Therapeutic approaches in myelofibrosis

Expert Opinion on Pharmacotherapy

Volumn 12, Issue 10, 2011, Pages 1597-1611

  Barosi, Giovanni ^a   Rosti, Vittorio ^a   Vannucchi, Alessandro M ^b  

^a FONDAZIONE IRCCS POLICLINICO SAN MATTEO   (Italy)

^b UNIVERSITY OF FLORENCE   (Italy)

Author keywords

demethylating agents; histone deacetylase inhibitors; JAK2 inhibitors; JAK2 V617F mutation; mTOR inhibitors; myelofibrosis; myeloproliferative neoplasm; response criteria

Indexed keywords

ALPHA INTERFERON; AZACITIDINE; BORTEZOMIB; BUSULFAN; CHLORAMBUCIL; CYCLOPHOSPHAMIDE; DANAZOL; DEPSIPEPTIDE; ETANERCEPT; GIVINOSTAT; HEMOGLOBIN; HYDROXYUREA; JANUS KINASE 2 INHIBITOR; LENALIDOMIDE; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; MELPHALAN; NOVEL ERYTHROPOIESIS STIMULATING PROTEIN; OBATOCLAX; PEGINTERFERON; PHOSPHORUS; POMALIDOMIDE; PREDNISONE; RECOMBINANT ALPHA2B INTERFERON; RECOMBINANT ERYTHROPOIETIN; SUNITINIB; THALIDOMIDE; TIOGUANINE; TIPIFARNIB; UNINDEXED DRUG; VORINOSTAT;

ACETYLATION; ANDROGEN THERAPY; ANEMIA; ANGIOGENESIS; ATAXIA; AUTOIMMUNE DISEASE; BLAST TRANSFORMATION; BLOOD TRANSFUSION; BONE MARROW SUPPRESSION; CARCINOGENESIS; CELL DEATH; CLINICAL ASSESSMENT; CONSTIPATION; CYSTITIS; CYTOGENETICS; CYTOPENIA; DISEASE ASSOCIATION; DNA METHYLATION; DOUBLE BLIND PROCEDURE; DRUG ACTIVITY; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG HALF LIFE; DRUG SAFETY; DRUG SOLUBILITY; DRUG STABILITY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DRY SKIN; EPIGENETICS; ERYTHROCYTE TRANSFUSION; FATIGUE; FEVER; FLU LIKE SYNDROME; FOLLOW UP; GASTROINTESTINAL SYMPTOM; GENE CONTROL; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HEMOGLOBIN BLOOD LEVEL; HIGH RISK PATIENT; HUMAN; IN VIVO STUDY; INFORMATION RETRIEVAL; LEG ULCER; LEUKEMIC TRANSFORMATION; LEUKOPENIA; LONG TERM CARE; LOW DRUG DOSE; MEDLINE; MEGAKARYOPOIESIS; MENTAL DISEASE; MOUTH ULCER; MULTIPLE CYCLE TREATMENT; MYALGIA; MYELOFIBROSIS; MYELOPROLIFERATIVE DISORDER; NAIL PIGMENTATION; NEUTROPENIA; OSTEOSCLEROSIS; PANCYTOPENIA; PERIPHERAL NEUROPATHY; PHASE 2 CLINICAL TRIAL (TOPIC); PNEUMONIA; RANDOMIZED CONTROLLED TRIAL (TOPIC); RASH; REVIEW; RISK ASSESSMENT; SKIN CANCER; SOMNOLENCE; SPLENOMEGALY; THROMBOCYTOPENIA; THROMBOEMBOLISM; THROMBOGENESIS; THROMBOSIS; THROMBOSIS PREVENTION; TREATMENT DURATION; TREATMENT INDICATION; TREATMENT RESPONSE; TUMOR CELL;

ANEMIA; ANIMALS; DRUG DELIVERY SYSTEMS; DRUG DESIGN; HUMANS; JANUS KINASE 2; MYELOPROLIFERATIVE DISORDERS; PRIMARY MYELOFIBROSIS; SPLENOMEGALY;

EID: 79958697713     PISSN: 14656566     EISSN: 17447666     Source Type: Journal    
DOI: 10.1517/14656566.2011.568939     Document Type: Review

