Treatment options for hydroxyurea-refractory disease complications in myeloproliferative neoplasms: JAK2 inhibitors, radiotherapy, splenectomy and transjugular intrahepatic portosystemic shunt

European Journal of Haematology

Volumn 85, Issue 3, 2010, Pages 192-199

  Mishchenko, Elena ^a   Tefferi, Ayalew ^b  

^a BNAI ZION MEDICAL CENTER   (Israel)

^b MAYO CLINIC   (United States)

Author keywords

extramedullary hematopoiesis; JAK2; radiation; splenectomy; transjugular intrahepatic portosystemic shunt; treatment

Indexed keywords

ALPHA INTERFERON; ANTIHISTAMINIC AGENT; AZD1480; CYT387; FLT3 LIGAND; INCB018424; INTERLEUKIN 1BETA; INTERLEUKIN 6; JANUS KINASE 1; JANUS KINASE 2; JANUS KINASE 3; JANUS KINASE INHIBITOR; LESTAURTINIB; NARCOTIC AGENT; NONSTEROID ANTIINFLAMMATORY AGENT; SB1518; SEROTONIN UPTAKE INHIBITOR; TG101348; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; XL019; HYDROXYUREA; JAK2 PROTEIN, HUMAN; PROTEIN KINASE INHIBITOR;

ABDOMINAL DISEASE; ANEMIA; APPETITE DISORDER; ASCITES; BLEEDING; BODY MASS; BONE PAIN; BUDD CHIARI SYNDROME; CACHEXIA; DIARRHEA; ERYTHROCYTE TRANSFUSION; EXTRAMEDULLARY HEMATOPOIESIS; FATIGUE; FOLLOW UP; GASTROINTESTINAL SYMPTOM; HEPATOMEGALY; HEPATOSPLENOMEGALY; HUMAN; INFECTION; LEUKOCYTOSIS; LIVER CIRRHOSIS; LIVER VENOOCCLUSIVE DISEASE; LUNG DISEASE; MYELOFIBROSIS; MYELOPROLIFERATIVE DISORDER; NAUSEA AND VOMITING; NIGHT SWEAT; OPTIMAL DRUG DOSE; PELVIC DISEASE; PHOTOTHERAPY; PLEURA DISEASE; POLYCYTHEMIA VERA; PORTAL HYPERTENSION; PRIORITY JOURNAL; PRURITUS; PULMONARY HYPERTENSION; RADIATION DOSE; REVIEW; SIDE EFFECT; SPLENECTOMY; SPLENOMEGALY; THROMBOCYTHEMIA; THROMBOCYTOPENIA; THROMBOCYTOSIS; THROMBOSIS; TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT; WEIGHT REDUCTION; ANTAGONISTS AND INHIBITORS; COMPLICATION; MYELOPROLIFERATIVE DISORDERS;

HUMANS; HYDROXYUREA; JANUS KINASE 2; MYELOPROLIFERATIVE DISORDERS; PORTASYSTEMIC SHUNT, TRANSJUGULAR INTRAHEPATIC; PROTEIN KINASE INHIBITORS; SPLENECTOMY;

EID: 77955828956     PISSN: 09024441     EISSN: 16000609     Source Type: Journal    
DOI: 10.1111/j.1600-0609.2010.01480.x     Document Type: Review

References (71)

