今日の臨床サポート

本態性血小板血症

著者: 桐戸敬太 山梨大学医学部附属病院 血液・腫瘍内科

監修: 木崎昌弘 埼玉医科大学総合医療センター

著者校正/監修レビュー済:2021/09/01
参考ガイドライン:
  1. 日本血液学会:造血器腫瘍診療ガイドライン2018年補訂版
患者向け説明資料

概要・推奨   

  1. 本態性血小板血症における血栓症のリスクとしては、年齢(60歳以上)および血栓・出血の既往の存在の2つが確立されている(推奨度1)
  1. 上記に加えて糖尿病、高血圧症および脂質異常症などの心血管リスク因子やJAK2V617F変異の有無を取り入れた新たなリスク分類IPSET-TInternational prognostic score for ET, thrombosisおよびRevised-IPEST-Tが提唱されている(推奨度3
  1. 次世代シーケンサを用いた解析では、SRSF2, SF3B1, U2AF1およびTP53のいずれかに変異を有する症例では生命予後が不良であることが示された。この情報をも組み込んだ生命予後予測システムとして、MIPSS-ETが提唱された推奨度3)。
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要とな
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要と
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  1. 血小板数が著明に増加(100万以上)している症例においては、アスピリンの開始前にフォンウィルブランド因子活性を測定し、低下している場合には使用を控えることも推奨されている(推奨度2)。
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
桐戸敬太 : 講演料(ノバルティスファーマ株式会社,武田薬品工業)[2021年]
監修:木崎昌弘 : 講演料(ブリストル・マイヤーズスクイブ,ヤンセンファーマ,ノバルティスファーマ,セルジーン,MSD,小野薬品,武田薬品,大日本住友製薬),研究費・助成金など(武田薬品),奨学(奨励)寄付など(協和キリン,中外製薬,武田薬品,小野薬品,第一三共)[2021年]

改訂のポイント:
  1. 定期レビューを行った(新たな生命リスク評価システムとしてMIPSS-ETを追記した。一部の表現の修正

病態・疫学・診察

疾患情報  
  1. 本態性血小板血症(ET)は、多能性幹細胞に由来するクローナルな疾患で、骨髄増殖性腫瘍(MPN)に分類され、JAK2変異をはじめ遺伝子変異がその要因と考えられている。
  1. WHO2008年分類の診断基準からは、血小板数が45万以上に変更となった。
  1. JAK2V617F変異が約50%に、トロンボポエチンレセプターのc-MPLの変異が約10%の症例に、さらにCALR exon9変異が20~30%の症例に認められる。
  1. 診断においては、遺伝子変異解析に加えて骨髄病理解析が必須であり、特に、前線維芽期原発性骨髄線維症との鑑別においては不可欠である。
  1. 生命予後は健常者と比較しても相違はない。
  1. 治療の目標は血栓症や出血の回避である。
  1. 年齢と血栓症・出血の既往の2つが、血栓症・出血のリスク因子として確立されている。
  1. 上記リスク因子がない場合には、低用量アスピリンの治療を行う。リスク因子を有する群では、ハイドロキシウレアもしくはアナグレリドを用いた細胞減少療法を併用する。
  1. 若年(40~59歳)で血栓症・出血の既往や150万/μL以上の血小板増加などの所見を伴わない症例では、ハイドロキシウレアを使用すべきではない(推奨度1)。
問診・診察のポイント  
  1. 血小板増加症の鑑別を行う

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文献 

著者: Jürgen Thiele, Hans Michael Kvasnicka, Leonhard Müllauer, Veronika Buxhofer-Ausch, Bettina Gisslinger, Heinz Gisslinger
雑誌名: Blood. 2011 May 26;117(21):5710-8. doi: 10.1182/blood-2010-07-293761. Epub 2011 Mar 29.
Abstract/Text Controversy persists regarding the role of histopathology in the distinction between essential thrombocythemia (ET) and early-prefibrotic primary myelofi-brosis (PMF) presenting with thrombocythemia. To investigate the impact and reproducibility of bone marrow (BM) morphology according to the World Health Organization classification, 295 patients with the presumptive clinical diagnosis of either ET or early PMF were studied. Data of this cohort (Vienna group) were compared with 732 corresponding patients (Cologne group). Evaluating blindly (only age and gender known) BM specimens, the 2 groups of pathologists achieved an overall consensus of 78% regarding the total series and 88% concerning the discrimination between ET versus PMF. In 126 ET and 81 early PMF patients without pretreatment and complete documentation, a 90% concordance with the independently established clinical diagnosis was found. In 12 patients, overlapping of histopathology and some clinical findings between ET and polycythemia vera occurred. Contrasting ET, early PMF showed significant differences of presenting hematologic data and an unfavorable prognosis (estimated mean survival, 14 vs 21 years). Comparison of clinical and survival data of the Vienna cohort with the historical Cologne series revealed an overall congruence. This study highlights the impact of BM morphology for the differentiation between true vs false ET.

PMID 21447832  Blood. 2011 May 26;117(21):5710-8. doi: 10.1182/blood-2・・・
著者: Jerry L Spivak, Richard T Silver
雑誌名: Blood. 2008 Jul 15;112(2):231-9. doi: 10.1182/blood-2007-12-128454. Epub 2008 Apr 9.
Abstract/Text
PMID 18401028  Blood. 2008 Jul 15;112(2):231-9. doi: 10.1182/blood-200・・・
著者: Tiziano Barbui, Giovanni Barosi, Gunnar Birgegard, Francisco Cervantes, Guido Finazzi, Martin Griesshammer, Claire Harrison, Hans Carl Hasselbalch, Rudiger Hehlmann, Ronald Hoffman, Jean-Jacques Kiladjian, Nicolaus Kröger, Ruben Mesa, Mary F McMullin, Animesh Pardanani, Francesco Passamonti, Alessandro M Vannucchi, Andreas Reiter, Richard T Silver, Srdan Verstovsek, Ayalew Tefferi, European LeukemiaNet
雑誌名: J Clin Oncol. 2011 Feb 20;29(6):761-70. doi: 10.1200/JCO.2010.31.8436. Epub 2011 Jan 4.
Abstract/Text We present a review of critical concepts and produce recommendations on the management of Philadelphia-negative classical myeloproliferative neoplasms, including monitoring, response definition, first- and second-line therapy, and therapy for special issues. Key questions were selected according the criterion of clinical relevance. Statements were produced using a Delphi process, and two consensus conferences involving a panel of 21 experts appointed by the European LeukemiaNet (ELN) were convened. Patients with polycythemia vera (PV) and essential thrombocythemia (ET) should be defined as high risk if age is greater than 60 years or there is a history of previous thrombosis. Risk stratification in primary myelofibrosis (PMF) should start with the International Prognostic Scoring System (IPSS) for newly diagnosed patients and dynamic IPSS for patients being seen during their disease course, with the addition of cytogenetics evaluation and transfusion status. High-risk patients with PV should be managed with phlebotomy, low-dose aspirin, and cytoreduction, with either hydroxyurea or interferon at any age. High-risk patients with ET should be managed with cytoreduction, using hydroxyurea at any age. Monitoring response in PV and ET should use the ELN clinicohematologic criteria. Corticosteroids, androgens, erythropoiesis-stimulating agents, and immunomodulators are recommended to treat anemia of PMF, whereas hydroxyurea is the first-line treatment of PMF-associated splenomegaly. Indications for splenectomy include symptomatic portal hypertension, drug-refractory painful splenomegaly, and frequent RBC transfusions. The risk of allogeneic stem-cell transplantation-related complications is justified in transplantation-eligible patients whose median survival time is expected to be less than 5 years.

