Chronic myelocytic leukemia

Hydroxyurea is an oral drug that inhibits ribonucleotide reductase, which converts ribonucleotides into the deoxyribuon-cleotides used in DNA synthesis and repair. The time to peak concentrations of hydroxyurea is 1 to 2 hours after oral administration. Approximately 50% is degraded by the liver to form urea and respiratory carbon dioxide. The remainder is excreted by the kidney. The half-life ranges from 3.5 to 4.5 hours. Hydroxyurea has shown clinical activity in the treatment of chronic myelocytic leukemia, polycythemia vera, and thrombocytosis. The major side effects are myelo-suppression, nausea and vomiting, diarrhea, and constipation. Rash, mucositis, and renal tubular dysfunction occur rarely. 

Kinases Abl kinase Mouse cDNA Cancer, acute lymphocytic leukemia, chronic myelocytic leukemia, chronic neutrophilic leukemia Regulation of cytoskeletal organization and movement... 

Imatinib caused a revolution in the treatment of chronic myelocytic leukemia... 

II. Israels, L. G., Delory, G. E., Hnatiuk, L., and Friesen, E., Studies on the etiology of the elevated serum isomerase in chronic myelocytic leukemia. Blood 13, 78-84 (1958). 

An oxime derivative of indirubin (a natural bis-indole alkaloid used in traditional Chinese medicine to treat chronic myelocytic leukemia), indirubin-3 -monoxime (37), was found to be a potent inhibitor of cyclin-dependent kinases (CDKs), and of the proliferation of myeloid leukemia cells via inhibition of a tyrosine kinase . The 3D structure of the complex of 37 with CDK revealed that the oxime function is intact, and that it occupies the ATP-ribose site of the CDK-ATP structure. While the specific role of the oxime group in the biological activity of 37 is not clear, it was proposed that its reactivity may be utilized for further drug design... 

Chronic myelocytic leukemia (CML) Interferon alfa-2a-. Subcutaneous, IM 9 million units daily. 

Treatment of bladder, cervical, renal carcinoma, chronic myelocytic leukemia, laryngeal papillomatosis, multiple myeloma, mycosis fungoides... 

Lee, L.S. Cheng, Y.C. Human thymidylate kinase. Purification, characterization, and kinetic behavior of the thymidylate kinase derived from chronic myelocytic leukemia. J. Biol. Chem., 252, 5686-5691 (1977)... 

Colchicine is a poisonous tricyclic tropane alkaloid from the autumn crocus (Colchicum autumnale) and gloriosa lily (Gloriosa superba). This alkaloid is a potent spindle fiber poison, preventing tubulin polymerization.25 Colchicine has been used as an effective anti-inflammatory drug in the treatment of gout and chronic myelocytic leukemia, but therapeutic effects are attainable at toxic or near toxic dosages. For this reason, colchicine and its analogs are primarily used as biochemical tools in the mechanistic study of new mitotic inhibitors. 

Busulfan Myleran Chronic myelocytic leukemia Blood disorders (anemia, leukopenia, thrombocytopenia] metabolic disorders (hyperuricemia, fatigue, weight loss, other symptoms]... 

Cyclophosphamide Cytoxan, Neosar Acute and chronic lymphocytic leukemia acute and chronic myelocytic leukemia carcinoma of ovary, breast Hodgkin disease non-Hodgkin lymphomas multiple myeloma Blood disorders (anemia, leukopenia, thrombocytopenia] Gl distress (nausea, vomiting, loss of appetite] bladder irritation hair loss car-diotoxicity pulmonary toxicity... 

Drug(s) Biologic response modifiers Interferons Interferon alfa-2a [Roferon-A] Interferon alfa-2b [Intron-A] Primary Antineoplastic Indication(s) Hairy-cell leukemia Kaposi sarcoma chronic myelocytic leukemia renal and bladder cancers Common Adverse Effects Flulike syndrome [mild fever, chills, malaise]... 

The alkyl sulfonate busulfan (Myleran) is metabolized to an alkylating agent. Because it produces selective myelosuppression, it is used in cases of chronic myelocytic leukemia. It causes pronounced hyperuricemia stemming from the catabolism of purine. 

Harringtonine appears to be the most effective agent and recent studies in the People s Republic of China have shown that it is effective against L615 leukemia, L7212 leukemia, sarcoma 180, and Walker carcinosarcoma 256 (188). Harringtonine also appeared to be effective in the treatment of acute and chronic myelocytic leukemia in humans (189). 

