholar 

  34. Kikushige Y, Miyamoto T (2014) Hematopoietic stem cell aging and chronic lymphocytic leukemia pathogenesis. Int J Hematol 100(4):335–340. doi:10.1007/s12185-014-1651-6

    Article  CAS  PubMed  Google Scholar 

  35. Kikushige Y, Miyamoto T (2015) Pre-malignant lymphoid cells arise from hematopoietic stem/progenitor cells in chronic lymphocytic leukemia. Int J Hematol 102(5):528–535. doi:10.1007/s12185-015-1740-1

    Article  CAS  PubMed  Google Scholar 

  36. Stengel A, Kern W, Haferlach T, Meggendorfer M, Fasan A, Haferlach C (2016) The impact of TP53 mutations and TP53 deletions on survival varies between AML, ALL, MDS and CLL: an analysis of 3307 cases. Leukemia. doi:10.1038/leu.2016.263

    PubMed Central  Google Scholar 

  37. Landau DA, Carter SL, Stojanov P, McKenna A, Stevenson K, Lawrence MS, Sougnez C, Stewart C, Sivachenko A, Wang L, Wan Y, Zhang W, Shukla SA, Vartanov A, Fernandes SM, Saksena G, Cibulskis K, Tesar B, Gabriel S, Hacohen N, Meyerson M, Lander ES, Neuberg D, Brown JR, Getz G, Wu CJ (2013) Evolution and impact of subclonal mutations in chronic lymphocytic leukemia. Cell 152(4):714–726. doi:10.1016/j.cell.2013.01.019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Staal FJ, Famili F, Garcia Perez L, Pike-Overzet K (2016) Aberrant Wnt Signaling in Leukemia. Cancers 8(9). doi:10.3390/cancers8090078

  39. Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62(1):10–29. doi:10.3322/caac.20138

    Article  PubMed  Google Scholar 

  40. Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, Goldstone AH, Wheatley K, Harrison CJ, Burnett AK (2010) Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood 116(3):354–365. doi:10.1182/blood-2009-11-254441

    Article  CAS  PubMed  Google Scholar 

  41. Tong WG, Wierda WG, Lin E, Kuang SQ, Bekele BN, Estrov Z, Wei Y, Yang H, Keating MJ, Garcia-Manero G (2010) Genome-wide DNA methylation profiling of chronic lymphocytic leukemia allows identification of epigenetically repressed molecular pathways with clinical impact. Epigenetics 5(6):499–508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Division of Hematology, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan

    Shoko Ito, Shin-ichiro Fujiwara, Kiyomi Mashima, Kento Umino, Daisuke Minakata, Hirofumi Nakano, Ryoko Yamasaki, Yasufumi Kawasaki, Miyuki Sugimoto, Masahiro Ashizawa, Chihiro Yamamoto, Kaoru Hatano, Kiyoshi Okazuka, Kazuya Sato, Iekuni Oh, Ken Ohmine, Takahiro Suzuki, Kazuo Muroi & Yoshinobu Kanda

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  1. Shoko Ito
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Correspondence to Yoshinobu Kanda.

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Ito, S., Fujiwara, Si., Mashima, K. et al. Development of acute myeloid leukemia in patients with untreated chronic lymphocytic leukemia. Ann Hematol 96, 719–724 (2017). https://doi.org/10.1007/s00277-017-2933-x

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