Pentostatine Is a Safe and Active Agent in Chronic Lymphocytic Leukemia CLL with Minimal Toxicity.

Abstract

Pentostatin is a nucleoside analogue, it is a potent irreversible inhibitor of adenosine diaminase ADA. The triphosphate form of pentostatin is incorporated into DNA strand breaks. This effect is potentiated by the presence of an alkylating agent such as Cytoxan. Combination approaches will maximize the inhibition of DNA repair with less myelosuppression. A total of twenty five patients diagnosed with chronic lymphocytic leukmia treated with pentostatin combination in the last four years, nineteen patients had refractory CLL. Six patients has newely diagnosis with adverse features such as high risk cytogenetic/FISH abnormality, elevated serum Beta 2 microglobuline, elevated LDH, presence of the B symptoms, doubling time less than a year and progressive enlargment of spleen and lymph nodes. All patients had stage III-IV Rai classification. Fifteen males and ten females, eighty five percent were african american. Mean age is 52 years (range 46–70). Median follow up was eighteen months (range4–42 months). Thirteen patients recieved the combination of Pentostatin, Cytoxan and Rituxan. Rituxan or Rituximab is a chiemeric human monoclonal antibodies against CD expressing B cell lymphocytes. Pentostatin 4 mg/M2, Cytoxan 300 mg/M2 and Rituxan 375 mg/M2 given one day one every 28 days. Three patients recieved pentostatin and cytoxan. Nine patients recieved pentostatin and rituxan. Eighty percent of the patients recieved a minimum of six cycles. Complete response CR and near complete response nCR were confirmed by peripheral blood flowcytometric study. Ten patients achieved CR, nCR and fifteen patients achieved PR. One patient had short PR response less than six months post completing therapy. Five patients had autologous bone marrow transplant post CR, nCR response. Median time to progression is not reached. Toxicity observed with pentostain combination was minimal as compaired to retrospective analysis of Fludarabin whether as a single agent or in combination with cytoxan or rituxan. Bone marrow necrosis and tumor lysis syndrome were not seen. Neutropenic fever that required hospitaliztion is less than 10% as compaired to Fludarabin 40%. Growth factor G-CSF required less with pentostin combination. However, warm autoimmune hemolytic anemia was seen more during pentostatin therapy rather than prior to initiating therapy.Conclusion: Pentostatin has less myelosuppressive effect and equal response as compaired retrospectively to Fludarabine. Head to head randomized prospective study is needed.