1. James C, Ugo V, Le Couedic JP, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 2005 434 : 1144 8.
2. 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.
3. Tefferi A. Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1. Leukemia 2010 24 : 1128 38.
4. Pardanani A. JAK2 inhibitor therapy in myeloproliferative disorders: rationale, preclinical studies and ongoing clinical trials. Leukemia 2008 22 : 23 30.
5. Gangat N, Strand J, Li CY, Wu W, Pardanani A, Tefferi A. Leucocytosis in polycythaemia vera predicts both inferior survival and leukaemic transformation. Br J Haematol 2007 138 : 354 8.
6. Passamonti F, Rumi E, Pungolino E, Malabarba L, Bertazzoni P, Valentini M, et al. Life expectancy and prognostic factors for survival in patients with polycythemia vera and essential thrombocythemia. Am J Med 2004 117 : 755 61.
7. Gangat N, Wolanskyj AP, McClure RF, Li CY, Schwager S, Wu W, et al. Risk stratification for survival and leukemic transformation in essential thrombocythemia: a single institutional study of 605 patients. Leukemia 2007 21 : 270 6.
8. Passamonti F, Rumi E, Arcaini L, Boveri E, Elena C, Pietra D, et al. Prognostic factors for thrombosis, myelofibrosis, and leukemia in essential thrombocythemia: a study of 605 patients. Haematologica 2008 93 : 1645 51.
9. Finazzi G, Barbui T. Evidence and expertise in the management of polycythemia vera and essential thrombocythemia. Leukemia 2008 22 : 1494 502.
10. Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C, et al. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med 2004 350 : 114 24.
11. Cortelazzo S, Finazzi G, Ruggeri M, Vestri O, Galli M, Rodeghiero F, et al. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med 1995 332 : 1132 6.
12. Harrison CN, Campbell PJ, Buck G, Wheatley K, East CL, Bareford D, et al. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med 2005 353 : 33 45.
13. Berk PD, Wasserman LR, Fruchtman SM, Goldberg JD. Treatment of polycythemia vera: a summary of clinical trials conducted by the polycythemia vera study group. In : Wasserman LR, Berk PD, Berlin NI, eds. Polycythemia Vera and the Myeloproliferative Disorders.
14. Quintas-Cardama A, Kantarjian H, Manshouri T, Luthra R, Estrov Z, Pierce S, et al. Pegylated interferon alfa-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera. J Clin Oncol 2009 27 : 5418 24.
15. Kiladjian JJ, Cassinat B, Chevret S, Turlure P, Cambier N, Roussel M, et al. Pegylated interferon-alfa-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera. Blood 2008 112 : 3065 72.
16. Shvidel L, Sigler E, Haran M, Klepfish A, Duek A, Berrebi A, et al. Busulphan is safe and efficient treatment in elderly patients with essential thrombocythemia. Leukemia 2007 21 : 2071 2.
17. Treatment of polycythaemia vera by radiophosphorus or busulphan: a randomized trial. "Leukemia and Hematosarcoma" Cooperative Group, European Organization for Research on Treatment of Cancer (E.O.R.T.C.). Br J Cancer 1981 44 : 75 80.
18. Cervantes F, Dupriez B, Pereira A, Passamonti F, Reilly JT, Morra E, 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.
19. Vaidya R, Siragusa S, Huang J, Schwager SM, Hanson CA, Hussein K, et al. Mature survival data for 176 patients younger than 60 years with primary myelofibrosis diagnosed between 1976 and 2005: evidence for survival gains in recent years. Mayo Clin Proc 2009 84 : 1114 9.
20. Tefferi A, Verstovsek S, Barosi G, Passamonti F, Roboz GJ, Gisslinger H, et al. Pomalidomide is active in the treatment of anemia associated with myelofibrosis. J Clin Oncol 2009 27 : 4563 9.
21. Mesa RA, Pardanani AD, Hussein K, Wu W, Schwager S, Litzow MR, et al. Phase1-2 study of Pomalidomide in myelofibrosis. Am J Hematol 2010 85 : 129 30.