Defective nitrovasodilator-stimulated protein phosphorylation and calcium regulation in cGM P-dependent protein kinase-defident human platelets of chronic myelocytic leukemia. Biol. 

Cholestatic hepatitis occurred in a 61-year-old man with chronic myelocytic leukemia who had taken busulfan for 8 years (27). He presented with fever, abdominal pain, and raised liver enzymes. A liver biopsy showed cellular cholestasis with focal liver cell necrosis accompanied by a mild inflammatory infiltrate. When busulfan was withdrawn, his Uver enzymes normalized and his fever resolved. 

Krug K, Stenzel L. Verlaufsvarianten von Panzytopenien nach Busulfanbehandlung der chronischen myeloischen Leukamie (CML). [Varying course of pancytopenia after busulfan treatment of chronic myelocytic leukemia (CML).] Folia Haematol Int Mag Klin Morphol Blutforsch 1978 105(2) 181-7. 

Honda K, Ando A, Endo M, Shimizu K, Higashihara M, Nitta K, Nihei H. Thrombotic microangiopathy associated with alpha-interferon therapy for chronic myelocytic leukemia. Am J Kidney Dis 1997 30(l) 123-30. 

Fujishita M, Tamura A, Yamada M, Uemura Y, Niiya K, Yoshimoto S, Kubonishi I, Taguchi H, Yoshino T, Ohtsuki Y, et al. [Quadriplegia and cranial nerve palsy during treatment by vincristine in blastic crisis of chronic myelocytic leukemia report of an autopsy case.] Rrnsho Ketsueki 1986 27(8) 1437-42. 

Hydroxyurea is active against melanoma, chronic myelocytic leukemia, and metastatic ovarian carcinoma. It is used in combination with radiotherapy for head and neck cancer. The main toxieity is bone marrow depression expressed as leukopenia anemia, and. iK-casionally. thrombocytopenia. Gastrointestinal toxicity and dermatological reactioas also... 

Imatinib is indicated for chronic myelocytic leukemia. Il acts by inhibiting the tyro.sine kina.se BRC-ABL. thus ptc-venting it from arresting apoptosis. This agent is well ab-.sorbed orally, and the maximum concentration in blood r achieved within 2 to 4 hours. Il is 95% bound to. senim proteins. The major metabolite results from N-demelh l-alion. Elimination half-times are 18 hours for imatinib anl 40 hours for the N-demelhyl metabolite. Excretion is mainly in feces. 

Sodium Phosphate P 32. Sodium phosphate P 32. sodium radiophosphate, is supplied as an aqueous solution of a mixture of NaH2 P04 and Na2H P04 with a pH range ofS.O to 6.0. It contains S mCi/vial (0.67 mCi/mL) of radio-xtivity. expressed as a pure /3-emitter with a half-life of 14.3 days. Sodium phosphate P 32 is indicated for treatment of polycythemia vera. chronic myelocytic leukemia, and CLL Depression of leukocytes and platelets requires monitoring of blood and bone marrow at regular intervals. 

Ghanei M, Vosoghi AA. An epidemiologic study to screen for chronic myelocytic leukemia in war victims exposed to mustard gas. Environ. Health Perspect. 2002 110 519-521. 

Hydroxyurea, an antimetabolite with antineoplastic properties (60 to 80 mg/kg p.o. for a minimum of six weeks), is used in the treatment of melanoma chronic myelocytic leukemia recurrent, metastatic, or inoperable ovarian cancer squamous cell carcinoma of the head and neck polycythemia vera and essential thrombocytosis (see also Figure 15). 

Pipobroman, an alkylating agent with antineoplastic properties, is indicated in the treatment of polycythemia vera and chronic myelocytic leukemia (see also Figme 15). 

Sodium phosphate P 32 is a radiopharmaceutical. Phosphorus is necessary to the metabolic and proliferative activity of cells. Radioactive phosphorus concentrates to a very high degree in rapidly proliferating tissue. Sodium phosphate P 32 decays by beta emission with a physical half-life of 14.3 days. The mean energy of the sodium phosphate P 32 beta particle is 695 keV. It is indicated in the treatment of polycythemia vera, chronic myelocytic leukemia, and chronic lymphocytic leukemia and skeletal metastases. 

---