Pentostatin

Pentostatin (2'-deoxycoformycin; Nipent), a potent inhibitor of adenosine deaminase, is a purine nucleoside analogue that is highly effective in the treatment of hairy-cell leukemia. This agent is capable of inducing durable complete remissions in the majority of patients, and is capable of re-inducing a complete remission in many of the patients who have relapsed. Pentostatin appears to have changed the natural history of this disease. Long-term follow-up studies suggest that patients with hairy-cell leukemia who are induced into complete remission have a projected survival comparable to age-matched controls. While purine nucleoside analogues induce profound T-cell dysfunction and longstanding immunosuppression, the incidence of secondary malignancies is apparently not increased. Infections still pose a threat to these patients, and effective strategies for treating this disease that do not further compromise the immune system are needed. Patients with this disease should be encouraged to participate in ongoing clinical trials to better define the optimal treatment regimen. New studies should explore the combination of pentostatin and rituxan in treating the typical form of hairy-cell leukemia, and the incorporation of new agents for those with the rare variant form of this disease.

Pentostatin is a nucleoside antibiotics with a strong inhibitory effect on adenosine deaminase, and is widely used in the clinical treatment of malignant tumors. However, the high cost hampers its application. In the past 10 years, the biosynthesis of pentostatin were focused on strain breeding, optimization of medium composition and fermentation process. To date, there are no reviews summarizing the elucidated biosynthetic mechanism of pentostatin. This review starts by introducing the various chemical route for production of pentostatin, followed by summarizing the mechanisms of pentostatin biosynthesis in different microorganisms. Finally, challenges for biosynthesis of pentostatin were discussed, and strategies for regulating and improving the microbial synthesis of pentostatin were proposed.

Major advances in the management of patients who have hairy cell leukemia have been made following the use of purine nucleoside analogs. Pentostatin and cladribine are equally effective, and have impressive long-term effectiveness. Although the degree of myelosuppression may be less with the use of pentostatin, this may reflect differences in the schedule and dose of drug administration between these agents. The gradual, but relentless, improvement in the peripheral blood counts enables out-patient management with pentostatin in most patients. Cladribine affords the convenience of a single course of administration. A direct comparative study with these two agents is unlikely to yield the optimal management of patients who have minimal residual disease following the administration of either agent is warranted in the context of a clinical trial. Patients do relapse, and the overall survival curves have not reached a plateau, which indicates that cure has not been secured. The satisfaction of having improved the outcome for patients who have this previously untreatable leukemia should not give way to complacency for further improvement in the management of this disease. Future studies should be directed to optimizing the therapy for minimal residual disease as well as clearer definition of supportive care.