Leukemia hairy cell

Hair -wave preparations Hairy cell leukemia Hake... 

Interferons (lENs) (52,53), a family of species-specific vertebrate proteins, confer nonspecific resistance to a broad range of viral infections, affect cell proliferation, and modulate immune responses. AH three principal interferons, a-interferon (lEN-a) produced by blood leucocytes, P-interferon (lEN-P) by fibroblasts, and y-interferon (lEN-y) by lymphocytes, also have antiviral activity. The abiUty of interferons to inhibit growth of transplantable and carcinogen-induced tumor led to research showing the direct antiproliferative and indirect immune-mediated antitumor activities (see Chemotherapeutics, anticancer). IENs have been found to be efficacious in certain malignancies and viral infections, eg, hairy cell leukemia (85% response) and basal cell carcinoma (86% response). However, the interferons do have adverse side effects (54). 

DiaZepin Nucleosides. Four naturally occurring dia2epin nucleosides, coformycin (58), 2 -deoxycoformycin (59), adechlorin or 2 -chloro-2 -deoxycoformycin (60), and adecypenol (61), have been isolated (1—4,174,175). The biosynthesis of (59) and (60) have been reported to proceed from adenosine and C-1 of D-ribose (30,176,177). They are strong inhibitors of adenosine deaminase and AMP deaminase (178). Compound (58) protects adenosine and formycin (12) from deamination by adenosine deaminase. Advanced hairy cell leukemia has shown rapid response to (59) with or without a-or P-interferon treatment (179—187). In addition, (59) affects interleukin-2 production, receptor expression on human T-ceUs, DNA repair synthesis, immunosuppression, natural killer cell activity, and cytokine production (188—194). 

Pentostatin is effective in the treatment of hairy cell leukemia, producing 80-90% remissions (with a complete remission rate of more than 50%). The common side effects of pentostatin include myelosuppression, nausea, and skin rashes. Renal failure,... 

Cladribine is highly active against hairy cell leukemia (complete remssions were achieved in more than 60% of patients receiving a single 7-day course). Activity has been recorded in other low-grade lymphoid malignancies. The major side effect is myelosuppression. 

Interferon alfacon-1 (Inferax ), interferon alfa-2b (IntronA ), and interferon alfa-2a (Roferon -A) are applied in the treatment of chronic hepatitis B and C and some malignancies, especially hairy cell leukemia. IFN-a proteins induce the expression of antiviral, antiproliferative and immunomodulatory genes. 

Lymphosarcoma, severe psoriasis, cancer of the head, neck, breast, lung, rheumatoid arthritis (RA) Alpha-interferon-refractory hairy cell leukemia... 

Intron A interferon a-2b Schering-Plough Hairy cell leukemia, genital warts, AIDS-related Kaposi s sarcoma, hepatitis C, hepatitis B, malignant melanoma, follicular lymphoma in conjunction with chemotherapy... 

Hairy cell leukemia Genital warts AIDS-related Kaposi s sarcoma Non-A non-B hepatitis Hepatitis B Malignant melanoma Chronic viral hepatitis C Follicular lymphoma with chemotherapy June 1986 June 1988 Nov. 1988 Feb. 1991 July 1992 Dec. 1995 March 1997 Nov. 1997... 

Golomb, H.M. et al., Report of a multi-institutional study of 193 patients with hairy cell leukemia treated with interferon-alfa2b, Semin, Oncol., 15, 7, 1988. 

Quesada, J.R. et al., Alpha interferon for induction of remission in hairy-cell leukemia, N. Engl. JMed., 310, 15, 1984. 

Teichmann, J.V. et al., Modulation of immune functions by long-term treatment with recombinant interferon-alpha 2 in a patient with hairy-cell leukemia, J Interferon Res, 8, 15, 1988. 

Interferon Immunomodulator antiviral, hairy cell leukemia Bone marrow suppression granulocytopenia leukopenia... 

Because of its antiviral and anticancer effects, IFN-a is used in the treatment of hepatitis and various forms of cancer, such as Kaposi s sarcoma, non-Hodgkin s lymphoma, and hairy cell leukemia. Exhibit 4.8 describes the treatment of hepatitis C with IFN- . IFN-jS is used for treating multiple sclerosis, a chronic disease of the nervous system. The medical application of IFN-y is for cancer, AIDS, and leprosy. 

Interferon- alpha-la 1986 and later Hairy cell leukemia, Kaposi s sarcoma... 

Interferons (IFN) are glycoproteins that, among other products, are released from virus-infected cells. In neighboring cells, interferon stimulates the production of "antiviral proteins." These inhibit the synthesis of viral proteins by (preferential) destruction of viral DNA or by suppressing its translation. Interferons are not directed against a specific virus, but have a broad spectrum of antiviral action that is, however, species-specific. Thus, interferon for use in humans must be obtained from cells of human origin, such as leukocytes (IFN-a), fibroblasts (IFN-P), or lymphocytes (IFN-y). Interferons are also used to treat certain malignancies and autoimmune disorders (e.g., IFN-a for chronic hepatitis C and hairy cell leukemia IFN-p for severe herpes virus infections and multiple sclerosis). 

HCG human chorionic gonadotropin HCL hairy cell leukemia Hct hematocrit HCTZ hydrochlorothiazide HD hemodialysis HDAC histone deacetylase Hep hepatitis hepatotox hepatotoxicity HER2 type of cancer gene HF heart failure HFA designation for type of inhalation device Hgb hemoglobin HIT/HITTS heparin-mduced thrombocytopenia... 

MLA—Mucose lymphocyte antigen Hairy cell leukemia... 

Cladribine, or 2-chlorodeoxyadenosine, is resistant to adenosine deaminase and after intracellular phosphorylation by deoxycytidine kinase, it is incorporated into DNA. It is considered the drug of choice in hairy cell leukemia because of high activity combined with acceptable toxicity. Cladribine shows variable oral absorbtion and is usually administered intravenously. Its concentration-time course is biphasic with plasma half-lives of 35 minutes and 6.7 hours. Excretion is primarily by the kidneys. Its most prominent dose-limiting toxicity is myelosup-pression. 

Interferon alfa-2b is useful in the treatment of a rare form of chronic leukemia, hairy cell leukemia, in which it produces remissions in 60 to 80% of patients. However, it has minimal antitumor activity in most human cancers. Remissions lasting a few months have been observed in 10 to 20% of patients with lymphomas, multiple myeloma, melanoma, renal cell carcinoma, and ovarian carcinoma. 

E. The discovery that the endogenous proteins known as interferons were capable of containing viral infections led to the hope that they would have many beneficial results, including anticancer activity. Although they are effective in the treatment of hairy cell leukemia and AIDS-associated Kaposi s sarcoma, they have not been shown to be the panacea that was originally envisioned. 

Hairy cell leukemia Interferon alfa-2a-. Subcutaneous, IM Initially, 3 million units/day for 16-24 wk. Maintenance 3 million units 3 times/wk. Do not use 36-million-unit vial. Interferon alfa-2b Subcutaneous, IM 2 million units/m 3 timesAvk. If severe adverse reactions occur, modify dose or temporarily discontinue. 

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