PMID 21205761  J Clin Oncol. 2011 Feb 20;29(6):761-70. doi: 10.1200/JC・・・
著者: G Finazzi, A Carobbio, J Thiele, F Passamonti, E Rumi, M Ruggeri, F Rodeghiero, M L Randi, I Bertozzi, A M Vannucchi, E Antonioli, H Gisslinger, V Buxhofer-Ausch, N Gangat, A Rambaldi, A Tefferi, T Barbui
雑誌名: Leukemia. 2012 Apr;26(4):716-9. doi: 10.1038/leu.2011.258. Epub 2011 Sep 16.
Abstract/Text In an international study of 1104 patients with essential thrombocythemia (ET), a histological review according to the 2008 World Health Organization (WHO) criteria confirmed ET in 891 patients (WHO-ET, 81%), and revised the diagnosis to prefibrotic primary myelofibrosis (PMF) in 180 patients (PMF, 16%). Major bleeding during follow-up occurred in 55 (6%) WHO-ET and 21 (12%) PMF patients (P = 0.009), at a rate of 0.79 and 1.39% patients per year, respectively, (P = 0.039). In a multivariable analysis, predictors of bleeding included diagnosis of PMF (P = 0.05; hazard ratio (HR) 1.74), leukocytosis (P = 0.04; HR 1.74), previous hemorrhage (P = 0.025; HR 2.35) and aspirin therapy (P=0.001; HR 3.16). The analysis restricted to patients with WHO-ET confirmed previous hemorrhage (P = 0.043; HR 1.92) and aspirin (P=0.027; HR 2.24) as independent risk factors. The current study reveals that major bleeding associated with thrombocytosis might be relatively specific to PMF, as opposed to WHO-defined ET. Furthermore, it shows that low-dose aspirin exacerbates these hemorrhagic events of PMF. In contrast, thrombocytosis per se was not a risk factor for bleeding; however, low-dose aspirin had a synergistic hemorrhagic effect unmasking the bleeding tendency of patients with extreme thrombocytosis. These observations carry significant therapeutic implications in these two WHO entities.

PMID 21926959  Leukemia. 2012 Apr;26(4):716-9. doi: 10.1038/leu.2011.2・・・
著者: Tiziano Barbui, Guido Finazzi, Alessandra Carobbio, Juergen Thiele, Francesco Passamonti, Elisa Rumi, Marco Ruggeri, Francesco Rodeghiero, Maria Luigia Randi, Irene Bertozzi, Heinz Gisslinger, Veronika Buxhofer-Ausch, Valerio De Stefano, Silvia Betti, Alessandro Rambaldi, Alessandro M Vannucchi, Ayalew Tefferi
雑誌名: Blood. 2012 Dec 20;120(26):5128-33; quiz 5252. doi: 10.1182/blood-2012-07-444067. Epub 2012 Oct 1.
Abstract/Text Accurate prediction of thrombosis in essential thrombocythemia (ET) provides the platform for prospective studies exploring preventive measures. Current risk stratification for thrombosis in ET is 2-tiered and considers low- and high-risk categories based on the respective absence or presence of either age > 60 years or history of thrombosis. In an international study of 891 patients with World Health Organization (WHO)-defined ET, we identified additional independent risk factors including cardiovascular risk factors and JAK2V617F. Accordingly, we assigned risk scores based on multivariable analysis-derived hazard ratios (HRs) to age > 60 years (HR = 1.5; 1 point), thrombosis history (HR = 1.9; 2 points), cardiovascular risk factors (HR = 1.6; 1 point), and JAK2V617F (HR = 2.0; 2 points) and subsequently devised a 3-tiered prognostic model (low-risk = < 2 points; intermediate-risk = 2 points; and high-risk = > 2 points) using a training set of 535 patients and validated the results in the remaining cohort (n = 356; internal validation set) and in an external validation set (n = 329). Considering all 3 cohorts (n = 1220), the 3-tiered new prognostic model (low-risk n = 474 vs intermediate-risk n = 471 vs high-risk n = 275), with a respective thrombosis risk of 1.03% of patients/y versus 2.35% of patients/y versus 3.56% of patients/y, outperformed the 2-tiered (low-risk 0.95% of patients/y vs high-risk 2.86% of patients/y) conventional risk stratification in predicting future vascular events.

