Browse > Article
http://dx.doi.org/10.3904/kjim.2015.30.6.771

Guidelines for the management of myeloproliferative neoplasms  

Choi, Chul Won (Division of Oncology-Hematology, Department of Internal Medicine, Korea University Guro Hospital)
Bang, Soo-Mee (Department of Internal Medicine, Seoul National University Bundang Hospital)
Jang, Seongsoo (Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine)
Jung, Chul Won (Division of Hematology/Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine)
Kim, Hee-Jin (Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine)
Kim, Ho Young (Department of Internal Medicine, Hallym University Sacred Heart Hospital)
Kim, Soo-Jeong (Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine)
Kim, Yeo-Kyeoung (Division of Hematology-Oncology, Department of Internal Medicine, Chonnam National University Hwasun Hospital)
Park, Jinny (Division of Hematology-Oncology, Department of Internal Medicine, Gachon University Gil Medical Center)
Won, Jong-Ho (Division of Hematology-Oncology, Department of Internal Medicine, Soonchunhyang University College of Medicine)
Publication Information
The Korean journal of internal medicine / v.30, no.6, 2015 , pp. 771-788 More about this Journal
Abstract
Polycythemia vera, essential thrombocythemia, and primary myelofibrosis are collectively known as 'Philadelphia-negative classical myeloproliferative neoplasms (MPNs).' The discovery of new genetic aberrations such as Janus kinase 2 (JAK2) have enhanced our understanding of the pathophysiology of MPNs. Currently, the $JAK_2$ mutation is not only a standard criterion for diagnosis but is also a new target for drug development. The $JAK_{1/2}$ inhibitor, ruxolitinib, was the first JAK inhibitor approved for patients with intermediate- to high-risk myelofibrosis and its effects in improving symptoms and survival benefits were demonstrated by randomized controlled trials. In 2011, the Korean Society of Hematology MPN Working Party devised diagnostic and therapeutic guidelines for Korean MPN patients. Subsequently, other genetic mutations have been discovered and many kinds of new drugs are now under clinical investigation. In view of recent developments, we have revised the guidelines for the diagnosis and management of MPN based on published evidence and the experiences of the expert panel. Here we describe the epidemiology, new genetic mutations, and novel therapeutic options as well as diagnostic criteria and standard treatment strategies for MPN patients in Korea.
Keywords
Polycythemia vera; Thrombocythemia, essential; Primary myelofibrosis; Practice guideline;
Citations & Related Records
Times Cited By KSCI : 3  (Citation Analysis)
연도 인용수 순위
1 Tefferi A, Vardiman JW. Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia 2008;22:14-22.   DOI
2 Barbui T, Barosi G, Birgegard G, et al. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet. J Clin Oncol 2011;29:761-770.   DOI
3 Bang SM, Kim HY, Kim HJ, et al. Diagnostic and therapeutic guideline for myeloproliferative neoplasm. J Korean Med Assoc 2011;54:112-126.   DOI
4 Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon: International Agency for Research on Cancer, 2008.
5 Klampfl T, Gisslinger H, Harutyunyan AS, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med 2013;369:2379-2390.   DOI
6 Nangalia J, Massie CE, Baxter EJ, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med 2013;369:2391-2405.   DOI
7 Alvarez-Larran A, Ancochea A, Garcia M, et al. WHO-histological criteria for myeloproliferative neoplasms: reproducibility, diagnostic accuracy and correlation with gene mutations and clinical outcomes. Br J Haematol 2014;166:911-919.   DOI
8 Austin SK, Lambert JR. The JAK2 V617F mutation and thrombosis. Br J Haematol 2008;143:307-320.   DOI
9 Sarid N, Eshel R, Rahamim E, et al. JAK2 mutation: an aid in the diagnosis of occult myeloproliferative neoplasms in patients with major intraabdominal vein thrombosis and normal blood counts. Isr Med Assoc J 2013;15:698-700.
