Primary myelofibrosis: 2021 update on diagnosis, risk‐stratification and management

American Journal of Hematology - Tập 96 Số 1 - Trang 145-162 - 2021
Ayalew Tefferi1
1Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA

Tóm tắt

AbstractDisease OverviewPrimary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by stem cell‐derived clonal myeloproliferation that is often but not always accompanied by JAK2, CALR, or MPL mutations. Additional disease features include bone marrow reticulin/collagen fibrosis, aberrant inflammatory cytokine expression, anemia, hepatosplenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, leukemic progression, and shortened survival.DiagnosisBone marrow morphology is the primary basis for diagnosis. Presence of JAK2, CALR, or MPL mutation, expected in around 90% of the patients, is supportive but not essential for diagnosis; these mutations are also prevalent in the closely related MPNs, namely polycythemia vera (PV) and essential thrombocythemia (ET). The 2016 World Health Organization classification system distinguishes “prefibrotic” from “overtly fibrotic” PMF; the former might mimic ET in its presentation. Furthermore, approximately 15% of patients with ET or PV might progress into a PMF‐like phenotype (post‐ET/PV MF) during their clinical course.Adverse MutationsSRSF2, ASXL1, and U2AF1‐Q157 mutations predict inferior survival in PMF, independent of each other and other risk factors. RAS/CBL mutations predicted resistance to ruxolitinib therapy.Adverse KaryotypeVery high risk abnormalities include −7, inv (3), i(17q), +21, +19, 12p‐, and 11q‐.Risk StratificationTwo new prognostic systems for PMF have recently been introduced: GIPSS (genetically‐inspired prognostic scoring system) and MIPSS70+ version 2.0 (MIPSSv2; mutation‐ and karyotype‐enhanced international prognostic scoring system). GIPSS is based exclusively on mutations and karyotype. MIPSSv2 includes, in addition, clinical risk factors. GIPSS features four and MIPSSv2 five risk categories.Risk‐adapted TherapyObservation alone is advised for MIPSSv2 “low” and “very low” risk disease (estimated 10‐year survival 56%‐92%); allogeneic hematopoietic stem cell transplant (AHSCT) is the preferred treatment for “very high” and “high” risk disease (estimated 10‐year survival 0%‐13%); treatment‐requiring patients with intermediate‐risk disease (estimated 10‐year survival 30%) are best served by participating in clinical trials. In non‐transplant candidates, conventional treatment for anemia includes androgens, prednisone, thalidomide, and danazol; for symptomatic splenomegaly, hydroxyurea and ruxolitinib; and for constitutional symptoms, ruxolitinib. Fedratinib, another JAK2 inhibitor, has now been FDA‐approved for use in ruxolitinib failures. Splenectomy is considered for drug‐refractory splenomegaly and involved field radiotherapy for non‐hepatosplenic EMH and extremity bone pain.New DirectionsA number of new agents, alone or in combination with ruxolitinib, are currently under investigation for MF treatment (ClinicalTrials.gov); preliminary results from some of these clinical trials were presented at the 2020 ASH annual meeting and highlighted in the current document.

