Myeloproliferative Disease Medication
- Author: Haleem J Rasool, MD, FACP; Chief Editor: Emmanuel C Besa, MD more...
The goals of pharmacotherapy are to reduce morbidity and to prevent complications. Medication classes used include interferons, antimetabolites, and tyrosine kinase inhibitors (TKIs).
Interferons are naturally produced proteins with antiviral, antitumor, and immunomodulatory actions. Alpha-, beta-, and gamma-interferons may be given topically, systemically, and intralesionally.
Naturally produced proteins with antiviral, antitumor, and immunomodulatory actions. Alpha-, beta-, and gamma-interferons may be administered topically, systemically, and intralesionally. Interferon alfa is recommended for the initial management of low-risk CML. In low-risk CML, significant numbers of patients achieve hematological and molecular remissions. These patients have prolonged survival.
Antimetabolites inhibit cell growth and proliferation.
Antineoplastic agent provides effective palliative treatment that primarily controls symptoms associated with leukocytosis, thrombocytosis, or hepatosplenomegaly due to MPD. Inhibitor of deoxynucleotide synthesis and DOC for inducing hematologic remission in CML. Less leukemogenic than alkylating agents such as busulfan, melphalan, or chlorambucil. Myelosuppressive effects last a few days to a week and are easier to control than alkylating agents. Busulfan has prolonged marrow suppression and can cause pulmonary fibrosis as well. Can be administered at higher doses in patients with extremely high WBC counts (>300,000) and adjusted accordingly as counts fall and platelet counts drop. Dose can be administered as a single daily dose or divided into 2 or 3 doses at higher dose ranges.
Reduces elevated platelet count in patients with essential thrombocythemia and polycythemia vera.
JAK1/JAK2 kinase inhibitor indicated for treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis. Janus-associated kinases (JAKs) JAK1 and JAK2 mediate the signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function.
Tyrosine kinase inhibitors
These agents inhibit the activity of bcr-abl tyrosine kinase, resulting in decreased proliferation and increased apoptosis in Ph-positive cell lines.
Specifically designed to inhibit tyrosine kinase activity of the bcr-abl kinase in Ph+ leukemic CML cell lines. Used to treat newly diagnosed adult patients with CML or those in blast crisis, accelerated phase, or in chronic phase after failure to interferon alfa therapy. Also indicated to treat pediatric patients with Ph+ chronic phase CML whose disease has recurred after stem cell transplant or who have demonstrated interferon alfa resistance. Well absorbed after oral administration, with maximum concentrations achieved within 2-4 hours. Elimination is primarily in feces in form of metabolites.
Multiple tyrosine kinase inhibitor. Inhibits growth of cell lines overexpressing BCR/ABL. Orphan drug indicated for chronic myeloid leukemia (CML) in individuals resistant to or intolerant of prior therapy (eg, imatinib [Gleevec]). Has been able to overcome imatinib resistance resulting from BCR/ABL kinase domain mutations.
Inhibits BCR/ABL kinase. In vitro, inhibits BCR/ABL –mediated proliferation of murine leukemic cell lines and human cell lines derived from Philadelphia chromosome–positive chronic myeloid leukemia. Under the conditions of the assays, was able to overcome imatinib resistance resulting from BCR/ABL kinase mutations in 32 of 33 mutations tested. In vivo, shown to reduce tumor size in a murine BCR/ABL xenograft model. Indicated for Philadelphia chromosome–positive chronic myeloid leukemia in adults whose disease has progressed or who cannot tolerate other therapies that include imatinib.
O'Brien SG, Guilhot F, Larson RA. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003 Mar 13. 348(11):994-1004. [Medline].
Chaiter Y, Brenner B, Aghai E, Tatarsky I. High incidence of myeloproliferative disorders in Ashkenazi Jews in northern Israel. Leuk Lymphoma. 1992 Jun. 7 (3):251-5. [Medline].
Baxter EJ, Scott LM, Campbell PJ. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005 Mar 19-25. 365(9464):1054-61. [Medline].
James C, Ugo V, Le Couedic JP. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005 Apr 28. 434(7037):1144-8. [Medline].
Ursuleac I, Colita A, Adam T, Jardan C, Ilea A, Coriu D. The concomitant occurrence of JAK2V617F mutation and BCR/ABL transcript with phenotypic expression - an overlapping myeloproliferative disorder or two distinct diseases? - case report. J Med Life. 2013 Mar 15. 6(1):34-7. [Medline]. [Full Text].
Mesa RA, Powell H, Lasho T, Dewald G, McClure R, Tefferi A. JAK2(V617) and leukemic transformation in myelofirbrosis with myeloid metaplasia. Leuk Res. 2006/11. 30 (11):1457-60.
Anand S, Stedham F, Beer P, et al. Effects of the JAK2 mutation on the hematopoietic stem and progenitor compartment in human myeloproliferative neoplasms. Blood. 2011 Jul 7. 118(1):177-81. [Medline].