10 Barbui T, Thiele J, Vannucchi AM, Tefferi A. Rethinking the diagnostic criteria of polycythemia vera. Leukemia 2014;28:1191-1195.   DOI
11 Di Nisio M, Barbui T, Di Gennaro L, et al. The haematocrit and platelet target in polycythemia vera. Br J Haematol 2007;136:249-259.   DOI
12 Moliterno AR, Williams DM, Rogers O, Spivak JL. Molecular mimicry in the chronic myeloproliferative disorders: reciprocity between quantitative JAK2 V617F and Mpl expression. Blood 2006;108:3913-3915.   DOI
13 Wilkins BS, Erber WN, Bareford D, et al. Bone marrow pathology in essential thrombocythemia: interobserver reliability and utility for identifying disease subtypes. Blood 2008;111:60-70.   DOI
14 Harrison CN, Butt N, Campbell P, et al. Modification of British Committee for Standards in Haematology diagnostic criteria for essential thrombocythaemia. Br J Haematol 2014;167:421-423.   DOI
15 Kiladjian JJ. The spectrum of JAK2-positive myeloproliferative neoplasms. Hematology Am Soc Hematol Educ Program 2012;2012:561-566.
16 Vannucchi AM, Antonioli E, Guglielmelli P, et al. Prospective identification of high-risk polycythemia vera patients based on JAK2(V617F) allele burden. Leukemia 2007;21:1952-1959.   DOI
17 Scott LM, Tong W, Levine RL, et al. JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med 2007;356:459-468.   DOI
18 Scott LM. The JAK2 exon 12 mutations: a comprehensive review. Am J Hematol 2011;86:668-676.   DOI
19 Kim HJ, Jang JH, Yoo EH, et al. JAK2 V617F and MPL W515L/K mutations in Korean patients with essential thrombocythemia. Korean J Lab Med 2010;30:474-476.   DOI
20 Ha JS, Kim YK. Calreticulin exon 9 mutations in myeloproliferative neoplasms. Ann Lab Med 2015;35:22-27.   DOI
21 Jang JH, Seo JY, Jang J, et al. Hereditary gene mutations in Korean patients with isolated erythrocytosis. Ann Hematol 2014;93:931-935.   DOI
22 Rumi E, Pietra D, Ferretti V, et al. JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes. Blood 2014;123:1544-1551.   DOI
23 Lindsley RC, Ebert BL. The biology and clinical impact of genetic lesions in myeloid malignancies. Blood 2013;122:3741-3748.   DOI
24 Patnaik MM, Tefferi A. The complete evaluation of erythrocytosis: congenital and acquired. Leukemia 2009;23:834-844.   DOI
25 Ho CL, Lasho TL, Butterfield JH, Tefferi A. Global cytokine analysis in myeloproliferative disorders. Leuk Res 2007;31:1389-1392.   DOI
26 Martyre MC, Magdelenat H, Bryckaert MC, Laine-Bidron C, Calvo F. Increased intraplatelet levels of platelet-derived growth factor and transforming growth factor-beta in patients with myelofibrosis with myeloid metaplasia. Br J Haematol 1991;77:80-86.   DOI
27 Di Raimondo F, Azzaro MP, Palumbo GA, et al. Elevated vascular endothelial growth factor (VEGF) serum levels in idiopathic myelofibrosis. Leukemia 2001;15:976-980.   DOI
28 Panteli KE, Hatzimichael EC, Bouranta PK, et al. Serum interleukin (IL)-1, IL-2, sIL-2Ra, IL-6 and thrombopoietin levels in patients with chronic myeloproliferative diseases. Br J Haematol 2005;130:709-715.   DOI
29 Mesa RA, Niblack J, Wadleigh M, et al. The burden of fatigue and quality of life in myeloproliferative disorders (MPDs): an international Internet-based survey of 1179 MPD patients. Cancer 2007;109:68-76.   DOI
30 Mesa RA, Schwager S, Radia D, et al. The Myelofibrosis Symptom Assessment Form (MFSAF): an evidence-based brief inventory to measure quality of life and symptomatic response to treatment in myelofibrosis. Leuk Res 2009;33:1199-1203.   DOI
31 Cervantes F, Dupriez B, Pereira A, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood 2009;113:2895-2901.   DOI
32 Passamonti F, Cervantes F, Vannucchi AM, et al. Dynamic International Prognostic Scoring System (DIPSS) predicts progression to acute myeloid leukemia in primary myelofibrosis. Blood 2010;116:2857-2858.   DOI
33 Gangat N, Caramazza D, Vaidya R, et al. DIPSS plus: a refined Dynamic International Prognostic Scoring System for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status. J Clin Oncol 2011;29:392-397.   DOI
34 Vannucchi AM, Lasho TL, Guglielmelli P, et al. Mutations and prognosis in primary myelofibrosis. Leukemia 2013;27:1861-1869.   DOI
35 Guglielmelli P, Lasho TL, Rotunno G, et al. The number of prognostically detrimental mutations and prognosis in primary myelofibrosis: an international study of 797 patients. Leukemia 2014;28:1804-1810.   DOI
