Purine analog toxicity in patients with hairy cell leukemia

The introduction of cladribine and pentostatin for the treatment of hairy cell leukemia (HCL) has dramatically altered the natural history of the disease, and a single course of cladribine given as a subcutaneous injection for 7 days induces complete remission in the majority of patients. A systematic evaluation of the immediate and long-term side effects induced by purine analogs reveals that most of the available information relates to fludarabine, and mostly refers to the use of this agent in the treatment of indolent lymphoproliferative disorders (LPDs) and and chronic lymphocytic leukemia (CLL). Surprisingly, although purine analogs have been used for more than 30 years in the treatment of HCL, there are still not many reports on the toxicity of pentostatin and cladribine other than the early therapy-induced toxicity encountered in the initial management of patients. Only a few studies have evaluated the long-term adverse effects of purine analogs on the immune system or stem cell toxicity, and most of these are not very recent. In addition, the issue of the prevalence of secondary malignancy linked with the therapy of HCL still remains controversial. In this review the available data on cladribine and pentostatin toxicity in the treatment of HCL are summarized, emphasizing immune suppression, stem cell toxicity, and possible correlation with the development of second malignancy. Other rare toxicities are also described, and the special conditions that need to be taken into account when starting treatment for patients with HCL are also considered.