Pardanani A, Brockman SR, Paternoster SF. FIP1L1-PDGFRA fusion: prevalence and clinicopathologic correlates in 89 consecutive patients with moderate to severe eosinophilia. Blood. 2004 Nov 15. 104(10):3038-45. [Medline]. [Full Text].
Levine RL. Another Piece of the Myeloproliferative Neoplasms Puzzle. N Engl J Med. 2013 Dec 10. [Medline].
Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, et al. Somatic CALR Mutations in Myeloproliferative Neoplasms with Nonmutated JAK2. N Engl J Med. 2013 Dec 10. [Medline].
Nelson R. New Gene Mutation Found in Myeloproliferative Neoplasms. Medscape Medical News. Available at http://www.medscape.com/viewarticle/817704. Accessed: December 16, 2013.
Cancer Facts & Figures 2016. American Cancer Society. Available at http://www.cancer.org/acs/groups/content/@editorial/documents/document/acspc-044552.pdf. Accessed: February 26, 2016.
Johansson P, Kutti J, Andreasson B. Trends in the incidence of chronic Philadelphia chromosome negative (Ph-) myeloproliferative disorders in the city of Goteborg, Sweden, during 1983-99. J Intern Med. 2004 Aug. 256(2):161-5.
Kutti J, Ridell B. Epidemiology of the myeloproliferative disorders: essential thrombocythaemia, polycythaemia vera and idiopathic myelofibrosis. Pathol Biol (Paris). 2001 Mar. 49(2):164-6. [Medline].
Scherber R, Dueck AC, Johansson P, et al. The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF): international prospective validation and reliability trial in 402 patients. Blood. 2011 Jul 14. 118(2):401-8. [Medline].
Donato NJ, Talpaz M. Clinical use of tyrosine kinase inhibitors: therapy for chronic myelogenous leukemia and other cancers. Clin Cancer Res. 2000 Aug. 6(8):2965-6. [Medline].
Bjorkholm M, Derolf AR, Hultcrantz M, et al. Treatment-related risk factors for transformation to acute myeloid leukemia and myelodysplastic syndromes in myeloproliferative neoplasms. J Clin Oncol. 2011 Jun 10. 29(17):2410-5. [Medline]. [Full Text].
Jovanovic JV, Ivey A, Vannucchi AM, Lippert E, Oppliger Leibundgut E, Cassinat B, et al. Establishing optimal quantitative-polymerase chain reaction assays for routine diagnosis and tracking of minimal residual disease in JAK2-V617F-associated myeloproliferative neoplasms: a joint European LeukemiaNet/MPN&MPNr-EuroNet (COST action BM0902) study. Leukemia. 2013 Jul 17. [Medline].
Kaplan ME, Mack K, Goldberg JD. Long-term management of polycythemia vera with hydroxyurea: a progress report. Semin Hematol. 1986 Jul. 23(3):167-71. [Medline].
FDA approves Jakafi to treat patients with a chronic type of bone marrow disease. U.S. Food and Drug Administration. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm425677.htm. December 4, 2014; Accessed: February 26, 2016.
Cervantes F, Correa JG, Hernández-Boluda JC. Alleviating Anemia and Thrombocytopenia in Myelofibrosis Patients. Expert Rev Hematol. 2016 Feb 18. [Medline].
FDA approves first drug to treat a rare bone marrow disease. U.S. Food and Drug Administration. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm280102.htm. November 16, 2011; Accessed: February 26, 2016.
Prasad KN, Manjunath P, Priya L, Sasikumar S. Overcoming the problem of pseudohypoxemia in myeloproliferative disorders: Another trick in the bag. Indian J Crit Care Med. 2012 Oct. 16(4):210-2. [Medline]. [Full Text].
Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, et al. Somatic Mutations of Calreticulin in Myeloproliferative Neoplasms. N Engl J Med. 2013 Dec 10. [Medline].
Kralovics R, Passamonti F, Buser AS. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005 Apr 28. 352(17):1779-90. [Medline].
Levine RL, Wadleigh M, Cools J. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005 Apr. 7(4):387-97. [Medline].
O'Brien S, Tefferi A, Valent P. Chronic myelogenous leukemia and myeloproliferative disease. Hematology (Am Soc Hematol Educ Program). 2004. 146-62.
Staerk J, Kallin A, Demoulin JB. JAK1 and Tyk2 Activation by the Homologous Polycythemia Vera JAK2 V617F Mutation:CROSS-TALK WITH IGF1 RECEPTOR. J Biol Chem. 2005 Dec 23. 280(51):41893-9.
|Chronic myelogenous leukemia||Chronic myelogenous leukemia, BCR/ABL1 positive|
|Polycythemia vera||Polycythemia vera|
|Essential thrombocythemia||Essential thrombocythemia|
|Agnogenic myeloid metaplasia/myelofibrosis||Primary myelofibrosis|
|...||Chronic neutrophilic leukemia, not otherwise specified|
|...||Myeloproliferative neoplasms, unclassifiable|