36 Guglielmelli P, Barosi G, Pieri L, Antonioli E, Bosi A, Vannucchi AM. JAK2V617F mutational status and allele burden have little influence on clinical phenotype and prognosis in patients with post-polycythemia vera and post-essential thrombocythemia myelofibrosis. Haematologica 2009;94:144-146.   DOI
37 Emanuel RM, Dueck AC, Geyer HL, et al. Myeloproliferative neoplasm (MPN) symptom assessment form total symptom score: prospective international assessment of an abbreviated symptom burden scoring system among patients with MPNs. J Clin Oncol 2012;30:4098-4103.   DOI
38 Pardanani A, Guglielmelli P, Lasho TL, et al. Primary myelofibrosis with or without mutant MPL: comparison of survival and clinical features involving 603 patients. Leukemia 2011;25:1834-1839.   DOI
39 Tefferi A, Vaidya R, Caramazza D, Finke C, Lasho T, Pardanani A. Circulating interleukin (IL)-8, IL-2R, IL-12, and IL-15 levels are independently prognostic in primary myelofibrosis: a comprehensive cytokine profiling study. J Clin Oncol 2011;29:1356-1363.   DOI
40 Tefferi A, Cervantes F, Mesa R, et al. Revised response criteria for myelofibrosis: International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus report. Blood 2013;122:1395-1398.   DOI
41 Mendoza TR, Wang XS, Cleeland CS, et al. The rapid assessment of fatigue severity in cancer patients: use of the Brief Fatigue Inventory. Cancer 1999;85:1186-1196.   DOI
42 Scherber R, Dueck AC, Johansson P, et al. The Myeloproliferative Neoplasm Symptom Assessment Form (MPNSAF): international prospective validation and reliability trial in 402 patients. Blood 2011;118:401-408.   DOI
43 Tefferi A, Hudgens S, Mesa R, et al. Use of the functional assessment of cancer therapy: anemia in persons with myeloproliferative neoplasm-associated myelofibrosis and anemia. Clin Ther 2014;36:560-566.   DOI
44 Girodon F, Schaeffer C, Cleyrat C, et al. Frequent reduction or absence of detection of the JAK2-mutated clone in JAK2V617F-positive patients within the first years of hydroxyurea therapy. Haematologica 2008;93:1723-1727.   DOI
45 Abdel-Wahab OI, Levine RL. Primary myelofibrosis: update on definition, pathogenesis, and treatment. Annu Rev Med 2009;60:233-245.   DOI
46 Thiele J, Kvasnicka HM, Facchetti F, Franco V, van der Walt J, Orazi A. European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica 2005;90:1128-1132.
47 Andersen CL, Andreasson B, Hasselbalch H, et al. Nordic guidelines on the diagnosis and treatment of patients with myeloproliferative neoplasms [Internet]. Copenhagen (DK): Nordic MPN Study Group, 2013 [cited 2015 Aug 17]. Available from: http://www.nmpn.org/index.php/guidelines/1-nmpn-guidelines-2013/file.
48 Vannucchi AM, Pieri L, Guglielmelli P. JAK2 allele burden in the myeloproliferative neoplasms: effects on phenotype, prognosis and change with treatment. Ther Adv Hematol 2011;2:21-32.   DOI
49 Lange T, Edelmann A, Siebolts U, et al. JAK2 p.V617F allele burden in myeloproliferative neoplasms one month after allogeneic stem cell transplantation significantly predicts outcome and risk of relapse. Haematologica 2013;98:722-728.   DOI
50 Ballen KK, Shrestha S, Sobocinski KA, et al. Outcome of transplantation for myelofibrosis. Biol Blood Marrow Transplant 2010;16:358-367.   DOI
51 Gupta V, Hari P, Hoffman R. Allogeneic hematopoietic cell transplantation for myelofibrosis in the era of JAK inhibitors. Blood 2012;120:1367-1379.   DOI
52 Abelsson J, Merup M, Birgegard G, et al. The outcome of allo-HSCT for 92 patients with myelofibrosis in the Nordic countries. Bone Marrow Transplant 2012;47:380-386.   DOI
53 McLornan DP, Mead AJ, Jackson G, Harrison CN. Allogeneic stem cell transplantation for myelofibrosis in 2012. Br J Haematol 2012;157:413-425.   DOI
54 Reilly JT, McMullin MF, Beer PA, et al. Guideline for the diagnosis and management of myelofibrosis. Br J Haematol 2012;158:453-471.   DOI
55 Tefferi A. Primary myelofibrosis: 2013 update on diagnosis, risk-stratification, and management. Am J Hematol 2013;88:141-150.   DOI
56 Fruehauf S, Buss EC, Tropaly J, Kreipe HH, Ho AD. Myeloablative conditioning in myelofibrosis using i.v. treosulfan and autologous peripheral blood progenitor cell transplantation with high doses of CD34+ cells results in hematologic responses: a follow-up of three patients. Haematologica 2005;90:ECR08.