PMID 23033268  Blood. 2012 Dec 20;120(26):5128-33; quiz 5252. doi: 10.・・・
著者: T Barbui, A M Vannucchi, V Buxhofer-Ausch, V De Stefano, S Betti, A Rambaldi, E Rumi, M Ruggeri, F Rodeghiero, M L Randi, I Bertozzi, H Gisslinger, G Finazzi, A Carobbio, J Thiele, F Passamonti, C Falcone, A Tefferi
雑誌名: Blood Cancer J. 2015 Nov 27;5:e369. doi: 10.1038/bcj.2015.94. Epub 2015 Nov 27.
Abstract/Text
PMID 26617062  Blood Cancer J. 2015 Nov 27;5:e369. doi: 10.1038/bcj.20・・・
著者: Ayalew Tefferi, Paola Guglielmelli, Terra L Lasho, Giacomo Coltro, Christy M Finke, Giuseppe G Loscocco, Benedetta Sordi, Natasha Szuber, Giada Rotunno, Annalisa Pacilli, Curtis A Hanson, Rhett P Ketterling, Animesh Pardanani, Naseema Gangat, Alessandro M Vannucchi
雑誌名: Br J Haematol. 2020 Apr;189(2):291-302. doi: 10.1111/bjh.16380. Epub 2020 Jan 16.
Abstract/Text Survival prediction in essential thrombocythaemia (ET) and polycythaemia vera (PV) is currently based on clinically-derived variables; we examined the possibility of integrating genetic information for predicting survival. To this end, 906 molecularly-annotated patients (416 Mayo Clinic; 490 University of Florence, Italy), including 502 ET and 404 PV, were recruited. Multivariable analysis identified spliceosome mutations to adversely affect overall (SF3B1, SRSF2 in ET and SRSF2 in PV) and myelofibrosis-free (U2AF1, SF3B1 in ET) survival; TP53 mutations predicted leukaemic transformation in ET; "adverse" mutations occurred in 51 (10%) ET and 8 (2%) PV patients. We confirmed the independent survival effect of adverse mutations [hazard ratio (HR) 2·4, 95% CI 1·6-3·5], age >60 years (6·6, 4·6-9·7), male sex (1·8, 1·3-2·4) and leukocytosis ≥11 × 109 /l (1·6, 1·1-2·2), in ET, and adverse mutations (7·8, 3·1-17·0), age >67 years (5·4, 3·6-8·1), leukocytosis ≥15 × 109 /l (2·8, 1·8-4·2) and thrombosis history (2·0, 1·4-2·9), in PV. HR-based risk point allocation allowed development of three-tiered mutation-enhanced international prognostic systems (MIPSS) which were validated in both cohorts and performance was shown to be superior to conventional scoring systems. Spliceosome mutations enhance survival prediction in ET and PV and identify patients at risk for fibrotic progression. TP53 mutations predict leukaemic transformation in ET.

© 2020 British Society for Haematology and John Wiley & Sons Ltd.
PMID 31945802  Br J Haematol. 2020 Apr;189(2):291-302. doi: 10.1111/bj・・・
著者: Yoshinori Hashimoto, Hirohisa Nakamae, Takayuki Tanaka, Hiromi Omura, Mirei Horiuchi, Takuro Yoshimura, Teruhito Takakuwa, Atsuko Mugitani, Asao Hirose, Mika Nakamae, Hideo Koh, Masayuki Hino
雑誌名: Eur J Haematol. 2018 Oct;101(4):508-513. doi: 10.1111/ejh.13136. Epub 2018 Aug 31.
Abstract/Text OBJECTIVE: We examined the prognostic factors to validate previous prognostic models for survival and thrombosis with large-scale data on Japanese patients with essential thrombocythemia (ET).
METHOD: We conducted a study in 352 patients with ET to validate previous prognostic models and search for new prognostic factors.
RESULTS: The International Prognostic Score for essential thrombocythemia (IPSET), the conventional risk classification and the International Prognostic Score for thrombosis in essential thrombocythemia (IPSET-T) were confirmed to be reproducible in Japanese patients. However, no significant difference was observed between the low-risk and intermediate-risk categories according to the revised IPSET-T, which does not allow direct comparison of the four risk groups. We reevaluated the risk using a modified revised IPSET-T, which was derived from the revised IPSET-T by scoring the factors as follows: one point for age > 60 years, two points for past history of thrombosis, two points for JAK2 gene mutation-positive; total points of 0 = very low risk, 1 =  low risk, 2 =  intermediate risk, 3 and above = high risk, with significantly different thrombosis-free survival.
CONCLUSION: The modified revised IPSET-T has been useful for 4-group stratification to predict a population that requires therapeutic intervention, irrespective of the treatment regimens.

© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
PMID 29971894  Eur J Haematol. 2018 Oct;101(4):508-513. doi: 10.1111/e・・・
著者: Federico Lussana, Sabrina Caberlon, Chiara Pagani, Pieter W Kamphuisen, Harry R Büller, Marco Cattaneo
雑誌名: Thromb Res. 2009 Sep;124(4):409-17. doi: 10.1016/j.thromres.2009.02.004. Epub 2009 Mar 18.
Abstract/Text INTRODUCTION: Many studies evaluated the association of V617F Jak-2 with the risk of thrombosis in patients with essential thrombocythaemia, but the results of these studies were inconsistent. Few studies evaluated the association of V617F Jak-2 mutation with the risk of thrombosis in patients with idiopathic myelofibrosis. Therefore, we performed a systematic review of the studies that assessed the risk of thrombosis associated with V617F Jak-2 in patients with ET or IM.
MATERIALS AND METHODS: We searched MEDLINE and EMBASE databases and reference lists of retrieved articles. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated for each trial and pooled.
RESULTS: We included 21 studies involving patients with essential thrombocythaemia and 6 studies patients with idiopathic myelofibrosis. In essential thrombocythaemia patients, V617F Jak-2 was associated with a significant increased risk of thrombosis (OR 1.92, 95% CI 1.45-2.53), both of venous (OR 2.49, 95% CI 1.71-3.61) and arterial (OR 1.77, 95% CI 1.29-2.43) vessels. In idiopathic myelofibrosis patients, the risk of thrombosis associated with V617F Jak-2 tended to be increased (OR 1.76, 95% CI 0.91-3.41).
CONCLUSIONS: Our systematic review suggests that V617F Jak-2 increases the risk of thrombosis in essential thrombocythaemia patients by about two fold while its role in idiopathic myelofibrosis patients is uncertain.

