Recent Clinical Trials of Cladribine in Hematological Malignancies and Autoimmune Disorders

Abstract

The purine nucleoside analog - cladribine (2-chlorodeoxyadenosine, 2-CdA) is a cytotoxic agent with high activity in lymphoid and myeloid malignancies. It is also an effective drug in some autoimmune disorders. 2-CdA is usually administered intravenously in continuous or 2-hour infusion. Recently however, new formulation of this agent has been developed for subcutaneous and oral administration. 2-CdA is widely established as first line standard treatment for hairy cell leukemia. Moreover several clinical trials have demonstrated that this agent, used alone or in combination with other cytotoxic drugs, showed good efficacy and acceptable toxicity profile in the treatment of chronic lymphocytic leukemia, Waldenström macroglobulinemia, low-grade non-Hodgkin's lymphoma and acute myeloid leukemia. Moreover, some studies indicate that 2-CdA has some activity in progressive multiple sclerosis and other autoimmune disorders including autoimmune hemolytic anemia, rheumatoid arthritis, systemic lupus erythematosus, psoriasis and in patients with refractory factor VIII inhibitors. This review article will summarize the results of recent clinical trials with 2-CdA in hematological malignancies, multiple sclerosis and other autoimmune diseases.

In vitro Response of Human Pathological Hematopoietic Cells to Cladribine

“…Cladribine has established clinical activity in hematological malignancies (DELANNOY 1996;ROBAK 2003;PARKER et al 2004;GREYZ & SAVEN 2004;ROBAK et al 2005ROBAK et al , 2006aROBAK et al , 2006bROBAK et al , 2006c. Nevertheless, some aspects of the action of cladribine are as yet unclear.…”

Bone marrow CFU-GM and human tumor xenograft efficacy of three antitumor nucleoside analogs

“…These compounds are rationally designed prodrugs that avoid metabolic inactivation by adenosine deaminase and retain substrate specificity for deoxycytidine kinase. Intracellular levels of deoxycytidine kinase are one major determinant of the selectivity of these compounds for indolent lymphoid malignancies such as hairy cell leukemia and B-cell chronic lymphocytic leukemia (B-CLL) (20)(21)(22)(23) + T-cells. The expression of deoxycytidine kinase in these normal cells is as high as or higher than the expression in some leukemias and lymphomas.…”

Management del paziente con diarrea, nausea e vomito, malnutrizione e malattia celiaca: lo stato dell'arte

“…In realtà, la cladribina (2-clorodeossiadenosina) (2-A), una purina sintetica con nucleoside omologo, eserciterebbe il suo effetto citostatico inibendo la proliferazione e la divisione delle cellule linfoidi. 145 Pertanto tale farmaco particolarmente attivo contro quelle forme maligne a basso grado di proliferazione, come la leucemia a cellule capellute, potrebbero essere efficaci anche nel trattamento delle forma di MCR di tipo 2. 145 La Tabella 9 elenca le raccomandazioni per la MCR.…”

“…145 Pertanto tale farmaco particolarmente attivo contro quelle forme maligne a basso grado di proliferazione, come la leucemia a cellule capellute, potrebbero essere efficaci anche nel trattamento delle forma di MCR di tipo 2. 145 La Tabella 9 elenca le raccomandazioni per la MCR.…”