57 Huang J, Tefferi A. Erythropoiesis stimulating agents have limited therapeutic activity in transfusion-dependent patients with primary myelofibrosis regardless of serum erythropoietin level. Eur J Haematol 2009;83:154-155.   DOI
58 Tefferi A. Primary myelofibrosis: 2012 update on diagnosis, risk stratification, and management. Am J Hematol 2011;86:1017-1026.   DOI
59 Cervantes F, Alvarez-Larran A, Domingo A, Arellano-Rodrigo E, Montserrat E. Efficacy and tolerability of danazol as a treatment for the anaemia of myelofibrosis with myeloid metaplasia: long-term results in 30 patients. Br J Haematol 2005;129:771-775.   DOI
60 Mesa RA, Steensma DP, Pardanani A, et al. A phase 2 trial of combination low-dose thalidomide and prednisone for the treatment of myelofibrosis with myeloid metaplasia. Blood 2003;101:2534-2541.   DOI
61 Mesa RA, Yao X, Cripe LD, et al. Lenalidomide and prednisone for myelofibrosis: Eastern Cooperative Oncology Group (ECOG) phase 2 trial E4903. Blood 2010;116:4436-4438.   DOI
62 Mesa RA. The evolving treatment paradigm in myelofibrosis. Leuk Lymphoma 2013;54:242-251.   DOI
63 Martinez-Trillos A, Gaya A, Maffioli M, et al. Efficacy and tolerability of hydroxyurea in the treatment of the hyperproliferative manifestations of myelofibrosis: results in 40 patients. Ann Hematol 2010;89:1233-1237.   DOI
64 Odenike O, Tefferi A. Conventional and new treatment options for myelofibrosis with myeloid metaplasia. Semin Oncol 2005;32:422-431.   DOI
65 Hasselbalch HC, Kiladjian JJ, Silver RT. Interferon alfa in the treatment of Philadelphia-negative chronic myeloproliferative neoplasms. J Clin Oncol 2011;29:e564-e565.   DOI
66 Ianotto JC, Boyer-Perrard F, Gyan E, et al. Efficacy and safety of pegylated-interferon ${\alpha}$-2a in myelofibrosis: a study by the FIM and GEM French cooperative groups. Br J Haematol 2013;162:783-791.   DOI
67 Mesa RA. How I treat symptomatic splenomegaly in patients with myelofibrosis. Blood 2009;113:5394-5400.   DOI
68 Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo- controlled trial of ruxolitinib for myelofibrosis. N Engl J Med 2012;366:799-807.   DOI
69 Cervantes F, Vannucchi AM, Kiladjian JJ, et al. Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. Blood 2013;122:4047-4053.   DOI
70 Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med 2012;366:787-798.   DOI
71 Pardanani A, Tefferi A, Jamieson C, et al. Long-term follow up of a randomized phase II study of the JAK2-selective inhibitor fedratinib (SAR302503) in patients with myelofibrosis (MF). Blood 2013;122(21):4047.   DOI
72 Komrokji RS, Wadleigh M, Seymour JF, et al. Results of a phase 2 study of pacritinib (SB1518), a novel oral JAK2 inhibitor, in patients with primary, post-polycythemia vera, and post-essential thrombocythemia myelofibrosis. Blood 2011;118(21):130-131.