PMID 19299003  Thromb Res. 2009 Sep;124(4):409-17. doi: 10.1016/j.thro・・・
著者: Alberto Alvarez-Larrán, Francisco Cervantes, Arturo Pereira, Eduardo Arellano-Rodrigo, Virginia Pérez-Andreu, Juan-Carlos Hernández-Boluda, Ramón Ayats, Carlos Salvador, Ana Muntañola, Beatriz Bellosillo, Vicente Vicente, Luis Hernández-Nieto, Carmen Burgaleta, Blanca Xicoy, Carlos Besses
雑誌名: Blood. 2010 Aug 26;116(8):1205-10; quiz 1387. doi: 10.1182/blood-2010-01-263319. Epub 2010 May 27.
Abstract/Text The effectiveness of antiplatelet therapy as primary prophylaxis for thrombosis in low-risk essential thrombocythemia (ET) is not proven. In this study, the incidence rates of arterial and venous thrombosis were retrospectively analyzed in 300 low-risk patients with ET treated with antiplatelet drugs as monotherapy (n = 198) or followed with careful observation (n = 102). Follow-up was 802 and 848 person-years for antiplatelet therapy and observation, respectively. Rates of thrombotic events were 21.2 and 17.7 per 1000 person-years for antiplatelet therapy and observation, respectively (P = .6). JAK2 V617F-positive patients not receiving antiplatelet medication showed an increased risk of venous thrombosis (incidence rate ratio [IRR]: 4.0; 95% CI: 1.2-12.9; P = .02). Patients with cardiovascular risk factors had increased rates of arterial thrombosis while on observation (IRR: 2.5; 95% CI: 1.02-6.1; P = .047). An increased risk of major bleeding was observed in patients with platelet count greater than 1000 x 10(9)/L under antiplatelet therapy (IRR: 5.4; 95% CI: 1.7-17.2; P = .004). In conclusion, antiplatelet therapy reduces the incidence of venous thrombosis in patients with JAK2-positive ET and the rate of arterial thrombosis in patients with associated cardiovascular risk factors. In the remaining low-risk patients, this therapy is not effective as primary prophylaxis of thrombosis, and observation may be an adequate option.

PMID 20508163  Blood. 2010 Aug 26;116(8):1205-10; quiz 1387. doi: 10.1・・・
著者: N Gangat, A P Wolanskyj, R F McClure, C-Y Li, S Schwager, W Wu, A Tefferi
雑誌名: Leukemia. 2007 Feb;21(2):270-6. doi: 10.1038/sj.leu.2404500. Epub 2006 Dec 14.
Abstract/Text Unlike the case with thrombosis, prognostic models for survival and leukemic transformation (LT) in essential thrombocythemia (ET) are not available. Among 605 patients with ET seen at our institution and followed for a median of 84 months, 155 died and LT was documented in 20 patients (3.3%). In a multivariable analysis, hemoglobin level below normal (females<120 g/l; males<135 g/l) was identified as an independent risk factor for both inferior survival and LT. Additional risk factors for survival included age > or =60 years, leukocyte count> or =15 x 10(9)/l, smoking, diabetes mellitus and thrombosis. For LT, platelet count> or =1000 x 10(9)/l but not cytoreductive therapy was flagged as an additional independent risk factor. In fact, four of the 20 patients (20%) with LT were untreated previously. We used the above information to construct prognostic models that effectively discriminated among low-, intermediate- and high-risk groups with respective median survivals of 278, 200 and 111 months (P<0.0001), and LT rates of 0.4, 4.8 and 6.5% (P=0.0009) respectively. Presence of JAK2V617F did not impact either survival or LT and mutational frequency was similar among the different risk groups.

PMID 17170720  Leukemia. 2007 Feb;21(2):270-6. doi: 10.1038/sj.leu.240・・・
著者: Magnus Björkholm, Asa R Derolf, Malin Hultcrantz, Sigurdur Y Kristinsson, Charlotta Ekstrand, Lynn R Goldin, Björn Andreasson, Gunnar Birgegård, Olle Linder, Claes Malm, Berit Markevärn, Lars Nilsson, Jan Samuelsson, Fredrik Granath, Ola Landgren
雑誌名: J Clin Oncol. 2011 Jun 10;29(17):2410-5. doi: 10.1200/JCO.2011.34.7542. Epub 2011 May 2.
Abstract/Text PURPOSE: Patients with myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, have a propensity to develop acute myeloid leukemia (AML) and myelodysplastic syndromes (MDSs). Using population-based data from Sweden, we assessed the role of MPN treatment and subsequent AML/MDS risk with special focus on the leukemogenic potential of hydroxyurea (HU).
METHODS: On the basis of a nationwide MPN cohort (N = 11,039), we conducted a nested case-control study, including 162 patients (153 and nine with subsequent AML and MDS diagnosis, respectively) and 242 matched controls. We obtained clinical and MPN treatment data for all patients. Using logistic regression, we calculated odds ratios (ORs) as measures of AML/MDS risk.
RESULTS: Forty-one (25%) of 162 patients with MPNs with AML/MDS development were never exposed to alkylating agents, radioactive phosphorous (P(32)), or HU. Compared with patients with who were not exposed to HU, the ORs for 1 to 499 g, 500 to 999 g, more than 1,000 g of HU were 1.5 (95% CI, 0.6 to 2.4), 1.4 (95% CI, 0.6 to 3.4), and 1.3 (95% CI, 0.5 to 3.3), respectively, for AML/MDS development (not significant). Patients with MPNs who received P(32) greater than 1,000 MBq and alkylators greater than 1 g had a 4.6-fold (95% CI, 2.1 to 9.8; P = .002) and 3.4-fold (95% CI, 1.1 to 10.6; P = .015) increased risk of AML/MDS, respectively. Patients receiving two or more cytoreductive treatments had a 2.9-fold (95% CI, 1.4 to 5.9) increased risk of transformation.
CONCLUSION: The risk of AML/MDS development after MPN diagnosis was significantly associated with high exposures of P(32) and alkylators but not with HU treatment. Twenty-five percent of patients with MPNs who developed AML/MDS were not exposed to cytotoxic therapy, supporting a major role for nontreatment-related factors.