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Tài liệu tham khảo

10.1182/blood-2016-03-643544

10.1038/s41408-018-0054-y

10.1002/ajh.24684

10.1111/bjh.14838

10.1182/blood-2017-01-761999

10.1002/ajh.24482

10.1038/sj.leu.2404914

10.1038/leu.2017.268

10.1038/leu.2013.119

10.1182/bloodadvances.2016000208

10.1182/bloodadvances.2016000216

10.1182/bloodadvances.2018015875

10.1038/s41375-018-0019-y

10.1056/NEJM200004273421706

10.1200/JCO.2004.00.9316

10.1002/ajh.21543

10.1038/s41375-018-0018-z

10.1001/jamaoncol.2015.89

10.1200/JCO.2010.34.5298

10.1002/ajh.24253

10.1002/ajh.24396

10.1038/modpathol.3800348

10.1002/ajh.10258

10.1182/blood-2008-07-170449

10.1182/blood-2009-09-245837

10.1200/JCO.2010.32.2446

10.1200/JCO.2018.78.9867

10.1038/s41375-018-0107-z

10.1200/JCO.2017.76.4886

10.1002/ajh.24978

10.1038/leu.2014.57

10.1038/leu.2014.76

10.1038/leu.2017.318

10.1038/s41375-018-0078-0

10.1038/s41375-018-0028-x

10.1182/bloodadvances.2020002175

10.1038/s41375-019-0603-9

10.1002/ajh.25053

10.1016/j.bbmt.2009.10.025

10.1182/blood-2013-02-485888

10.1056/NEJMe1115119

10.1182/blood-2011-11-395228

10.1056/NEJMc1109555

10.1038/s41408-018-0067-6

10.1038/leu.2017.330

10.1182/blood-2014-10-608315

10.1182/bloodadvances.2018026658

Silverstein MN, 1975, Agnogenic Myeloid Metaplasia, 126

10.1097/PPO.0b013e31815a7c0a

10.1046/j.1365-2141.2002.03443.x

10.1002/cncr.21827

10.1182/blood-2002-09-2928

10.1182/blood-2006-02-004572

10.1200/JCO.2009.22.6548

10.1111/j.1600-0609.2009.01266.x

10.1038/sj.leu.2404711

10.1002/ajh.22233

10.1007/s00277-010-1019-9

10.1182/blood.V97.6.1896

10.1056/NEJMoa1002028

10.1002/ajh.24614

10.1056/NEJMoa1110557

10.1056/NEJMoa1110556

10.1002/ajh.24775

10.1038/leu.2016.148

10.1182/blood-2013-10-531103

10.2169/internalmedicine.9165-17

10.1002/ajh.24688

10.1038/s41409-017-0081-5

10.1002/ajh.25063

10.1002/ajh.24971

10.1111/bjh.16576

10.1002/ajh.25777

10.1001/jamaoncol.2015.1590

10.1016/S2352-3026(17)30027-3

10.1001/jamaoncol.2017.5818

10.1200/JCO.2017.73.4418

10.1016/S2352-3026(17)30237-5

10.1182/bloodadvances.2020002662

10.3324/haematol.2018.209965

10.1182/blood-2019-123244

10.1200/JCO.2019.37.15_suppl.7056

10.1056/NEJMoa1310523

10.1158/1078-0432.CCR-19-1005

10.1038/nm.3995

10.1111/bjh.17084

10.1016/S2152-2650(20)30493-6

10.1016/S2152-2650(20)31008-9

10.1182/blood-2009-07-234880

10.1016/j.bbmt.2017.09.016

10.1016/j.bbmt.2019.06.034

10.1016/j.bbmt.2017.03.002

10.1002/ajh.26034

Polverelli N, 2020, Impact of spleen size and splenectomy on outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis: a retrospective analysis by the chronic malignancies working party on behalf of European society for blood and marrow transplantation (EBMT), Am J Hematol, 96, 69, 10.1002/ajh.26020

10.1007/s12032-019-1245-5

10.1080/10428194.2017.1321747

10.1111/ejh.13099

10.1038/leu.2014.86

10.1038/bmt.2015.295

10.1016/j.bbmt.2015.10.005

10.1182/blood.V95.7.2226

10.1002/cncr.22021

10.1002/ajh.25203

Barosi G, 1998, Splenectomy and risk of blast transformation in myelofibrosis with myeloid metaplasia. Italian Cooperative Study Group on Myeloid with Myeloid Metaplasia, Blood, 91, 3630

10.1002/ajh.24881

10.1046/j.1365-2141.1998.00998.x

10.4065/78.10.1223

10.1046/j.1365-2141.2002.03695.x

10.1002/ajh.21819

10.1159/000338949

10.1111/j.1600-0609.2010.01480.x

10.1038/s41408-019-0175-y

10.1016/j.leukres.2020.106456

10.1002/ajh.24221

10.1182/blood-2011-04-349142

10.1002/ajh.25000

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American Journal of Hematology

Tập 96 Số 1

145-162

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