73 Pardanani A, Laborde RR, Lasho TL, et al. Safety and efficacy of CYT387, a JAK1 and JAK2 inhibitor, in myelofibrosis. Leukemia 2013;27:1322-1327.   DOI
74 Crisa E, Venturino E, Passera R, et al. A retrospective study on 226 polycythemia vera patients: impact of median hematocrit value on clinical outcomes and survival improvement with anti-thrombotic prophylaxis and non-alkylating drugs. Ann Hematol 2010;89:691-699.   DOI
75 Passamonti F, Rumi E, Pietra D, 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;24:1574-1579.   DOI
76 Marchioli R, Finazzi G, Landolfi R, et al. Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. J Clin Oncol 2005;23:2224-2232.   DOI
77 Hensley B, Geyer H, Mesa R. Polycythemia vera: current pharmacotherapy and future directions. Expert Opin Pharmacother 2013;14:609-617.   DOI
78 Cervantes F, Passamonti F, Barosi G. Life expectancy and prognostic factors in the classic BCR/ABL-negative myeloproliferative disorders. Leukemia 2008;22:905-914.   DOI
79 Barosi G, Birgegard G, Finazzi G, et al. Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference. Blood 2009;113:4829-4833.   DOI
80 Barbui T, Finazzi MC, Finazzi G. Front-line therapy in polycythemia vera and essential thrombocythemia. Blood Rev 2012;26:205-211.   DOI
81 Marchioli R, Finazzi G, Specchia G, et al. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med 2013;368:22-33.   DOI
82 Landolfi R, Marchioli R, Kutti J, et al. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med 2004;350:114-124.   DOI
83 Silver RT. Long-term effects of the treatment of polycythemia vera with recombinant interferon-alpha. Cancer 2006;107:451-458.   DOI
84 Steven HS, Swerdlow EC, Harris NL, Mature T- and NKcell neoplasms. In: Swerdlow SH, Campo E, Harris NL, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon: International Agency for Research on Cancer, 2008:269-320.
85 Tiede A, Rand JH, Budde U, Ganser A, Federici AB. How I treat the acquired von Willebrand syndrome. Blood 2011;117:6777-6785.   DOI
86 Cortelazzo S, Finazzi G, Ruggeri M, et al. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med 1995;332:1132-1136.   DOI
87 Barosi G, Mesa R, Finazzi G, et al. Revised response criteria for polycythemia vera and essential thrombocythemia: an ELN and IWG-MRT consensus project. Blood 2013;121:4778-4781.   DOI
88 Ruggeri M, Finazzi G, Tosetto A, Riva S, Rodeghiero F, Barbui T. No treatment for low-risk thrombocythaemia: results from a prospective study. Br J Haematol 1998;103:772-777.   DOI
89 Tefferi A, Gangat N, Wolanskyj AP. Management of extreme thrombocytosis in otherwise low-risk essential thrombocythemia; does number matter? Blood 2006;108:2493-2494.   DOI
90 Finazzi G, Ruggeri M, Rodeghiero F, Barbui T. Second malignancies in patients with essential thrombocythaemia treated with busulphan and hydroxyurea: long-term follow-up of a randomized clinical trial. Br J Haematol 2000;110:577-583.   DOI
91 Harrison CN, Campbell PJ, Buck G, et al. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med 2005;353:33-45.   DOI
92 Watson KV, Key N. Vascular complications of essential thrombocythaemia: a link to cardiovascular risk factors. Br J Haematol 1993;83:198-203.   DOI
93 Pernerstorfer T, Stohlawetz P, Stummvoll G, et al. Lowdose aspirin does not lower in vivo platelet activation in healthy smokers. Br J Haematol 1998;102:1229-1231.   DOI
94 Martinelli P, Martinelli V, Agangi A, et al. Interferon alfa treatment for pregnant women affected by essential thrombocythemia: case reports and a review. Am J Obstet Gynecol 2004;191:2016-2020.   DOI
95 van Genderen PJ, Mulder PG, Waleboer M, van de Moesdijk D, Michiels JJ. Prevention and treatment of thrombotic complications in essential thrombocythaemia: efficacy and safety of aspirin. Br J Haematol 1997;97:179-184.   DOI
96 van Genderen PJ, Prins FJ, Michiels JJ, Schror K. Thromboxane- dependent platelet activation in vivo precedes arterial thrombosis in thrombocythaemia: a rationale for the use of low-dose aspirin as an antithrombotic agent. Br J Haematol 1999;104:438-441.   DOI
97 Griesshammer M, Heimpel H, Pearson TC. Essential thrombocythemia and pregnancy. Leuk Lymphoma 1996;22 Suppl 1:57-63.   DOI
98 Delage R, Demers C, Cantin G, Roy J. Treatment of essential thrombocythemia during pregnancy with interferon- alpha. Obstet Gynecol 1996;87(5 Pt 2):814-817.   DOI
99 Milano V, Gabrielli S, Rizzo N, et al. Successful treatment of essential thrombocythemia in a pregnancy with recombinant interferon-alpha 2a. J Matern Fetal Med 1996;5:74-78.