PMID 21537037  J Clin Oncol. 2011 Jun 10;29(17):2410-5. doi: 10.1200/J・・・
著者: Tiziano Barbui, Juergen Thiele, Francesco Passamonti, Elisa Rumi, Emanuela Boveri, Marco Ruggeri, Francesco Rodeghiero, Emanuele S G d'Amore, Maria Luigia Randi, Irene Bertozzi, Filippo Marino, Alessandro M Vannucchi, Elisabetta Antonioli, Valentina Carrai, Heinz Gisslinger, Veronika Buxhofer-Ausch, Leonhard Müllauer, Alessandra Carobbio, Andrea Gianatti, Naseema Gangat, Curtis A Hanson, Ayalew Tefferi
雑誌名: J Clin Oncol. 2011 Aug 10;29(23):3179-84. doi: 10.1200/JCO.2010.34.5298. Epub 2011 Jul 11.
Abstract/Text PURPOSE: The WHO diagnostic criteria underscore the role of bone marrow (BM) morphology in distinguishing essential thrombocythemia (ET) from early/prefibrotic primary myelofibrosis (PMF). This study examined the clinical relevance of such a distinction.
METHODS: Representatives from seven international centers of excellence for myeloproliferative neoplasms convened to create a clinicopathologic database of patients previously diagnosed as having ET (N = 1,104). Study eligibility criteria included availability of treatment-naive BM specimens obtained within 1 year of diagnosis. All bone marrows subsequently underwent a central re-review.
RESULTS: Diagnosis was confirmed as ET in 891 patients (81%) and was revised to early/prefibrotic PMF in 180 (16%); 33 patients were not evaluable. In early/prefibrotic PMF compared with ET, the 10-year survival rates (76% and 89%, respectively) and 15-year survival rates (59% and 80%, respectively), leukemic transformation rates at 10 years (5.8% and 0.7%, respectively) and 15 years (11.7% and 2.1%, respectively), and rates of progression to overt myelofibrosis at 10 years (12.3% and 0.8%, respectively) and 15 years (16.9% and 9.3%) were significantly worse. The respective death, leukemia, and overt myelofibrosis incidence rates per 100 patient-years for early/prefibrotic PMF compared with ET were 2.7% and 1.3% (relative risk [RR], 2.1; P < .001), 0.6% and 0.1% (RR, 5.2; P = .001), and 1% and 0.5% (RR, 2.0; P = .04). Multivariable analysis confirmed these findings and also identified age older than 60 years (hazard ratio [HR], 6.7), leukocyte count greater than 11 × 10(9)/L (HR, 2.01), anemia (HR, 2.95), and thrombosis history (HR, 2.81) as additional risk factors for survival. Thrombosis and JAK2V617F incidence rates were similar between the two groups. Survival in ET was similar to the sex- and age-standardized European population.
CONCLUSION: This study validates the clinical relevance of strict adherence to WHO criteria in the diagnosis of ET and provides important information on survival, disease complication rates, and prognostic factors in strictly WHO-defined ET and early/prefibrotic PMF.

PMID 21747083  J Clin Oncol. 2011 Aug 10;29(23):3179-84. doi: 10.1200/・・・
著者: Andreas Tiede, Jacob H Rand, Ulrich Budde, Arnold Ganser, Augusto B Federici
雑誌名: Blood. 2011 Jun 23;117(25):6777-85. doi: 10.1182/blood-2010-11-297580. Epub 2011 May 3.
Abstract/Text The acquired von Willebrand syndrome (AVWS) is a bleeding disorder that is frequently unrecognized or is misdiagnosed as von Willebrand disease. AVWS is characterized by structural or functional defects of von Willebrand factor (VWF) that are secondary to autoimmune, lymphoproliferative or myeloproliferative, malignant, cardiovascular, or other disorders. VWF abnormalities in these disorders can result from (1) antibody-mediated clearance or functional interference, (2) adsorption to surfaces of transformed cells or platelets, or (3) increased shear stress and subsequent proteolysis. Diagnosis can be challenging as no single test is usually sufficient to prove or exclude AVWS. Furthermore, there are no evidence-based guidelines for management. Treatments of the underlying medical condition, including chemo/radiotherapy, surgery, or immunosuppressants can result in remission of AVWS, but is not always feasible and successful. Because of the heterogeneous mechanisms of AVWS, more than one therapeutic approach is often required to treat acute bleeds and for prophylaxis during invasive procedures; the treatment options include, but are not limited to, desmopressin, VWF-containing concentrates, intravenous immunoglobulin, plasmapheresis or recombinant factor VIIa. Here, we review the management of AVWS with an overview on the currently available evidence and additional considerations for typical treatment situations.

PMID 21540459  Blood. 2011 Jun 23;117(25):6777-85. doi: 10.1182/blood-・・・
著者: Ayalew Tefferi, William Vainchenker
雑誌名: J Clin Oncol. 2011 Feb 10;29(5):573-82. doi: 10.1200/JCO.2010.29.8711. Epub 2011 Jan 10.
Abstract/Text To update oncologists on pathogenesis, contemporary diagnosis, risk stratification, and treatment strategies in BCR-ABL1-negative myeloproliferative neoplasms, including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Recent literature was reviewed and interpreted in the context of the authors' own experience and expertise. Pathogenetic mechanisms in PV, ET, and PMF include stem cell-derived clonal myeloproliferation and secondary stromal changes in the bone marrow and spleen. Most patients carry an activating JAK2 or MPL mutation and a smaller subset also harbors LNK, CBL, TET2, ASXL1, IDH, IKZF1, or EZH2 mutations; the precise pathogenetic contribution of these mutations is under investigation. JAK2 mutation analysis is now a formal component of diagnostic criteria for PV, ET, and PMF, but its prognostic utility is limited. Life expectancy in the majority of patients with PV or ET is near-normal and disease complications are effectively (and safely) managed by treatment with low-dose aspirin, phlebotomy, or hydroxyurea. In PMF, survival and quality of life are significantly worse and current therapy is inadequate. In ET and PV, controlled studies are needed to show added value and justify the risk of unknown long-term health effects associated with nonconventional therapeutic approaches (eg, interferon-alfa). The unmet need for treatment in PMF dictates a different approach for assessing the therapeutic value of new drugs (eg, JAK inhibitors, pomalidomide) or allogeneic stem-cell transplantation.

PMID 21220604  J Clin Oncol. 2011 Feb 10;29(5):573-82. doi: 10.1200/JC・・・
著者: Giovanni Barosi, Gunnar Birgegard, Guido Finazzi, Martin Griesshammer, Claire Harrison, Hans Carl Hasselbalch, Jean-Jacques Kiladjian, Eva Lengfelder, Mary Frances McMullin, Francesco Passamonti, John T Reilly, Alessandro M Vannucchi, Tiziano Barbui
雑誌名: Blood. 2009 May 14;113(20):4829-33. doi: 10.1182/blood-2008-09-176818. Epub 2009 Mar 10.
Abstract/Text European experts were convened to develop a definition of response to treatment in polycythemia vera (PV) and essential thrombocythemia (ET). Clinicohematologic (CH), molecular, and histologic response categories were selected. In ET, CH complete response (CR) was: platelet count less than or equal to 400 x 10(9)/L, no disease-related symptoms, normal spleen size, and white blood cell count less than or equal to 10 x 10(9)/L. Platelet count less than or equal to 600 x 10(9)/L or a decrease greater than 50% was partial response (PR). In PV, CH-CR was: hematocrit less than 45% without phlebotomy, platelet count less than or equal to 400 x 10(9)/L, white blood cell count less than or equal to 10 x 10(9)/L, and no disease-related symptoms. A hematocrit less than 45% without phlebotomy or response in 3 or more of the other criteria was defined as PR. In both ET and in PV, molecular CR was a reduction of any molecular abnormality to undetectable levels. Molecular PR was defined as a reduction more than or equal to 50% in patients with less than 50% mutant allele burden, or a reduction more than or equal to 25% in patients with more than 50% mutant allele burden. Bone marrow histologic response in ET was judged on megakaryocyte hyperplasia while on cellularity and reticulin fibrosis in PV. The combined use of these response definitions should help standardize the design and reporting of clinical studies.

