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International Journal of Hematology
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09-07-2022 | Thrombosis | Original Article

Clinical characteristics of Japanese patients with polycythemia vera: results of the JSH-MPN-R18 study

Authors: Yoko Edahiro, Tomoki Ito, Akihiko Gotoh, Mika Nakamae, Fumihiko Kimura, Michiaki Koike, Keita Kirito, Hideho Wada, Kensuke Usuki, Takayuki Tanaka, Takehiko Mori, Satoshi Wakita, Toshiki I. Saito, Akiko Kada, Akiko M. Saito, Kazuya Shimoda, Yuka Sugimoto, Toshiro Kurokawa, Akihiro Tomita, Yoshinori Hashimoto, Koichi Akashi, Itaru Matsumura, Katsuto Takenaka, Norio Komatsu

Published in: International Journal of Hematology | Issue 5/2022

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Abstract

The presence of a JAK2 V617F or JAK2 exon 12 mutation is one of the three major criteria listed for the diagnosis of polycythemia vera (PV) in the 2017 World Health Organization Classification. However, a nationwide study has not yet been conducted in Japan since the discovery of JAK2 mutations. Therefore, the Japanese Society of Hematology (JSH) retrospectively analyzed the clinical characteristics of 596 Japanese patients with PV diagnosed between April 2005 and March 2018. Among the 473 patients with complete data on JAK2 mutations available, 446 (94.3%) and 10 (2.1%) were positive for the JAK2 V617F and JAK2 exon 12 mutations, respectively. During a median follow-up of 46 months (range: 0–179 months), 47 (7.9%) deaths occurred. The major causes of death were secondary malignancies (23.4%), acute leukemia (12.8%), non-leukemic progressive disease (10.6%) and thrombotic (6.4%) and hemorrhagic complications (6.4%). Thrombotic and hemorrhagic events occurred during the clinical course in 4.0% (n = 24) and 3.5% (n = 21) of patients, respectively. These results show that the international PV prognostic score (age, venous thrombosis and leukocytosis) is applicable to Japanese patients with PV.
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Literature
1.
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(17):1779–90.PubMedCrossRef
2.
James C, Ugo V, Le Couedic JP, Staerk J, Delhommeau F, Lacout C, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005;434(7037):1144–8.PubMedCrossRef
3.
Levine RL, Wadleigh M, Cools J, Ebert BL, Wernig G, Huntly BJ, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005;7(4):387–97.PubMedCrossRef
4.
Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005;365(9464):1054–61.PubMedCrossRef
5.
Scott LM, Tong W, Levine RL, Scott MA, Beer PA, Stratton MR, et al. JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med. 2007;356(5):459–68.PubMedPubMedCentralCrossRef
6.
Titmarsh GJ, Duncombe AS, McMullin MF, O’Rorke M, Mesa R, De Vocht F, et al. How common are myeloproliferative neoplasms? A systematic review and meta-analysis. Am J Hematol. 2014;89(6):581–7.PubMedCrossRef
7.
Szuber N, Mudireddy M, Nicolosi M, Penna D, Vallapureddy RR, Lasho TL, et al. 3023 Mayo clinic patients with myeloproliferative neoplasms: risk-stratified comparison of survival and outcomes data among disease subgroups. Mayo Clin Proc. 2019;94(4):599–610.PubMedCrossRef
8.
Tefferi A, Rumi E, Finazzi G, Gisslinger H, Vannucchi AM, Rodeghiero F, et al. Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study. Leukemia. 2013;27(9):1874–81.PubMedPubMedCentralCrossRef
9.
Passamonti F, Rumi E, Pungolino E, Malabarba L, Bertazzoni P, Valentini M, et al. Life expectancy and prognostic factors for survival in patients with polycythemia vera and essential thrombocythemia. Am J Med. 2004;117(10):755–61.PubMedCrossRef
10.
Hultcrantz M, Kristinsson SY, Andersson TM, Landgren O, Eloranta S, Derolf AR, et al. Patterns of survival among patients with myeloproliferative neoplasms diagnosed in Sweden from 1973 to 2008: a population-based study. J Clin Oncol. 2012;30(24):2995–3001.PubMedPubMedCentralCrossRef
11.
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(5):443–9.PubMedCrossRef
12.
Rungjirajittranon T, Owattanapanich W, Ungprasert P, Siritanaratkul N, Ruchutrakool T. A systematic review and meta-analysis of the prevalence of thrombosis and bleeding at diagnosis of Philadelphia-negative myeloproliferative neoplasms. BMC Cancer. 2019;19(1):184.PubMedPubMedCentralCrossRef
13.
