Other secondary sequelae of treatments for myeloproliferative disorders.
Polycythemia vera (PV) and essential thrombocythemia (ET) are chronic disorders for which there are no medical cures. Clinical sequelae of PV and ET fall into three categories: primary, such as thrombosis and hemorrhage; secondary, resulting from disease progression or treatment. The decision whether to treat the patient is based on the sequelae of no treatment versus short- and long-term toxicities of the three classes of drugs available for treatment: hydroxyurea, interferon-alpha, and anagrelide. Thrombosis is the most common short-term sequelae of untreated disease; the risk increases with age and after the first thrombotic complication. Hydroxyurea, a nonalkylating myelosuppressive agent, is mutagenic and probably leukemogenic over 5 to 15 years, which makes it unsuitable for treating most younger patients. Interferon-alpha, a cytokine that is myelosuppressive and immunomodulatory, has been shown to have a therapeutic effect in both PV and ET. Tolerance to the initial flu-like symptoms of interferon-alpha is usually developed, but dose-limiting symptoms of anorexia, asthenia, and neuropsychiatric disease can occur, along with exacerbation or development of autoimmune diseases. Anagrelide, a quinazoline that inhibits cyclic nucleotide phosphodiesterase, inhibits platelet aggregation and has an idiosyncratic effect of inhibiting megakaryocyte maturation and platelet budding at doses below those that affect platelet function. This agent is a vasodilator with positive inotropic activity and a side-effect profile that may include palpitations, forceful heartbeat, tachycardia, and headache. One in four patients develop fluid retention and/or edema that are controllable with diuretic therapy. Dizziness is frequent, but mild. Because these side effects usually abate in 2 to 4 weeks, successful management of patients taking anagrelide depends on encouraging them to maintain therapy. The availability of these three classes of drugs with differing modes of action suggests that combination therapy may offer the opportunity to achieve better control of proliferation while reducing short-term side effects as well as the risks of dose-related cumulative sequelae.
Gilbert
Harriet S
HS
Albert Einstein College of Medicine, Bronx, NY, USA.
D000970:Antineoplastic Agents / Q000627:therapeutic use; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D007155:Immunologic Factors / Q000627:therapeutic use; D016898:Interferon-alpha / Q000627:therapeutic use; D019384:Nucleic Acid Synthesis Inhibitors / Q000627:therapeutic use; D011086:Polycythemia / Q000188:drug therapy* / Q000503:physiopathology; D011799:Quinazolines / Q000627:therapeutic use; D013922:Thrombocytosis / Q000188:drug therapy* / Q000503:physiopathology
D000970:Antineoplastic Agents; D005343:Fibrinolytic Agents; D007155:Immunologic Factors; D016898:Interferon-alpha; D019384:Nucleic Acid Synthesis Inhibitors; D011799:Quinazolines; C021139:anagrelide; D006918:Hydroxyurea