References (96)

1. Mesa RA, Green A, Barosi G, et al. MPN-associated myelofibrosis (MPN-MF). Leuk Res 2010. [Epub ahead of print]
2. Vannucchi AM, Guglielmelli P, Tefferi A. Advances in understanding and management of myeloproliferative neoplasms. CA Cancer J Clin 2009;12:171-91
3. Lacout C, Pisani DF, Tulliez M, et al. JAK2V617F expression in murine hematopoietic cells leads to MPD mimicking human PV with secondary myelofibrosis. Blood 2006;108:1652-60 (Pubitemid 44316134)
4. Wernig G, Mercher T, Okabe R, et al. Expression of Jak2V617F causes a polycythemia vera-like disease with associated myelofibrosis in a murine bone marrow transplant model. Blood 2006;107:4274-81 (Pubitemid 43801351)
5. Marty C, Lacout C, Martin A, et al. Myeloproliferative neoplasm induced by constitutive expression of JAK2V617F in knock-in mice. Blood 2010;116:783-7
6. Mullally A, Lane SW, Ball B, et al. Physiological Jak2V617F expression causes a lethal myeloproliferative neoplasm with differential effects on hematopoietic stem and progenitor cells. Cancer Cell 2010;17:584-96
7. Barosi G, Bergamaschi G, Marchetti M, et al. JAK2 V617F mutational status predicts progression to large splenomegaly and leukemic transformation in primary myelofibrosis. Blood 2007;110:4030-6 (Pubitemid 350248459)
8. Guglielmelli P, Barosi G, Pieri L, et al. 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;94:144-6
9. Delhommeau F, Dupont S, Della Valle V, et al. Mutation in TET2 in myeloid cancers. N Engl J Med 2009;360:2289-301
10. Grand FH, Hidalgo-Curtis CE, Ernst T, et al. Frequent CBL mutations associated with 11q acquired uniparental disomy in myeloproliferative neoplasms. Blood 2009;113:6182-92
11. Carbuccia N, Murati A, Trouplin V, et al. Mutations of ASXL1 gene in myeloproliferative neoplasms. Leukemia 2009;23(11):2183-6
12. Green A, Beer P. Somatic mutations of IDH1 and IDH2 in the leukemic transformation of myeloproliferative neoplasms. N Engl J Med 2010;362:369-70
13. Tefferi A, Lasho TL, Abdel-Wahab O, et al. IDH1 and IDH2 mutation studies in 1473 patients with chronic-, fibroticor blast-phase essential thrombocythemia, polycythemia vera or myelofibrosis. Leukemia 2010;24:1302-9
14. Oh ST, Simonds EF, Jones C, et al. Novel mutations in the inhibitory adaptor protein LNK drive JAK-STAT signaling in patients with myeloproliferative neoplasms. Blood 2010;116:988-92
15. Ernst T, Chase AJ, Score J, et al. Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders. Nat Genet 2010;42:722-6
16. McNally RJ, Rowland D, Roman E, et al. Age and sex distributions of hematological malignancies in the U.K. Hematol Oncol 1997;15:173-89 (Pubitemid 28374886)
17. Cervantes F, Barosi G, Demory JL, et al. Myelofibrosis with myeloid metaplasia in young individuals: disease characteristics, prognostic factors and identification of risk groups. Br J Haematol 1998;102:684-90 (Pubitemid 28387050)
18. Gangat N, Caramazza D, Vaidya R, et al. DIPSS-Plus: a refined Dynamic International Prognostic Scoring System (DIPSS) for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count and transfusion status. J Clin Oncol [Epub ahead of print]
19. 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;113:2895-901
20. Barbui T, Carobbio A, Cervantes F, et al. Thrombosis in primary myelofibrosis: incidence and risk factors. Blood 2010;115:778-82
21. Barosi G, Bordessoule D, Briere J, et al. European Myelofibrosis Network. Response criteria for myelofibrosis with myeloid metaplasia: results of an initiative of the European Myelofibrosis Network (EUMNET). Blood 2005;106:2849-53 (Pubitemid 41510763)
