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Published in: Annals of Hematology 5/2017

01-05-2017 | Original Article

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

Authors: 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

Published in: Annals of Hematology | Issue 5/2017

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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.
Literature
2.
go back to reference 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 CrossRef 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 CrossRef
4.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
5.
go back to reference Wiernik PH (2004) Second neoplasms in patients with chronic lymphocytic leukemia. Curr Treat Options in Oncol 5(3):215–223CrossRef Wiernik PH (2004) Second neoplasms in patients with chronic lymphocytic leukemia. Curr Treat Options in Oncol 5(3):215–223CrossRef
6.
7.
go back to reference Swerdlow SH, Harris NL, Campo E (eds) (2008) WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon IARC, Swerdlow SH, Harris NL, Campo E (eds) (2008) WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon IARC,
9.
go back to reference Roberts PD, Forster PM (1973) Chronic lymphocytic leukaemia associated with acute myelomonocytic leukaemia. Br J Haematol 25(2):203–206CrossRefPubMed Roberts PD, Forster PM (1973) Chronic lymphocytic leukaemia associated with acute myelomonocytic leukaemia. Br J Haematol 25(2):203–206CrossRefPubMed
10.
go back to reference 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):271–282CrossRefPubMed 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):271–282CrossRefPubMed
11.
go back to reference 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):369–373CrossRefPubMed 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):369–373CrossRefPubMed
12.
go back to reference Stern N, Shemesh J, Ramot B (1981) Chronic lymphatic leukemia terminating in acute myeloid leukemia: review of the literature. Cancer 47(7):1849–1851CrossRefPubMed Stern N, Shemesh J, Ramot B (1981) Chronic lymphatic leukemia terminating in acute myeloid leukemia: review of the literature. Cancer 47(7):1849–1851CrossRefPubMed
13.
go back to reference Wallis JP, Joyner MV (1986) Acute myeloid leukaemia developing in a patient with longstanding untreated chronic lymphocytic leukaemia. Acta Haematol 75(4):229–231CrossRefPubMed Wallis JP, Joyner MV (1986) Acute myeloid leukaemia developing in a patient with longstanding untreated chronic lymphocytic leukaemia. Acta Haematol 75(4):229–231CrossRefPubMed
14.
go back to reference 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):1398–1401CrossRefPubMed 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):1398–1401CrossRefPubMed
15.
go back to reference 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):856–858PubMed 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):856–858PubMed
17.
go back to reference 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):38–40CrossRefPubMed 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):38–40CrossRefPubMed
18.
go back to reference 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):281–287CrossRefPubMed 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):281–287CrossRefPubMed
19.
go back to reference 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):373–378CrossRefPubMed 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):373–378CrossRefPubMed
20.
go back to reference 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):766–767PubMed 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):766–767PubMed
21.
go back to reference 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):334–340CrossRefPubMed 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):334–340CrossRefPubMed
22.
go back to reference 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):281–283CrossRefPubMed 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):281–283CrossRefPubMed
23.
go back to reference 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 CrossRefPubMed 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/​1042819050040476​1 CrossRefPubMed
24.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
25.
go back to reference 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 CrossRefPubMed 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/​1042819050040314​4 CrossRefPubMed
26.
go back to reference 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 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
27.
go back to reference 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 CrossRef 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 CrossRef
36.
go back to reference 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 PubMedCentral 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 PubMedCentral
37.
go back to reference 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 CrossRefPubMedPubMedCentral 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 CrossRefPubMedPubMedCentral
40.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
41.
go back to reference 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):499–508CrossRefPubMedPubMedCentral 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):499–508CrossRefPubMedPubMedCentral
Metadata
Title
Development of acute myeloid leukemia in patients with untreated chronic lymphocytic leukemia
Authors
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
Publication date
01-05-2017
Publisher
Springer Berlin Heidelberg
Published in
Annals of Hematology / Issue 5/2017
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-017-2933-x

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