New nucleoside analogs for patients with hematological malignancies

In the last few years, several new purine and pyrimidine nucleoside analogs have been synthesized and made available for both preclinical studies and clinical trials.

This article summarizes recent achievements in the mechanism of action, pharmacological properties and clinical activity and toxicity as well as the emerging role of newer purine and pyrimidine nucleoside analogs potentially active in lymphoid and myeloid malignancies. A literature review was conducted from the MEDLINE database PubMed for articles in English. Publications from 2000 to October 2010 were scrutinized. The search terms used were clofarabine, nelarabine, forodesine, 8-chloroadenosine, LMP-420, azacitidine, decitabine, sapacitabine, troxacitabine, thiarabine and zebularine in conjunction with hematologic malignancies, leukemia and lymphoma. Conference proceedings from the previous 5 years of the American Society of Hematology, European Hematology Association, and American Society of Clinical Oncology were searched manually. Additional relevant publications were obtained by reviewing the references from the chosen articles.

Several new nucleoside analogs are currently under investigation in preclinical and clinical studies concerning hematological malignancies. Clofarabine, nelarabine, azacitidine and decitabine have been recently approved for the treatment of leukemias and/or myelodysplastic syndromes. Other agents including forodesine, 8-chloroadenosine, LMP-420, sapacitabine, troxacitabine, thiarabine and zebularine seem to be promising for the treatment of lymphoid and myeloid malignancies. However, definitive data from ongoing and future clinical trials will aid in better defining their status in the treatment of hematological disorders.