22. Tefferi A, Barosi G, Mesa RA, et al. International Working Group (IWG) consensus criteria for treatment response in myelofibrosis with myeloid metaplasia, for the IWG for Myelofibrosis Research and Treatment (IWG-MRT). Blood 2006;108:1497-503 (Pubitemid 44316114)
23. Shimoda K, Shide K, Kamezaki K, et al. The effect of anabolic steroids on anemia in myelofibrosis with myeloid metaplasia: retrospective analysis of 39 patients in Japan. Int J Hematol 2007;85:338-43 (Pubitemid 47182062)
24. Cervantes F, Alvarez-Larran A, Domingo A, et al. 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;129:771-5 (Pubitemid 40904527)
25. Cervantes F, Alvarez-Larran A, Hernandez-Boluda JC, et al. Erythropoietin treatment of the anaemia of myelofibrosis with myeloid metaplasia: results in 20 patients and review of the literature. Br J Haematol 2004;127:399-403 (Pubitemid 39536591)
26. Tefferi A, Strand JJ, Lasho TL, et al. Respective clustering of unfavorable and favorable cytogenetic clones in myelofibrosis with myeloid metaplasia with homozygosity for JAK2(V617F) and response to erythropoietin therapy. Cancer 2006;106:1739-43
27. Tsiara SN, Chaidos A, Bourantas LK, et al. Recombinant human erythropoietin for the treatment of anaemia in patients with chronic idiopathic myelofibrosis. Acta Haematol 2006;117:156-61
28. 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;83:154-5
29. Huang J, Li CY, Mesa RA, et al. Risk factors for leukemic transformation in patients with primary myelofibrosis. Cancer 2008;112:2726-32 (Pubitemid 351969217)
30. Cervantes F, Alvarez-Larran A, Hernandez-Boluda JC, et al. Darbepoetin-alpha for the anaemia of myelofibrosis with myeloid metaplasia. Br J Haematol 2006;134:184-6 (Pubitemid 43893910)
31. Merup M, Kutti J, Birgerard G, et al. Negligible clinical effects of thalidomide in patients with myelofibrosis with myeloid metaplasia. Med Oncol 2002;19:79-86 (Pubitemid 34625929)
32. Barosi G, Elliott M, Canepa L, et al. Thalidomide in myelofibrosis with myeloid metaplasia: a pooled-analysis of individual patient data from 5 studies. Leuk Lymphoma 2002;43:2301-7
33. Mesa RA, Steensma DP, Pardanani A, et al. A phase II trial of combination low-dose thalidomide and prednisone for the treatment of myelofibrosis with myeloid metaplasia. Blood 2003;101:2534-41 (Pubitemid 36857609)
34. Marchetti M, Barosi G, Balestri F, et al. Low-dose thalidomide ameliorates cytopenias and splenomegaly in myelofibrosis with myeloid metaplasia: a phase II trial. J Clin Oncol 2004;22:424-31 (Pubitemid 41079770)
35. Abgrall JF, Guibaud I, Bastie JN, et al. Thalidomide versus placebo in myeloid metaplasia with myelofibrosis: a prospective, randomized, double-blind, multicenter study. Haematologica 2006;91:1027-32 (Pubitemid 44204767)
36. Thomas DA, Giles FJ, Albitar M, et al. Thalidomide therapy for myelofibrosis with myeloid metaplasia. Cancer 2006;106:1974-84 (Pubitemid 43673213)
37. Weinkove R, Reilly JT, McMullin MF, et al. Low-dose thalidomide in myelofibrosis. Haematologica 2008;93:1100-1 (Pubitemid 351957033)
38. Thapaliya P, Tefferi A, Pardanani A, et al. International working group for myelofibrosis research and treatment response assessment and long-term follow-up of 50 myelofibrosis patients treated with thalidomide-prednisone based regimens. Am J Hematol 2011;86:96-8
39. Mesa RA. How I treat symptomatic splenomegaly in patients with myelofibrosis. Blood 2009;113:5394-400
