Abstract
A 72-year-old male patient was initially diagnosed with essential thrombocythemia (ET), a Philadelphia chromosome-negative (Ph1−) chronic myeloproliferative disorder (CMPD), and was treated with hydroxyurea (HU). After 9 years of diagnosis of ET, his peripheral leukocytes gradually increased, while his platelet count showed a decrease. Bone marrow analysis disclosed Ph-positive chronic myelogenous leukemia (CML) in the chronic phase. Administration of imatinib mesylate (IM), a Bcr–Abl tyrosine kinase inhibitor (TKI), induced complete hematologic response in a month, but was discontinued after 4 months because of Grade 3 pleural effusion (PE). The treatment was switched to nilotinib which successfully induced a complete cytogenetic response (CCyR) after 5 months of TKI therapy and resolved the PE. Despite CCyR, however, ET recurred. Since then, the patient has been treated for 8 months with a combination of nilotinib and HU which has successfully controlled both CML and ET. This report includes a review of the characteristics of 15 reported cases with co-occurrence of CML and Bcr–Abl-negative CMPDs, including ours. Although rare, care needs to be taken since, despite the often similar clinical features of the two diseases, they require completely different treatments.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Finazzi G, Caruso V, Marchioli R, Capnist G, Chisesi T, Finelli C, et al. Acute leukemia in polycythemia vera: an analysis of 1638 patients enrolled in a prospective observational study. Blood. 2005;105:2664–70.
Radaelli F, Mazza R, Curioni E, Ciani A, Pomati M, Maiolo AT. Acute megakaryocytic leukemia in essential thrombocythemia: an unusual evolution? Eur J Haematol. 2002;69:108–11.
Mesa RA, Li CY, Ketterling RP, Schroeder GS, Knudson RA, Tefferi A. Leukemic transformation in myelofibrosis with myeloid metaplasia: a single-institution experience with 91 cases. Blood. 2005;105:973–7.
Dan K, Yamada T, Kimura Y, Usui N, Okamoto S, Sugihara T, et al. Clinical features of polycythemia vera and essential thrombocythemia in Japan: retrospective analysis of a nationwide survey by the Japanese Elderly Leukemia and Lymphoma Study Group. Int J Hematol. 2006;83:443–9.
Ohyashiki K, Kiguchi T, Ito Y, Fujimoto H, Gotoh A, Tauchi T, et al. Leukocytosis is linked to thrombosis at diagnosis, while JAK2 V617F mutation is associated with thrombosis during the course of essential thrombocythemia. Int J Hematol. 2008;87:446–8.
Wahlin A, Golovleva I. Emergence of Philadelphia positive chronic myeloid leukaemia during treatment with hydroxyurea for Philadelphia negative essential thrombocythaemia. Eur J Haematol. 2003;70:240–1.
Cesar JM, Cabello P, Ferro T, Navarro JL. Emergence of chronic myelogenous leukemia in a patient with primary thrombocythemia and absence of BCR/ABL rearrangement. Cancer Genet Cytogenet. 2006;167:74–7.
Curtin NJ, Campbell PJ, Green AR. The Philadelphia translocation and pre-existing myeloproliferative disorders. Br J Haematol. 2005;128:734–6.
Martin SE, DellaValla J. Untreated essential thrombocythemia evolving to biphenotypic leukemia, Philadelphia chromosome positive with monosomy 7: response to imatinib and reduced-intensity allogeneic stem cell transplant. Leukemia. 2005;19:1095–6.
Pardini S, Fozza C, Contini S, Rimini E, Ottaviani E, Amabile M, et al. A case of coexistence between JAK2V617F and BCR/ABL. Eur J Haematol. 2008;81:75–6.
Jallades L, Hayette S, Tigaud I, Johnston A, Coiffier B, Magaud JP, et al. Emergence of therapy-unrelated CML on a background of BCR-ABL-negative JAK2V617F-positive chronic idiopathic myelofibrosis. Leuk Res. 2008;32:1608–10.
Laibe S, Tadrist Z, Arnoulet C, Sainty D, Mozziconacci MJ. A myeloproliferative disorder may hide another one. Leuk Res. 2009;33:1133–6.
Bennett M, Chubar E. Chronic myeloid leukemia evolving after idiopathic myelofibrosis. Isr Med Assoc J. 2007;9:562–3.
Conchon MR, Costa JL, Novaes MM, Dorlhiac-Llacer PE, de Alencar Fischer C, hamone D, et al. Simultaneous detection of JAK2 V617F mutation and Bcr–Abl translocation in a patient with chronic myelogenous leukemia. Int J Hematol. 2008;88:243–5.
Krämer A, Reiter A, Kruth J, Erben P, Hochhaus A, Müller M, et al. JAK2–V617F mutation in a patient with Philadelphia-chromosome-positive chronic myeloid leukaemia. Lancet Oncol. 2007;8:658–60.
Cambier N, Renneville A, Cazaentre T, Soenen V, Cossement C, Giraudier S, et al. JAK2V617F-positive polycythemia vera and Philadelphia chromosome-positive chronic myeloid leukemia: one patient with two distinct myeloproliferative disorders. Leukemia. 2008;22:1454–5.
Ganti AK, Potti A, Mehdi SA. Chromosomal anomalies in two coexistent myeloproliferative disorders. Cancer Genet Cytogenet. 2003;145:172–5.
Mirza I, Frantz C, Clarke G, Voth AJ, Turner R. Transformation of polycythemia vera to chronic myelogenous leukemia. Arch Pathol Lab Med. 2007;131:1719–24.
Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005;352:1779–90.
Acknowledgments
We are grateful to Ms. M. Goto and Ms. R. Tanaka for their excellent technical supports. This work is partly supported by the grant from Japan Leukaemia Research Fund (to J.K.).
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Mizutani, S., Kuroda, J., Shimizu, D. et al. Emergence of chronic myelogenous leukemia during treatment for essential thrombocythemia. Int J Hematol 91, 516–521 (2010). https://doi.org/10.1007/s12185-010-0502-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12185-010-0502-3