Hairy cell leukemia, treatment

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,... 

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. 

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. 

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 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. 

A recombinant IFN-P, IFN-pia (Rebif Serono and Avonex Biogen) is produced for commercial use in Chinese hamster ovary (CHO) cells. A synthetic mutant produced in bacteria has a substitution of serine for cysteine at amino acid 17, yielding IFN-pib Betaseron Berlex). Both IFN-pia and IFN-pib are approved by the FDA for treatment of multiple sclerosis (MS) and have shown comparable biological activity (see Section 7.3). In vivo IFN-a2 and IFN-alb show comparable biological activity as well as similar side effects [54,55]. However, IFN-P is eliminated faster, resulting in no detectable serum peak levels [56]. The clinical consequence of this is not known. Objective responses, whether partial or complete tumor regression, have been documented in patients with carcinoma of the breast, hairy-cell leukemia, and non-small-cell lung cancer [57,58]. 

Wiernik, P.H., B. Schwartz, J.P Dutcher, N. Turman, and C. Adinolfi, Successful treatment of hairy cell leukemia with beta-ser interferon. Am J Hematol, 1990. 33(4) 244-8. 

G. Other applications Limited data show possible effectiveness of Infergen in the treatment of persistent genital papillomavirus disease and hematologic improvement in patients with hairy-cell leukemia. 

Indications Treatment of chronic hepatitis C, hairy-cell leukemia and AIDS-related Kaposi s sarcoma, as well as for the treatment of chronic phase, Philadelphia chromosome-positive chronic myelogenous leukemia (CML)... 

Indications Treatment of patients with hairy-cell leukemia, malignant melanoma, follicular non-Hodgkin s lymphoma (NHL), AIDS-related Kaposi s sarcoma, chronic hepatitis C, and the skin disorder, condylomata acuminata... 

IFN-a may be used for the treatment of condylomata acuminata (venereal or genital warts), malignant melanoma, hairy cell leukemia and hepatitis B and C, and other types of cancer including skin, kidney and bone cancers. 

Produced by recombinant DNA technology, IFN-a-2a is used for the treatment of chronic myeloid leukemia, Kaposi sarcoma, lymphoma, hairy cell leukemia, hepatitis B and C and cancer of the skin and kidney. It can only be administered by injection or into the bloodstream, and the most common method is subcutaneous injection. This cytokine can be injected every day however, commonly it is... 

Therapeutic indications a2(A)Interferon is presently approved for the management of hairy cell leukemia. More than 90% of patients treated with a interferon have shown resolution of cytope-nia, reduction in the incidence of serious infection, and reduction in the need for transfusions. Other interferons are being tested in the treatment of various tumors, including squamous cell carcinoma, melanoma, and multiple myeloma, among others. 

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 used in the treatment of certain viral diseases, as well as malignant neoplasias and autoimmune diseases e.g., IFN-a for the treatment of chronic hepatitis C and hairy cell leukemia and IFN-p in severe herpes virus infections and multiple sclerosis. 

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