40. Sirhan S, Lasho TL, Hanson CA, et al. The presence of JAK2V617F in primary myelofibrosis or its allele burden in polycythemia vera predicts chemosensitivity to hydroxyurea. Am J Hematol 2008;83:363-5 (Pubitemid 351614747)
41. Martnez-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;89:1233-7
42. Saraceno R, Teoli M, Chimenti S. Hydroxyurea associated with concomitant occurrence of diffuse longitudinal melanonychia and multiple squamous cell carcinomas in an elderly subject. Clin Ther 2008;30:1324-9
43. Burkitt MJ, Raafat A. Nitric oxide generation from hydroxyurea: significance and implications for leukemogenesis in the management of myeloproliferative disorders. Blood 2006;107:2219-22 (Pubitemid 43345538)
44. Petti MC, Latagliata R, Spadea T, et al. Melphalan treatment in patients with myelofibrosis with myeloid metaplasia. Br J Haematol 2002;116:576-81 (Pubitemid 34178656)
45. Chee L, Kalnins R, Turner P. Low dose melphalan in the treatment of myelofibrosis: a single centre experience. Leuk Lymphoma 2006;47:1409-12 (Pubitemid 44269657)
46. Kiladjian JJ, Chomienne C, Fenaux P. Interferon-alpha therapy in bcr-abl-negative myeloproliferative neoplasms. Leukemia 2008;22:1990-8
47. Jabbour E, Kantarjian H, Cortes J, et al. PEG-IFN-alpha-2b therapy in BCR-ABL-negative myeloproliferative disorders: final result of a phase 2 study. Cancer 2007;110:2012-18 (Pubitemid 350036861)
48. Ianotto JC, Kiladjian JJ, Demory JL, et al. PEG-IFN-alpha-2a therapy in patients with myelofibrosis: a study of the French Groupe dEtudes des Myelofibroses (GEM) and France intergroupe des syndromes Myeloproliferatifs (FIM). Br J Haematol 2009;146:223-5
49. Silver RT, Vandris K. Recombinant interferon alpha (rIFN alpha-2b) may retard progression of early primary myelofibrosis. Leukemia 2009;23:1366-9
50. Xiong Z, Yan Y, Liu E, et al. Novel tumor antigens elicit anti-tumor humoral immune reactions in a subset of patients with polycythemia vera. Clin Immunol 2007;122:279-87 (Pubitemid 46216913)
51. Tefferi A, Cortes J, Verstovsek S, et al. Lenalidomide therapy in myelofibrosis with myeloid metaplasia. Blood 2006;108:1158-64 (Pubitemid 44232010)
52. Quintas-Cardama A, Kantarjian H, Manshouri T, et al. Lenalidomide plus prednisone results in durable clinical, histopathologic, and molecular responses in patients with myelofibrosis. J Clin Oncol 2009;27:4760-6
53. Mesa RA, Yao X, Cripe LD, et al. Lenalidomide and prednisone for myelofibrosis: Eastern Cooperative Oncology Group (ECOG) phase-2 trial E4903. Blood 2010;116:4436-8
54. Tefferi A, Verstovsek S, Barosi G, et al. Pomalidomide is active in the treatment of anemia associated with myelofibrosis. J Clin Oncol 2009;27:4563-69
55. Begna KH, Mesa RA, Pardanani A, et al. A phase-2 trial of low-dose pomalidomide in myelofibrosis. Leukemia 2011;25:301-4
56. Mesa RA, Pardanani AD, Hussein K, et al. Phase1/-2 study of Pomalidomide in myelofibrosis. Am J Hematol 2010;85:129-30
57. Mesa RA, Camoriano JK, Geyer SM, et al. A phase II trial of tipifarnib in myelofibrosis: primary, post-polycythemia vera and post-essential thrombocythemia. Leukemia 2007;21:1964-70 (Pubitemid 47299971)
58. Mesa RA, Verstovsek S, Rivera C, et al. Bortezomib therapy in myelofibrosis: a phase II clinical trial. Leukemia 2008;22:1636-38
59. Barosi G, Gattoni E, Guglielmelli P, et al. Myeloproliferative research consortium. Phase I/II study of single-agent bortezomib for the treatment of patients with myelofibrosis. Clinical and biological effects of proteasome inhibition. Am J Hematol 2010;85:616-19