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. (2017) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Revised 4th edn. Lyon, France: IARC.
14.
Edahiro Y, Morishita S, Takahashi K, Hironaka Y, Yahata Y, Sunami Y, et al. JAK2V617F mutation status and allele burden in classical Ph-negative myeloproliferative neoplasms in Japan. Int J Hematol. 2014;99(5):625–34.PubMedCrossRef
15.
Kamiunten A, Shide K, Kameda T, Sekine M, Kubuki Y, Ito M, et al. Thrombohemorrhagic events, disease progression, and survival in polycythemia vera and essential thrombocythemia: a retrospective survey in Miyazaki prefecture. Japan Int J Hematol. 2018;107(6):681–8.PubMedCrossRef
16.
Komatsu N, Jun G, Yonezu T, Ohashi Y. Real-world, retrospective study evaluating thromboembolic events, associated risk factors, and health-care resource utilization in Japanese patients with polycythemia vera. Int J Hematol. 2020;112(2):176–84.PubMedCrossRef
17.
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon, France: IARC Press; 2008.
18.
Van Buuren S, Brand JPL, Groothuis-Oudshoorn CGM, Rubin DB. Fully conditional specification in multivariate imputation. J Stat Comput Simul. 2006;76(12):1049–64.CrossRef
19.
Rubin DB. Multiple imputation for nonresponse in surveys. New York: John Wiley & Sons Inc; 1987.CrossRef
20.
Tefferi A, Lavu S, Mudireddy M, Lasho TL, Finke CM, Gangat N, et al. JAK2 exon 12 mutated polycythemia vera: Mayo-Careggi MPN Alliance study of 33 consecutive cases and comparison with JAK2V617F mutated disease. Am J Hematol. 2018;93(4):E93–6.PubMedCrossRef
21.
Tondeur S, Paul F, Riou J, Mansier O, Ranta D, Le Clech L, et al. Long-term follow-up of JAK2 exon 12 polycythemia vera: a French Intergroup of Myeloproliferative Neoplasms (FIM) study. Leukemia. 2021;35(3):871–5.PubMedCrossRef
22.
Barbui T, Barosi G, Birgegard G, Cervantes F, Finazzi G, Griesshammer M, et al. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet. J Clin Oncol. 2011;29(6):761–70.PubMedPubMedCentralCrossRef
23.
Tefferi A, Spivak JL. Polycythemia vera: scientific advances and current practice. Semin Hematol. 2005;42(4):206–20.PubMedCrossRef
24.
Shimoda K, Takahashi N, Kirito K, Iriyama N, Kawaguchi T, Kizaki M. JSH Practical Guidelines for Hematological Malignancies, 2018: I. Leukemia-4. Chronic myeloid leukemia (CML)/myeloproliferative neoplasms (MPN). Int J Hematol. 2020;112(3):268–91.
25.
Tefferi A, Guglielmelli P, Larson DR, Finke C, Wassie EA, Pieri L, et al. Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis. Blood. 2014;124(16):2507–13; quiz 615.
26.
Abdulkarim K, Ridell B, Johansson P, Kutti J, Safai-Kutti S, Andréasson B. The impact of peripheral blood values and bone marrow findings on prognosis for patients with essential thrombocythemia and polycythemia vera. Eur J Haematol. 2011;86(2):148–55.PubMedCrossRef
27.
Hultcrantz M, Björkholm M, Dickman PW, Landgren O, Derolf ÅR, Kristinsson SY, et al. Risk for arterial and venous thrombosis in patients with myeloproliferative neoplasms: a population-based cohort study. Ann Intern Med. 2018;168(5):317–25.PubMedPubMedCentralCrossRef
28.
Vannucchi AM. Insights into the pathogenesis and management of thrombosis in polycythemia vera and essential thrombocythemia. Intern Emerg Med. 2010;5(3):177–84.PubMedCrossRef
29.
Marchioli R, Finazzi G, Landolfi R, Kutti J, Gisslinger H, Patrono C, et al. Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. J Clin Oncol. 2005;23(10):2224–32.PubMedCrossRef
30.
Marchioli R, Finazzi G, Specchia G, Cacciola R, Cavazzina R, Cilloni D, et al. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med. 2013;368(1):22–33.PubMedCrossRef
31.
Barbui T, Masciulli A, Marfisi MR, Tognoni G, Finazzi G, Rambaldi A, et al. White blood cell counts and thrombosis in polycythemia vera: a subanalysis of the CYTO-PV study. Blood. 2015;126(4):560–1.PubMedCrossRef
32.
Barbui T, Vannucchi AM, Carobbio A, Rumi E, Finazzi G, Gisslinger H, et al. The effect of arterial hypertension on thrombosis in low-risk polycythemia vera. Am J Hematol. 2017;92(1):E5-e6.PubMedCrossRef
33.
Barbui T, Carobbio A, Rumi E, Finazzi G, Gisslinger H, Rodeghiero F, et al. In contemporary patients with polycythemia vera, rates of thrombosis and risk factors delineate a new clinical epidemiology. Blood. 2014;124(19):3021–3.PubMedCrossRef
34.
Cerquozzi S, Barraco D, Lasho T, Finke C, Hanson CA, Ketterling RP, et al. Risk factors for arterial versus venous thrombosis in polycythemia vera: a single center experience in 587 patients. Blood Cancer J. 2017;7(12):662.PubMedPubMedCentralCrossRef