PMID 19278953  Blood. 2009 May 14;113(20):4829-33. doi: 10.1182/blood-・・・
著者: Tiziano Barbui, Giovanni Barosi, Alberto Grossi, Luigi Gugliotta, Lucio N Liberato, Monia Marchetti, Maria Gabriella Mazzucconi, Francesco Rodeghiero, Sante Tura
雑誌名: Haematologica. 2004 Feb;89(2):215-32.
Abstract/Text BACKGROUND AND OBJECTIVES: The Italian Society of Hematology (SIE) and the two affiliated Societies (SIES and GITMO) commissioned a project to develop guidelines for the therapy of essential thrombocythemia (ET) using evidence-based knowledge and consensus formation techniques.
DESIGN AND METHODS: Key questions on the optimal management of ET patients were formulated by an Advisory Council (AC) and approved by an Expert Panel (EP) composed of 7 senior hematologists. The AC systematically reviewed the published literature from 1980 to August 2002, and articles were graded according to their internal validity and quality. Using the Delphi technique, the EP was asked to answer the key questions according to the available evidence. From September 2002 to March 2003, four Consensus Conferences were held in accordance with the Nominal Group Technique with the goal of solving residual disagreement on recommendations.
RESULTS: The EP provided recommendations on when to start platelet-lowering therapy, the most appropriate platelet-lowering agent, the use of anti-platelet therapy, and the management of women in childbearing age and of pregnant women.
INTERPRETATION AND CONCLUSIONS: By using evidence and consensus, recommendations for the treatment of key problems in ET have been issued. Statements are graded according to the strength of the supporting evidence and uncertainty is explicitly declared.

PMID 15003898  Haematologica. 2004 Feb;89(2):215-32.
著者: Claire N Harrison, Peter J Campbell, Georgina Buck, Keith Wheatley, Clare L East, David Bareford, Bridget S Wilkins, Jon D van der Walt, John T Reilly, Andrew P Grigg, Paul Revell, Barrie E Woodcock, Anthony R Green, United Kingdom Medical Research Council Primary Thrombocythemia 1 Study
雑誌名: N Engl J Med. 2005 Jul 7;353(1):33-45. doi: 10.1056/NEJMoa043800.
Abstract/Text BACKGROUND: We conducted a randomized comparison of hydroxyurea with anagrelide in the treatment of essential thrombocythemia.
METHODS: A total of 809 patients with essential thrombocythemia who were at high risk for vascular events received low-dose aspirin plus either anagrelide or hydroxyurea. The composite primary end point was the actuarial risk of arterial thrombosis (myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic attack, or peripheral arterial thrombosis), venous thrombosis (deep-vein thrombosis, splanchnic-vein thrombosis, or pulmonary embolism), serious hemorrhage, or death from thrombotic or hemorrhagic causes.
RESULTS: After a median follow-up of 39 months, patients in the anagrelide group were significantly more likely than those in the hydroxyurea group to have reached the primary end point (odds ratio, 1.57; 95 percent confidence interval, 1.04 to 2.37; P=0.03). As compared with hydroxyurea plus aspirin, anagrelide plus aspirin was associated with increased rates of arterial thrombosis (P=0.004), serious hemorrhage (P=0.008), and transformation to myelofibrosis (P=0.01) but with a decreased rate of venous thromboembolism (P=0.006). Patients receiving anagrelide were more likely to withdraw from their assigned treatment (P<0.001). Equivalent long-term control of the platelet count was achieved in both groups.
CONCLUSIONS: Hydroxyurea plus low-dose aspirin is superior to anagrelide plus low-dose aspirin for patients with essential thrombocythemia at high risk for vascular events.

Copyright 2005 Massachusetts Medical Society.
PMID 16000354  N Engl J Med. 2005 Jul 7;353(1):33-45. doi: 10.1056/NEJ・・・
著者: S Cortelazzo, G Finazzi, M Ruggeri, O Vestri, M Galli, F Rodeghiero, T Barbui
雑誌名: N Engl J Med. 1995 Apr 27;332(17):1132-6. doi: 10.1056/NEJM199504273321704.
Abstract/Text BACKGROUND: Abnormalities in the number and function of platelets may contribute to thromboembolic complications in patients with essential thrombocythemia. We assessed whether maintaining the platelet count below 600,000 per cubic millimeter with hydroxyurea reduces the incidence of thrombosis in patients with essential thrombocythemia and a high risk of thrombosis.
METHODS: A total of 114 patients with essential thrombocythemia (77 women and 37 men; median age, 68 years; range, 40 to 85) and a median platelet count of 788,000 per cubic millimeter (range, 533,000 to 1,240,000 per cubic millimeter) were randomly assigned to receive hydroxyurea (56 patients) or no myelosuppressive therapy (58 patients). Ninety-seven (85 percent) were over 60 years old, and 52 (46 percent) had had thrombosis. The two groups were matched for age, sex, and platelet count at randomization. Antiplatelet prophylaxis with aspirin or ticlopidine was not stopped. Follow-up lasted a median of 27 months in both groups.
RESULTS: Two patients (3.6 percent) treated with hydroxyurea had thrombotic episodes (one stroke and one myocardial infarction), whereas 14 patients (24 percent) in the control group had thrombotic episodes (one stroke, five transient ischemic attacks, five peripheral arterial occlusions, one deep-vein thrombosis, and two cases of superficial thrombophlebitis). The difference (20.4 percentage points; 95 percent confidence interval, 8.5 to 32 percent) was statistically significant (chi-square with Yates' correction, 8.3; 1 df; P = 0.003).
CONCLUSIONS: Hydroxyurea is effective in preventing thrombosis in high-risk patients with essential thrombocythemia.