60. Parikh SA, Kantarjian H, Schimmer A, et al. Phase II study of obatoclax mesylate (GX15-070), a small-molecule BCL-2 family antagonist, for patients with myelofibrosis. Clin Lymphoma Myeloma Leuk 2010;10:285-9
61. Apostolidou E, Kantarjian H, Thomas D, et al. Phase II study of sunitinib in patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis. Clin Lymphoma Myeloma Leuk 2010;10:281-4
62. Vannucchi AM, Guglielmelli P, Rambaldi A, et al. Epigenetic therapy in myeloproliferative neoplasms: evidence and perspectives. J Cell Mol Med 2009;13:1437-50
63. Bogani C, Ponziani V, Guglielmelli P, et al. Myeloproliferative disorders research consortium. Hypermethylation of CXCR4 promoter in CD34+ cells from patients with primary myelofibrosis. Stem Cells 2008;26:1920-30
64. Ihalainen J, Juvonen E, Savolainen ER, et al. Calcitonin gene methylation in chronic myeloproliferative disorders. Leukemia 1994;8:230-5 (Pubitemid 24057535)
65. Wang JC, Chen W, Nallusamy S, et al. Hypermethylation of the P15INK4b and P16INK4a in agnogenic myeloid metaplasia (AMM) and AMM in leukaemic transformation. Br J Haematol 2002;116:582-6 (Pubitemid 34178657)
66. Kumagai T, Tefferi A, Jones L, et al. Methylation analysis of the cell cycle control genes in myelofibrosis with myeloid metaplasia. Leuk Res 2005;29:511-15 (Pubitemid 40327239)
67. Jones LC, Tefferi A, Idos GE, et al. RARbeta2 is a candidate tumor suppressor gene in myelofibrosis with myeloid metaplasia. Oncogene 2004;23:7846-53 (Pubitemid 39457034)
68. Fourouclas N, Li J, Gilby DC, et al. Methylation of the suppressor of cytokine signaling 3 gene (SOCS3) in myeloproliferative disorders. Haematologica 2008;93:1635-44
69. Shi J, Zhao Y, Ishii T, et al. Effects of chromatin-modifying agents on CD34+ cells from patients with idiopathic myelofibrosis. Cancer Res 2007;67:6417-24 (Pubitemid 47037526)
70. Wang X, Zhang W, Ishii T, et al. Correction of the abnormal trafficking of primary myelofibrosis CD34+ cells by treatment with chromatin-modifying agents. Cancer Res 2009;69:7612-18
71. Mesa RA, Verstovsek S, Rivera C, et al. 5-Azacitidine has limited therapeutic activity in myelofibrosis. Leukemia 2009;23:180-2
72. Danilov AV, Relias V, Feeney DM, et al. Decitabine is an effective treatment of idiopathic myelofibrosis. Br J Haematol 2009;145:131-2
73. Guerini V, Barbui V, Spinelli O, et al. The histone deacetylase inhibitor ITF2357 selectively targets cells bearing mutated JAK2(V617F). Leukemia 2008;22:740-7 (Pubitemid 351552623)
74. Amaru A, Todoerti K, Pellicioli A, et al. The HDAC inhibitor ITF2357 modulates key hematopoetic genes in JAK2V617F cells from myeloproliferative neoplasm patients. ASH Annual Meeting Abstracts. Blood 2010;116:348
75. Rambaldi A, Dellacasa CM, Finazzi G, et al. A pilot study of the Histone-Deacetylase inhibitor Givinostat in patients with JAK2V617F positive chronic myeloproliferative neoplasms. Br J Haematol 2010;150:446-55
76. Wang Y, Fiskus W, Chong DG, et al. Cotreatment with panobinostat and JAK2 inhibitor TG101209 attenuates JAK2V617F levels and signaling and exerts synergistic cytotoxic effects against human myeloproliferative neoplastic cells. Blood 2009;114:5024-33
77. Mascarenhas J, Wang X, Rodriguez A, et al. A phase I study of LBH589, a novel histone deacetylase inhibitor in patients with primary myelofibrosis (PMF) and post-polycythemia/essential thrombocythemia myelofibrosis (Post- PV/ET MF). ASH Annual Meeting Abstracts. Blood 2009;114:130
78. DeAngelo DJ, Tefferi A, Fiskus W, et al. A phase II trial of panobinostat, an orally available deacetylase inhibitor (DACi), in patients with primary myelofibrosis (PMF), post essential thrombocythemia (ET), and post polycythemia vera (PV) myelofibrosis. ASH Annual Meeting Abstracts. Blood 2010;116:276