22. Tefferi A, Siragusa S, Hussein K, Schwager SM, Hanson CA, Pardanani A, et al. Transfusion-dependency at presentation and its acquisition in the first year of diagnosis are both equally detrimental for survival in primary myelofibrosis-prognostic relevance is independent of IPSS or karyotype. Am J Hematol 2009 85 : 14 7.
23. Hussein K, Pardanani AD, Van Dyke DL, Hanson CA, Tefferi A. International Prognostic Scoring System-independent cytogenetic risk categorization in primary myelofibrosis. Blood 2010 115 : 496 9.
24. Mesa RA, Niblack J, Wadleigh M, Verstovsek S, Camoriano J, Barnes S, 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.
25. Mesa RA, Schwager S, Radia D, Cheville A, Hussein K, Niblack J, 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.
26. Pardanani A, Lasho T, Smith G, Burns CJ, Fantino E, Tefferi A. CYT387, a selective JAK1JAK2 inhibitor: in vitro assessment of kinase selectivity and preclinical studies using cell lines and primary cells from polycythemia vera patients. Leukemia 2009 23 : 1441 5.
27. Hedvat M, Huszar D, Herrmann A, Gozgit JM, Schroeder A, Sheehy A, et al. The JAK2 inhibitor AZD1480 potently blocks Stat3 signaling and oncogenesis in solid tumors. Cancer Cell 2009 16 : 487 97.
28. Shah NP, Olszynski P, Sokol L, Verstovsek S, Hoffman R, List AF, 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 2008 112 : 98.
29. Verstovsek S, Odenike O, Scott B, Estrov Z, Cortes J, Thomas DA, et al. Phase I Dose-Escalation Trial of SB1518, a Novel JAK2FLT3 Inhibitor, in Acute and Chronic Myeloid Diseases, Including Primary or Post-Essential ThrombocythemiaPolycythemia Vera Myelofibrosis. ASH Annual Meeting Abstracts 2009 114 : 3905.
30. Santos FP, Kantarjian HM, Jain N, Manshouri T, Thomas DA, Garcia-Manero G, et al. Phase 2 study of CEP-701, an orally available JAK2 inhibitor, in patients with primary or post-polycythemia veraessential thrombocythemia myelofibrosis. Blood 2010 115 : 1131 6.
31. Moliterno AR, Hexner E, Roboz GJ, Carroll M, Luger S, Mascarenhas J, et al. An open-label study of CEP-701 in patients with JAK2 V617F-positive PV and ET: update of 39 enrolled patients. ASH Annual Meeting Abstracts 2009 114 : 753.
32. Pardanani AD, Gotlib JR, Jamieson C, Cortes J, Talpaz M, Stone R, et al. A phase I evaluation of TG101348, a selective JAK2 inhibitor, in myelofibrosis: clinical response is accompanied by significant reduction in JAK2V617F allele burden. ASH Annual Meeting Abstracts 2009 114 : 755.
33. Verstovsek S, Kantarjian H, Mesa RA, Cortes-Franco J, Pardanani AD, Thomas DA, et al. Long-term follow up and optimized dosing regimen of INCB018424 in patients with myelofibrosis: durable clinical, functional and symptomatic responses with improved hematological safety. ASH Annual Meeting Abstracts 2009 114 : 756.
34. Verstovsek S, Passamonti F, Rambaldi A, Barosi G, Rosen P, Levy R, et al. A Phase 2 Study of INCB018424, An Oral, Selective JAK1JAK2 Inhibitor, in Patients with Advanced Polycythemia Vera (PV) and Essential Thrombocythemia (ET) Refractory to Hydroxyurea. ASH Annual Meeting Abstracts 2009 114 : 311.
35. Tefferi A, Kantarjian HM, Pardanani AD, Mesa RA, Newton RC, Scherle PA, et al. The Clinical Phenotype of Myelofibrosis Encompasses a Chronic Inflammatory State That Is Favorably Altered by INCB018424, a Selective Inhibitor of JAK12. ASH Annual Meeting Abstracts 2008 112 : 2804.
36. Rambaldi A, Dellacasa CM, Salmoiraghi S, Spinelli O, Ferrari ML, Gattoni E, et al. A Phase 2A study of the Histone-Deacetylase Inhibitor ITF2357 in Patients with Jak2V617F Positive Chronic Myeloproliferative Neoplasms. ASH Annual Meeting Abstracts 2008 112 : 100.
