Initial Treatment Approach

In the past, treatment decisions regarding the initial therapy for hairy cell leukemia evaluated the merit of a 12-month course of interferon-a versus that of splenectomy. However, the success of 2-chlorodeoxyadenosine (2-CdA; cladribine) and 2'-deoxycoformycin (DCF; pentostatin) has relegated both interferon and splenectomy to be used only in certain uncommon clinical situations.

2-CHLORODEOXYADENOSINE Mechanism of action

Lymphocytes possess high levels of deoxycytidine kinase. Cells low in adenosine deaminase activity accumulate deoxypurine nucleotides, and cell death ensues. This is similar to the situation in severe combined immunodeficiency syndrome, in which one-third of children exhibit an adenosine deaminase deficiency. These observations led to the development of cladrib-ine, or 2-CdA, by Professor Dennis Carson in 1980.2 Cladribine is a purine nucleoside characterized by the substitution of chlorine for hydrogen at position 2 of the purine ring. This substitution confers resistance to cladribine from the action of adenosine deaminase. The high activity of deoxycytidine kinase in lymphocytes, in combination with the resistance to adenosine deaminase, drives the conversion and intracellular accumulation of 2-CdA triphosphate and its subsequent incorporation into the lymphocyte's DNA (see Figure 31.1). Once these nucleotides become incorporated into DNA, strand breakage ensues, leading to cell death. Cladribine is toxic to both resting and dividing lymphocytes, making it a therapeutically attractive candidate in low-grade lymphoproliferative disorders.

Treatment results

The first use of cladribine in the treatment of hairy cell leukemia was published in 1987 by Carrera et al.3 In 1990, investigators at Scripps Clinic in La Jolla reported on 12 patients with hairy cell leukemia treated with a single 7-day course of 2-CdA at a dose of 0.1 mg/kg daily by continuous intravenous infusion; 11 of the 12 patients achieved a complete response (CR), and the remaining patient had a partial response

d-Adertosine

-d-Adenosine"

dAMP

-dADP

dATP

2-CdA

2'-deoxycoformycin dCK

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