79. Vannucchi AM, Bogani C, Bartalucci N, et al. The mTOR inhibitor, RAD001, inhibits the growth of cells from patients with myeloproliferative neoplasms. ASH Annual Meeting Abstracts. Blood 2009;114:2914
80. Vannucchi AM, Guglielmelli P, Lupo L, et al. A phase 1/2 study of RAD001, a mTOR inhibitor, in patients with myelofibrosis: final results. ASH Annual Meeting Abstracts. Blood 2010;116:314
81. Quintas-Cardama A, Vaddi K, Liu P, et al. Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood 2010;115:3109-17
82. Verstovsek S, Kantarjian H, Mesa RA, et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med 2010;363:1117-27
83. Hexner EO, Serdikoff C, Jan M, et al. Lestaurtinib (CEP701) is a JAK2 inhibitor that suppresses JAK2/STAT5 signaling and the proliferation of primary erythroid cells from patients with myeloproliferative disorders. Blood 2008;111:5663-71
84. Santos FP, Kantarjian HM, Jain N, et al. Phase 2 study of CEP-701, an orally available JAK2 inhibitor, in patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis. Blood 2010;115:1131-6
85. Lasho TL, Tefferi A, Hood JD, et al. TG101348, a JAK2-selective antagonist, inhibits primary hematopoietic cells derived from myeloproliferative disorder patients with JAK2V617F, MPLW515K or JAK2 exon 12 mutations as well as mutation negative patients. Leukemia 2008;22:1790-2
86. Wernig G, Kharas MG, Okabe R, et al. Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera. Cancer Cell 2008;13:311-20 (Pubitemid 351446195)
87. Pardanani A, Gotlib JR, Jamieson C, et al. Safety and efficacy of TG101348, a selective JAK2 inhibitor, in myelofibrosis. J Clin Oncol 2011. [Epub ahead of print]
88. Pardanani A, Gotlib JR, Jamieson C, et al. Longer-term follow-up with TG101348 therapy in myelofibrosuis confiorms sustained improvement in splenomegaly, disease-related symptoms, and JAK2V617F allele burden. ASH Annual Meeting Abstracts. Blood 2010;116:1271
89. Verstovsek S, Deeg J, Odenike O, et al. Phase 1-2 study of SB1518, a novel JAK2/FLT3 inhibitor, in the treatment of primary myelofibrosis. ASH Annual Meeting Abstracts. Blood 2010;116:205
90. Pardanani A, Lasho T, Smith G, et al. CYT387, a selective JAK1/JAK2 inhibitor: in vitro assessment of kinaseselectivity and preclinical studies using cell lines and primary cells from polycythemia vera patients. Leukemia 2009;23:1441-5
91. Tyner JW, Bumm TG, Deininger J, et al. CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms. Blood 2010;115:5232-40
92. Pardanani A, George G, Lasho T, et al. A Phase I/II study of CYT387, an oral JAK-1/2 inhibitor, in myelofibrosis: significant response rates in anemia, splenomegaly, and constitutional symptoms. ASH Annual Meeting Abstracts. Blood 2010;116:206
93. Shah NP, Olszynski P, Sokol L, et al. A phase I study of XL019, a selective JAK2 inhibitor, in patients with primary myelofibrosis, post-polycythemia vera, or post-essential thrombocythemia myelofibrosis. ASH Annual Meeting Abstracts. Blood 2008;112:98a
94. Giles FJ, List AF, Carroll M, et al. PTK787/ZK 222584, a small molecule tyrosine kinase receptor inhibitor of vascular endothelial growth factor (VEGF), has modest activity in myelofibrosis with myeloid metaplasia. Leuk Res 2007;7:891-7 (Pubitemid 46856729)
95. Gale RP, Barosi G, Barbui T, et al. What are RBC-transfusion-dependence and -independence? Leuk Res 2011;35:8-11
96. 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;33:1199-203