PMID 7700286  N Engl J Med. 1995 Apr 27;332(17):1132-6. doi: 10.1056/・・・
著者: Peter J Campbell, Linda M Scott, Georgina Buck, Keith Wheatley, Clare L East, Joanne T Marsden, Audrey Duffy, Elaine M Boyd, Anthony J Bench, Mike A Scott, George S Vassiliou, Donald W Milligan, Steve R Smith, Wendy N Erber, David Bareford, Bridget S Wilkins, John T Reilly, Claire N Harrison, Anthony R Green, United Kingdom Myeloproliferative Disorders Study Group, Medical Research Council Adult Leukaemia Working Party, Australasian Leukaemia and Lymphoma Group
雑誌名: Lancet. 2005 Dec 3;366(9501):1945-53. doi: 10.1016/S0140-6736(05)67785-9.
Abstract/Text BACKGROUND: An acquired V617F mutation in JAK2 occurs in most patients with polycythaemia vera, but is seen in only half those with essential thrombocythaemia and idiopathic myelofibrosis. We aimed to assess whether patients with the mutation are biologically distinct from those without, and why the same mutation is associated with different disease phenotypes.
METHODS: Two sensitive PCR-based methods were used to assess the JAK2 mutation status of 806 patients with essential thrombocythaemia, including 776 from the Medical Research Council's Primary Thrombocythaemia trial (MRC PT-1) and two other prospective studies. Laboratory and clinical features, response to treatment, and clinical events were compared for V617F-positive and V617F-negative patients with essential thrombocythaemia.
FINDINGS: Mutation-positive patients had multiple features resembling polycythaemia vera, with significantly increased haemoglobin (mean increase 9.6 g/L, 95% CI 7.6-11.6 g/L; p<0.0001), neutrophil counts (1.1x10(9)/L, 0.7-1.5x10(9)/L; p<0.0001), bone marrow erythropoiesis and granulopoiesis, more venous thromboses, and a higher rate of polycythaemic transformation than those without the mutation. Mutation-positive patients had lower serum erythropoietin (mean decrease 13.8 U/L; 95% CI, 10.8-16.9 U/L; p<0.0001) and ferritin (n=182; median 58 vs 91 mug/L; p=0.01) concentrations than did mutation-negative patients. Mutation-negative patients did, nonetheless, show many clinical and laboratory features that were characteristic of a myeloproliferative disorder. V617F-positive individuals were more sensitive to therapy with hydroxyurea, but not anagrelide, than those without the JAK2 mutation.
INTERPRETATION: Our results suggest that JAK2 V617F-positive essential thrombocythaemia and polycythaemia vera form a biological continuum, with the degree of erythrocytosis determined by physiological or genetic modifiers.

PMID 16325696  Lancet. 2005 Dec 3;366(9501):1945-53. doi: 10.1016/S014・・・
著者: Alberto Alvarez-Larrán, Arturo Pereira, Eduardo Arellano-Rodrigo, Juan-Carlos Hernández-Boluda, Francisco Cervantes, Carlos Besses
雑誌名: Br J Haematol. 2013 Jun;161(6):865-71. doi: 10.1111/bjh.12321. Epub 2013 Apr 12.
Abstract/Text The effectiveness of low-dose aspirin in the primary prevention of thrombosis in patients with high-risk essential thrombocythaemia (ET) treated with cytoreductive drugs is not well established. The risk-benefit balance of low-dose aspirin plus cytoreductive therapy compared with cytoreduction alone was retrospectively analysed in 247 patients with high-risk ET without prior thrombosis. Follow-up was 763 and 685 person-years for cytoreduction plus low-dose aspirin and cytoreduction alone, respectively. The rate of thrombosis was not significantly reduced in patients on cytoreduction plus aspirin (14·4 events per 1000 person-years) when compared with those on cytoreduction alone (24·8 events per 1000 person-years; P = 0·2). However, in the subgroup of patients older than 60 years, the addition of low-dose aspirin was associated with a significantly lower rate of thrombosis (8·6 vs. 29·2 thrombosis per 1000 person-years for combined treatment and cytoreduction alone, respectively, P = 0·02). The rate of major bleeding was significantly higher with combined therapy than with cytoreduction alone both in the whole series (14·4 vs. 1·4 haemorrhagic events per 1000 person-years, respectively, P = 0·006) and in the subgroup of patients older than 60 years. In conclusion, low-dose aspirin benefits high-risk ET patients older than 60 years receiving cytoreductive therapy as primary prophylaxis of thrombosis.

© 2013 John Wiley & Sons Ltd.
PMID 23577924  Br J Haematol. 2013 Jun;161(6):865-71. doi: 10.1111/bjh・・・
著者: Heinz Gisslinger, Mirjana Gotic, Jerzy Holowiecki, Miroslav Penka, Juergen Thiele, Hans-Michael Kvasnicka, Robert Kralovics, Petro E Petrides, ANAHYDRET Study Group
雑誌名: Blood. 2013 Mar 7;121(10):1720-8. doi: 10.1182/blood-2012-07-443770. Epub 2013 Jan 11.
Abstract/Text High platelet counts in essential thrombocythemia (ET) can be effectively lowered by treatment with either anagrelide or hydroxyurea. In 259 previously untreated, high-risk patients with ET, diagnosed according to the World Health Organization classification system, the efficacy and tolerability of anagrelide compared with hydroxyurea were investigated in a prospective randomized noninferiority phase 3 study in an a priori-ordered hypothesis. Confirmatory proof of the noninferiority of anagrelide was achieved after 6 months using the primary end point criteria and was further confirmed after an observation time of 12 and 36 months for platelet counts, hemoglobin levels, leukocyte counts (P < .001), and ET-related events (HR, 1.19 [95% CI, 0.61-2.30], 1.03 [95% CI, 0.57-1.81], and 0.92 [95% CI, 0.57-1.46], respectively). During the total observation time of 730 patient-years, there was no significant difference between the anagrelide and hydroxyurea group regarding incidences of major arterial (7 vs 8) and venous (2 vs 6) thrombosis, severe bleeding events (5 vs 2), minor arterial (24 vs 20) and venous (3 vs 3) thrombosis and minor bleeding events (18 vs 15), or rates of discontinuation (adverse events 12 vs 15 or lack of response 5 vs 2). Disease transformation into myelofibrosis or secondary leukemia was not reported. Anagrelide as a selective platelet-lowering agent is not inferior compared with hydroxyurea in the prevention of thrombotic complications in patients with ET diagnosed according to the World Health Organization system. This trial was registered at http://www.clinicaltrials.gov as #NCT01065038.

