Cladribine

Cladribine, sold under the brand name Leustatin and Mavenclad among others, is a medication used to treat hairy cell leukemia (HCL, leukemic reticuloendotheliosis), B-cell chronic lymphocytic leukemia and Relapsing-remitting Multiple Sclerosis (RRMS). Its chemical name is 2-chloro-2'-deoxyadenosine (2CdA). Cladribine, sold under the brand name Leustatin and Mavenclad among others, is a medication used to treat hairy cell leukemia (HCL, leukemic reticuloendotheliosis), B-cell chronic lymphocytic leukemia and Relapsing-remitting Multiple Sclerosis (RRMS). Its chemical name is 2-chloro-2'-deoxyadenosine (2CdA). As a purine analog, it is a synthetic chemotherapy agent that targets lymphocytes and selectively suppresses the immune system. Chemically, it mimics the nucleoside adenosine. However, unlike adenosine it is relatively resistant to breakdown by the enzyme adenosine deaminase, which causes it to accumulate in cells and interfere with the cell's ability to process DNA. Cladribine is taken up by cells via a transporter. Once inside a cell cladribine is activated mostly in lymphocytes, when it is triphosphorylated by the enzyme deoxyadenosine kinase (dCK). Various phosphatases dephosphorylate cladribine. Activated, triphosphorylated, cladribine is incorporated into mitochondrial and nuclear DNA, which triggers apoptosis. Non-activated cladribine is removed quickly from all other cells. This means that there is very little non-target cell loss. Cladribine is used for as a first and second-line treatment for symptomatic hairy cell leukemia and for B-cell chronic lymphocytic leukemia and is administered by intravenous or subcutaneous infusion. Since 2017, cladribine is approved as an oral formulation (10 mg tablet) for the treatment of RRMS in Europe, UAE, Argentina, Chile, Canada and Australia. Marketing authorization for RRMS and SPMS in the US was obtained in March 2019. Some investigators have used the parenteral formulation orally to treat patients with HCL. It is important to note that approximately 40% of oral cladribine is bioavailable orally. It used, often in combination with other cytotoxic agents, to treat various kinds of histiocytosis, including Erdheim–Chester disease and Langerhans cell histiocytosis, Cladribine can cause fetal harm when administered to a pregnant woman and is listed by the FDA as Pregnancy Category D; safety and efficacy in children has not been established. Injectable cladribine suppresses the body's ability to make new lymphocytes, natural killer cells and neutrophils (called myelosuppression); data from HCL studies showed that about 70% of people taking the drug had fewer white blood cells and about 30% developed infections and some of those progressed to septic shock; about 40% of people taking the drug had fewer red blood cells and became severely anemic; and about 10% of people had too few platelets. At the dosage used to treat HCL in two clinical trials, 16% of people had rashes and 22% had nausea, the nausea generally did not lead to vomiting. In comparison, in MS, cladribine is associated with a 6% rate of severe lymphocyte suppression (lymphopenia) (levels lower than 50% of normal). Other common side effects include headache (75%), sore throat (56%), common cold-like illness (42%) and nausea (39%)