35.
Barbui T, Tefferi A, Vannucchi AM, Passamonti F, Silver RT, Hoffman R, et al. Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet. Leukemia. 2018;32(5):1057–69.PubMedPubMedCentralCrossRef
36.
Cerquozzi S, Tefferi A. Blast transformation and fibrotic progression in polycythemia vera and essential thrombocythemia: a literature review of incidence and risk factors. Blood Cancer J. 2015;5: e366.PubMedPubMedCentralCrossRef
37.
Gangat N, Strand J, Li CY, Wu W, Pardanani A, Tefferi A. Leucocytosis in polycythaemia vera predicts both inferior survival and leukaemic transformation. Br J Haematol. 2007;138(3):354–8.PubMedCrossRef
38.
Barbui T, Thiele J, Passamonti F, Rumi E, Boveri E, Randi ML, et al. Initial bone marrow reticulin fibrosis in polycythemia vera exerts an impact on clinical outcome. Blood. 2012;119(10):2239–41.PubMedCrossRef
39.
Passamonti F, Rumi E, Pietra D, Elena C, Boveri E, Arcaini L, et al. A prospective study of 338 patients with polycythemia vera: the impact of JAK2 (V617F) allele burden and leukocytosis on fibrotic or leukemic disease transformation and vascular complications. Leukemia. 2010;24(9):1574–9.PubMedCrossRef
40.
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(7):2664–70.PubMedCrossRef
41.
Barbui T, Vannucchi AM, Finazzi G, Finazzi MC, Masciulli A, Carobbio A, et al. A reappraisal of the benefit-risk profile of hydroxyurea in polycythemia vera: a propensity-matched study. Am J Hematol. 2017;92(11):1131–6.PubMedCrossRef
42.
Mesa RA, Jamieson C, Bhatia R, Deininger MW, Fletcher CD, Gerds AT, et al. NCCN guidelines insights: myeloproliferative neoplasms, version 2.2018. J Natl Compr Canc Netw. 2017;15(10):1193–207.PubMedCrossRef
43.
McMullin MF, Harrison CN, Ali S, Cargo C, Chen F, Ewing J, et al. A guideline for the diagnosis and management of polycythaemia vera. A British Society for haematology guideline. Br J Haematol. 2019;184(2):176–91.PubMedCrossRef
44.
Chou YS, Gau JP, Yu YB, Pai JT, Hsiao LT, Liu JH, et al. Leukocytosis in polycythemia vera and splenomegaly in essential thrombocythemia are independent risk factors for hemorrhage. Eur J Haematol. 2013;90(3):228–36.PubMedCrossRef
45.
Duangnapasatit B, Rattarittamrong E, Rattanathammethee T, Hantrakool S, Chai-Adisaksopha C, Tantiworawit A, et al. Clinical manifestations and risk factors for complications of Philadelphia chromosome-negative Myeloproliferative neoplasms. Asian Pac J Cancer Prev. 2015;16(12):5013–8.PubMedCrossRef
46.
Kaifie A, Kirschner M, Wolf D, Maintz C, Hänel M, Gattermann N, et al. Bleeding, thrombosis, and anticoagulation in myeloproliferative neoplasms (MPN): analysis from the German SAL-MPN-registry. J Hematol Oncol. 2016;9:18.PubMedPubMedCentralCrossRef
47.
Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013;369(25):2379–90.PubMedCrossRef
48.
Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med. 2013;369(25):2391–405.PubMedPubMedCentralCrossRef
49.
Broséus J, Park JH, Carillo S, Hermouet S, Girodon F. Presence of calreticulin mutations in JAK2-negative polycythemia vera. Blood. 2014;124(26):3964–6.PubMedCrossRef
50.
Elf S, Abdelfattah NS, Chen E, Perales-Paton J, Rosen EA, Ko A, et al. Mutant calreticulin requires both its mutant C-terminus and the thrombopoietin receptor for oncogenic transformation. Cancer Discov. 2016;6(4):368–81.PubMedPubMedCentralCrossRef
51.
Okabe M, Yamaguchi H, Usuki K, Kobayashi Y, Kawata E, Kuroda J, et al. Clinical features of Japanese polycythemia vera and essential thrombocythemia patients harboring CALR, JAK2V617F, JAK2Ex12del, and MPLW515L/K mutations. Leuk Res. 2016;40:68–76.PubMedCrossRef
Metadata
Title
Clinical characteristics of Japanese patients with polycythemia vera: results of the JSH-MPN-R18 study
Authors
Yoko Edahiro
Tomoki Ito
Akihiko Gotoh
Mika Nakamae
Fumihiko Kimura
Michiaki Koike
Keita Kirito
Hideho Wada
Kensuke Usuki
Takayuki Tanaka
Takehiko Mori
Satoshi Wakita
Toshiki I. Saito
Akiko Kada
Akiko M. Saito
Kazuya Shimoda
Yuka Sugimoto
Toshiro Kurokawa
Akihiro Tomita
Yoshinori Hashimoto
Koichi Akashi
Itaru Matsumura
Katsuto Takenaka
Norio Komatsu
Publication date
09-07-2022
Publisher
Springer Nature Singapore
Published in
International Journal of Hematology / Issue 5/2022
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-022-03412-x

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