PMID 23315161  Blood. 2013 Mar 7;121(10):1720-8. doi: 10.1182/blood-20・・・
著者: Yuzuru Kanakura, Yoshitaka Miyakawa, Paul Wilde, Jonathan Smith, Heinrich Achenbach, Shinichiro Okamoto
雑誌名: Int J Hematol. 2014 Oct;100(4):353-60. doi: 10.1007/s12185-014-1631-x. Epub 2014 Aug 27.
Abstract/Text Essential thrombocythemia (ET) is usually managed by anti-platelet therapy. European guidelines recommend that patients with ET at high risk of developing thrombohemorrhagic events should be placed on cytoreductive therapy (CRT). In Japan, hydroxycarbamide (HC) is the most widely used CRT; however, treatment options for patients who become intolerant or refractory to initial treatment are limited. This study sought to determine the efficacy, safety, and tolerability of anagrelide in high-risk Japanese adults with ET who were intolerant or refractory to their first-line CRT. Fifty-three patients were enrolled in the study. Of those, 67.9 % had a platelet response (<60 × 10(4)/µL) and 45.3 % achieved normalization of platelet counts (≤40 × 10(4)/µL) on anagrelide therapy. The median time to platelet count response was 98.5 days and the median time to platelet count normalization was 274.0 days. The median daily dose administered was 1.9 mg/day. The most common adverse events observed during anagrelide treatment were anemia, headache, palpitations, and diarrhea. The majority of these were either mild or moderate in severity. Overall, the safety profile of anagrelide in high-risk Japanese patients with ET was consistent with the European Summary of Product Characteristics.

PMID 25160063  Int J Hematol. 2014 Oct;100(4):353-60. doi: 10.1007/s12・・・
著者: Anna L Godfrey, Peter J Campbell, Cathy MacLean, Georgina Buck, Julia Cook, Julie Temple, Bridget S Wilkins, Keith Wheatley, Jyoti Nangalia, Jacob Grinfeld, Mary Frances McMullin, Cecily Forsyth, Jean-Jacques Kiladjian, Anthony R Green, Claire N Harrison, United Kingdom Medical Research Council Primary Thrombocythemia-1 Study, United Kingdom National Cancer Research Institute Myeloproliferative Neoplasms Subgroup, French Intergroup of Myeloproliferative Neoplasms, and the Australasian Leukaemia and Lymphoma Group.
雑誌名: J Clin Oncol. 2018 Aug 28;:JCO2018788414. doi: 10.1200/JCO.2018.78.8414. Epub 2018 Aug 28.
Abstract/Text Purpose Cytoreductive therapy is beneficial in patients with essential thrombocythemia (ET) at high risk of thrombosis. However, its value in those lacking high-risk features remains unknown. This open-label, randomized trial compared hydroxycarbamide plus aspirin with aspirin alone in patients with ET age 40 to 59 years and without high-risk factors or extreme thrombocytosis. Patients and Methods Patients were age 40 to 59 years and lacked a history of ischemia, thrombosis, embolism, hemorrhage, extreme thrombocytosis (platelet count ≥ 1,500 × 109/L), hypertension, or diabetes requiring therapy. In all, 382 patients were randomly assigned 1:1 to hydroxycarbamide plus aspirin or aspirin alone. The composite primary end point was time to arterial or venous thrombosis, serious hemorrhage, or death from vascular causes. Secondary end points were time to first arterial or venous thrombosis, first serious hemorrhage, death, incidence of transformation, and patient-reported quality of life. Results After a median follow-up of 73 months and a total follow-up of 2,373 patient-years, there was no significant difference between the arms in the likelihood of patients reaching the primary end point (hazard ratio, 0.98; 95% CI, 0.42 to 2.25; P = 1.0). The incidence of significant vascular events was low, at 0.93 per 100 patient-years (95% CI, 0.61 to 1.41). There were also no differences in overall survival; in the composite end point of transformation to myelofibrosis, acute myeloid leukemia, or myelodysplasia; in adverse events; or in patient-reported quality of life. Conclusion In patients with ET age 40 to 59 years and lacking high-risk factors for thrombosis or extreme thrombocytosis, preemptive addition of hydroxycarbamide to aspirin did not reduce vascular events, myelofibrotic transformation, or leukemic transformation. Patients age 40 to 59 years without other clinical indications for treatment (such as previous thrombosis or hemorrhage) who have a platelet count < 1,500 × 109/L should not receive cytoreductive therapy.

PMID 30153096  J Clin Oncol. 2018 Aug 28;:JCO2018788414. doi: 10.1200/・・・
著者: Alfonso Quintás-Cardama, Hagop Kantarjian, Taghi Manshouri, Rajyalakshmi Luthra, Zeev Estrov, Sherry Pierce, Mary Ann Richie, Gautam Borthakur, Marina Konopleva, Jorge Cortes, Srdan Verstovsek
雑誌名: J Clin Oncol. 2009 Nov 10;27(32):5418-24. doi: 10.1200/JCO.2009.23.6075. Epub 2009 Oct 13.
Abstract/Text PURPOSE: We conducted a phase II study of pegylated interferon alfa-2a (PEG-IFN-alpha-2a) in patients with essential thrombocythemia (ET) and polycythemia vera (PV).
PATIENTS AND METHODS: Seventy-nine patients (40 with PV and 39 with ET) have been treated. Median time from diagnosis to PEG-IFN-alpha-2a was 54 months in patients with PV and 33 months in patients with ET. Eighty-one percent of patients had received prior therapy. The first three patients received PEG-IFN-alpha-2a at 450 microg weekly. As a result of poor tolerance, this dose was decreased in a stepwise manner to a current starting dose of 90 microg weekly. Seventy-seven patients are evaluable and have been observed for a median of 21 months.
RESULTS: The overall hematologic response rate was 80% in PV and 81% in ET (complete in 70% and 76% of patients, respectively). The JAK2(V617F) mutation was detected in 18 patients with ET and 38 patients with PV; sequential measurements by a pyrosequencing assay were available in 16 patients with ET and 35 patients with PV. The molecular response rate was 38% in ET and 54% in PV, being complete (undetectable JAK2(V617F)) in 6% and 14%, respectively. The JAK2(V617F) mutant allele burden continued to decrease with no clear evidence for a plateau. The tolerability of PEG-IFN-alpha-2a at 90 microg weekly was excellent.
CONCLUSION: PEG-IFN-alpha-2a resulted in remarkable clinical activity, high rates of molecular response, and acceptable toxicity in patients with advanced ET or PV. The ability of PEG-IFN-alpha-2a to induce complete molecular responses suggests selective targeting of the malignant clone.

PMID 19826111  J Clin Oncol. 2009 Nov 10;27(32):5418-24. doi: 10.1200/・・・

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契約期間が通常12ヵ月のところ、14ヵ月ご利用いただけます。

優待コード: (利用期限:まで)

ご契約はこちらから