37. Vannucchi AM, Guglielmelli P, Gattoni E, Antonioli E, Bogani C, Tozzi L, et al. RAD001, An Inhibitor of mTOR, Shows Clinical Activity in a Phase III Study in Patients with Primary Myelofibrosis (PMF) and Post Polycythemia VeraEssential Thrombocythemia Myelofibrosis (PPVPET MF). ASH Annual Meeting Abstracts 2009 114 : 307.
38. Diehn F, Tefferi A. Pruritus in polycythaemia vera: prevalence, laboratory correlates and management. Br J Haematol 2001 115 : 619 21.
39. Tefferi A, Fonseca R. Selective serotonin reuptake inhibitors are effective in the treatment of polycythemia vera-associated pruritus. Blood 2002 99 : 2627.
40. Muller EW, de Wolf JT, Egger R, Wijermans PW, Huijgens PC, Halie MR, et al. Long-term treatment with interferon-alpha 2b for severe pruritus in patients with polycythaemia vera. Br J Haematol 1995 89 : 313 8.
41. Jeanmougin M, Rain JD, Najean Y. Efficacy of photochemotherapy on severe pruritis in polycythemia vera. Ann Hematol 1996 73 : 91 3.
42. Koch CA, Li CY, Mesa RA, Tefferi A. Nonhepatosplenic extramedullary hematopoiesis: associated diseases, pathology, clinical course, and treatment. Mayo Clin Proc 2003 78 : 1223 33.
43. Steensma DP, Hook CC, Stafford SL, Tefferi A. Low-dose, single-fraction, whole-lung radiotherapy for pulmonary hypertension associated with myelofibrosis with myeloid metaplasia. Br J Haematol 2002 118 : 813 6.
44. Jyothirmayi R, Coltart S. An audit of the indications for and techniques of palliative splenic radiotherapy in the UK. Clin Oncol (R Coll Radiol) 2005 17 : 192 4.
45. Weinmann M, Becker G, Einsele H, Bamberg M. Clinical indications and biological mechanisms of splenic irradiation in chronic leukaemias and myeloproliferative disorders. Radiother Oncol 2001 58 : 235 46.
46. Elliott MA, Chen MG, Silverstein MN, Tefferi A. Splenic irradiation for symptomatic splenomegaly associated with myelofibrosis with myeloid metaplasia. Br J Haematol 1998 103 : 505 11.
47. Bouabdallah R, Coso D, Gonzague-Casabianca L, Alzieu C, Resbeut M, Gastaut JA. Safety and efficacy of splenic irradiation in the treatment of patients with idiopathic myelofibrosis: a report on 15 patients. Leuk Res 2000 24 : 491 5.
48. Tefferi A, Jimenez T, Gray LA, Mesa RA, Chen MG. Radiation therapy for symptomatic hepatomegaly in myelofibrosis with myeloid metaplasia. Eur J Haematol 2001 66 : 37 42. (Pubitemid 32099408)
49. Riesterer O, Gmur J, Lutolf U. Repeated and preemptive palliative radiotherapy of symptomatic hepatomegaly in a patient with advanced myelofibrosis. Onkologie 2008 31 : 325 7.
50. Dingli D, Utz JP, Krowka MJ, Oberg AL, Tefferi A. Unexplained Pulmonary Hypertension in Chronic Myeloproliferative Disorders. Chest 2001 120 : 801 8.
51. Neben-Wittich M, Brown P, Tefferi A. Successful Treatment of Severe Extremity Pain in Myelofibrosis With Low-Dose Single-Fraction Radiation Therapy. Am J Clin Oncol-Cancer Clin Trials 2010 33 : 203 4.
52. Mesa RA, Nagorney DS, Schwager S, Allred J, Tefferi A. Palliative goals, patient selection, and perioperative platelet management: outcomes and lessons from 3 decades of splenectomy for myelofibrosis with myeloid metaplasia at the Mayo Clinic. Cancer 2006 107 : 361 70.
53. Tefferi A, Mesa RA, Nagorney DM, Schroeder G, Silverstein MN. Splenectomy in myelofibrosis with myeloid metaplasia: a single-institution experience with 223 patients. Blood 2000 95 : 2226 33.
54. Feldman LS, Demyttenaere SV, Polyhronopoulos GN, Fried GM. Refining the selection criteria for laparoscopic versus open splenectomy for splenomegaly. J Laparoendosc Adv Surg Tech A 2008 18 : 13 9.
