Leukemia, chronic granulocytic

Hydroxy urea (HU), a hydroxylated derivative of urea, has long been used in the treatment of various forms of neoplastic disorders such as polycythemia vera, head and neck cancer, chronic granulocytic leukemia, and more recently in sickle cell disease, / thalassemia and HIV infection [1],... 

Its primary indications are myeloproliferative disorders, including chronic granulocytic leukemia, polycythemia vera, and essential thrombocytosis. It is also used in combination with radiotherapy for head and neck cancer and for carcinoma of the cervix. Hydroxycarbamide is well absorbed after oral administration. It is in part metabolized in the liver and also excreted unchanged in the urine its elimination half-life is 2-5 hours. Its major toxicity consists of short lasting bone marrow depression. 

Busulfan is used in the palliative treatment of chronic granulocytic leukemia. Daily oral therapy results in decreased peripheral white blood cells and improved symptoms in almost all patients during the chronic phase of the disease. Excessive uric acid production from rapid tumor cell lysis should be prevented by coadministration of allopurinol. 

Hydroxyurea is used for the rapid lowering of blood granulocyte counts in patients with chronic granulocytic leukemia. The drug also can be used as maintenance therapy for patients with the disease who have become resistant to busulfan. Only a small percentage of patients with other malignancies have had even brief remissions induced by hydroxyurea administration. 

Advanced testicular carcinoma Hodgkin s and non-Hodgkin s lymphomas squamous cell carcinoma of head, neck, cervix, skin Prostatic cancer Chronic granulocytic leukemia Testicular and ovarian cancer... 

Ovarian adenocarcinoma, Breast carcinoma, Hodyhin s disease, non-Hodgkin s lymphoma, multiple myeloma, leukemia (acute lymphoblastic, acute myelogenous, acute monocytic, chronic granulocytic, chronic lymphocytic), mycosis fungoides, disseminated neuroblastoma, retinoblastoma PO 1-5 mg/kg/day. IV 40-50 mg/kg in divided doses over 2-5 days or 10-15 mg/kg every 7-10 days or 3-5 mg/kg twice a week. Biopsy-proven minimal-change nephrotic syndrome PO 2 5-3 mg/kg/day for 60-90 days. 

Nowell PC, Hungerford DA. A minute chromosome in human chronic granulocytic leukemia. Science 1960 132 1497. 

Melphalan is an antineoplastic drug, listed also as a Class I immunosuppressive agent (effective only when given prior to the immune stimulus) [1]. It is used for the treatment of multiple myeloma, ovarian carcinoma, tumors of the testes, chronic granulocytic leukemia, chronic lymphocytic leukemia, seminoma, Ewing s sarcoma, reticulum cell sarcoma, and thymoma [1,2]. Its use as an adjuvant to surgery in the management of primary breast cancer was one of the first illustrations of the therapeutic potential of combined modalities of treatment [3]. 

Jolles and Joll s (1984) have reviewed the use of lysozyme as a marker in certain diseases. Serum lysozyme levels have been used extensively in the diagnosis of leukemias. Jolles and Jolles discussed some of the reasons for increased and decreased serum levels in various diseases, such as acute or chronic granulocytic leukemia, myeloid metaplasia, and aplastic anemia, and decreased levels in tears in keratoconjunctivitis. They have also considered the interaction of lysozyme with sulfated proteoglycans and its role in the calcification of epiphyseal cartilage. It is to be expected that such studies will yield valuable information, giving rise to further applications in the future (see also Fett et al., 1985). Lysozyme will continue, of course, to serve as a prototype protein for the investigation of the specificity of immune recognition. 

The presence of greater than normal amounts of thrombocytes in the circulation is known as thrombocytosis and along with reticulocytosis and leukocytosis is a manifestation of increased activity of the hematopoietic system. Zucker and Woodard (Z2) reported a series of 12 patients with thrombocytosis, consisting of two cases of polycythemia vera, three of essential thrombocytemia, three of chronic granulocytic leukemia, one myeloproliferative syndrome, one erythroleukemia, and one cancer of the bladder. The platelet counts ranged from 685 X 10 to 2500 X 10 per cubic millimeter, all much above the upper limit of normal. 

The term myeloproliferative disorders has been applied to all those conditions which are characterized by proliferation of cells in bone marrow or in other sites of extramedullary blood formation. The overgrowth is self-perpetuating and involves one or more lines of bone marrow elements (myelocytic, erythrocytic, megakaryocytic) and cells like fibroblasts derived from the reticulum. We have already mentioned some of these conditions, for example, chronic granulocytic leukemia and myeloid metaplasia, in connection with our discussion on the relationship between serum acid phosphatase and the platelet count. 

Szajd, J., and Pajdak, W., Acid phosphatases of normal and chronic granulocytic leukemia/CGL/leukocytes. Proc. Int. Congr. Int. Soc. HematoL, 12lh, New Yorkp. 35 (1968). Abstr. 

Tefferi A, Grendahl DC. Natural leukocyte interferon-alpha therapy in patients with chronic granulocytic leukemia who have antibody-mediated resistance to treatment with recombinant interferon-alpha. Am J Hematol 1996 52(3) 231-3. 

Cervantes F, Rozman C, Brugues R, Lianas I. Iron stores in chronic granulocytic leukemia at presentation. Scand J Haematol 1984 32 469-74. 

Sokal JE, Sheerin KA. Decreased stainable marrow iron in chronic granulocytic leukemia. Am J Med 1986 81 395-9. 

Excessive uric acid production is consistently seen in untreated chronic granulocytic leukemia patients, but not in those with chronic lymphocytic leukemia (K15, K24, SI). That the increased production of uric acid is a symptom of the disease is shown in a series of patients studied before and after initiation of therapy. When the disease was under control, there was a marked decrease in both serum and urinary uric acid (Table 1). The unusual nature of the high uric acid production and its relationship... 

Uric Acid Excretion in Untreated and Controlled Chronic Granulocytic Leukemia"... 

Fig. 6. Incorporation of formate- C into urinary uric acid of a patient with chronic granulocytic leukemia. [From (K24).]...

C3. Cramer, E., Auclair, C., Hakim, J., Feliu, E., Boucherot, J., Troube, H., Bernard, J.-F., Bergogne, E., and Boivin, P., Metabolic activity of phagocytozing granulocytes in chronic granulocytic leukemia ultrastructural observation of a degranulation defect. Blood 50, 93-106 (1977). 

P2. Pinkerton, P. H., and Robinson, J. B., Granulocyte function in untreated acute and chronic granulocytic leukemia. Acta Haematol. 56, 65-72 (1976). 

Ward, P. A., Disorders of leukocyte function. Annu. J. Pathol. 88, 7(X)-752 (1977). Whittaker, J. A., Khurshid, M., and Hughes, H. R., Neutrophil function in chronic granulocytic leukemia before and after Busulphan treatment. Br. J. Haematol. 28, 541-549 (1974). 

Thioguanine, a purine antimetabolite (2 mg/kg daily p.o.), is indicated in the treatment of acute lymphoblastic and myelogenous leukemia, and chronic granulocytic leukemia. 

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