55. Iwase K, Higaki J, Mikata S, Tanaka Y, Yoshikawa M, Hori S, et al. Laparoscopically assisted splenectomy following preoperative splenic artery embolization using contour emboli for myelofibrosis with massive splenomegaly. Surg Laparosc Endosc Percutan Tech 1999 9 : 197 202.
56. Hiatt JR, Gomes AS, Machleder HI. Massive splenomegaly. Superior results with a combined endovascular and operative approach. Arch Surg 1990 125 : 1363 7.
57. Hocking WG, Machleder HI, Golde DW. Splenic artery embolization prior to splenectomy in end-stage polycythemia vera. Am J Hematol 1980 8 : 123 7.
58. Barosi G, Ambrosetti A, Centra A, Falcone A, Finelli C, Foa P, et al. Splenectomy and risk of blast transformation in myelofibrosis with myeloid metaplasia. Italian Cooperative Study Group on Myeloid with Myeloid Metaplasia. Blood 1998 91 : 3630 6.
59. Riggio O, Ridola L, Lucidi C, Angeloni S. Emerging issues in the use of transjugular intrahepatic portosystemic shunt (TIPS) for management of portal hypertension: time to update the guidelines? Dig Liver Dis 2009 [Epub ahead of print].
60. Doki N, Irisawa H, Takada S, Sakura T, Miyawaki S. Transjugular intrahepatic portosystemic shunt for the treatment of portal hypertension due to idiopathic myelofibrosis. Intern Med 2007 46 : 187 90.
61. Angermayr B, Cejna M, Schoder M, Wrba F, Valent P, Gangl A, et al. Transjugular intrahepatic portosystemic shunt for treatment of portal hypertension due to extramedullary hematopoiesis in idiopathic myelofibrosis. Blood 2002 99 : 4246 7.
62. Belohlavek J, Schwarz J, Jirasek A, Krajina A, Polak F, Hruby M. Idiopathic myelofibrosis complicated by portal hypertension treated with a transjugular intrahepatic portosystemic shunt (TIPS). Wien Klin Wochenschr 2001 113 : 208 11.
63. Tanaka N, Yamakado K, Kihira H, Hashimoto A, Murayama T, Takeda K. Re: transjugular intrahepatic portosystemic shunt for intractable esophageal-gastric variceal hemorrhage in a patient with idiopathic myelofibrosis. Cardiovasc Intervent Radiol 2000 23 : 491 2.
64. Alvarez-Larran A, Abraldes JG, Cervantes F, Hernandez-Guerra M, Vizzutti F, Miquel R, et al. Portal hypertension secondary to myelofibrosis: a study of three cases. Am J Gastroenterol 2005 100 : 2355 8.
65. Wiest R, Strauch U, Wagner H, Strotzer M, Woenckhaus M, Schroder G, et al. A patient with myelofibrosis complicated by refractory ascites and portal hypertension: to tips or not to tips? A case report with discussion of the mechanism of ascites formation. Scand J Gastroenterol 2004 39 : 389 94.
66. Watanabe H, Shinzawa H, Saito T, Ishibashi M, Shirahata N, Miyano S, et al. Successful emergency treatment with a transjugular intrahepatic portosystemic shunt for life-threatening Budd-Chiari syndrome with portal thrombotic obstruction. Hepatogastroenterology 2000 47 : 839 41.
67. Zahn A, Gotthardt D, Weiss KH, Richter G, Schmidt J, Stremmel W, et al. Budd-Chiari syndrome: long term success via hepatic decompression using transjugular intrahepatic porto-systemic shunt. BMC Gastroenterol 2010 10 : 25.
68. Naqvi T, Baumann MA. Myelofibrosis: response to busulfan after hydroxyurea failure. Int J Clin Pract 2002 56 : 312 3.
69. Petti MC, Latagliata R, Spadea T, Spadea A, Montefusco E, Aloe Spiriti MA, et al. Melphalan treatment in patients with myelofibrosis with myeloid metaplasia. Br J Haematol 2002 116 : 576 81.
70. Tefferi A, Silverstein MN, Li CY. 2-Chlorodeoxyadenosine treatment after splenectomy in patients who have myelofibrosis with myeloid metaplasia. Br J Haematol 1997 99 : 352 7.
71. Tefferi A, Elliot MA, Yoon SY, Li CY, Mesa RA, Call TG, et al. Clinical and bone marrow effects of interferon alfa therapy in myelofibrosis with myeloid metaplasia. Blood 2001 97 : 1896.