BACKGROUND: B-cell prolymphocytic leukemias or T-cell prolymphocytic leukemias 
are aggressive variants of chronic lymphoid leukemias. The small studies 
conducted to date have shown median survival durations of approximately 3 years 
for patients who have B-cell prolymphocytic leukemia and 7.5 months for those 
who have T-cell prolymphocytic leukemia, compared with about 8 years for 
patients who have chronic lymphocytic leukemia. In chronic lymphocytic leukemia, 
chemotherapy consisting of alkylating agents such as cyclophosphamide and 
chlorambucil combined with prednisone has achieved overall response rates of 50% 
to 70%, but this regimen has resulted in response rates of less than 25% in 
prolymphocytic leukemia. Pentostatin (2'-deoxycoformycin; DCF) is a purine 
analogue that has shown activity in treatment of chronic lymphoid malignancies.
PURPOSE: This prospective phase II trial by the Leukemia Cooperative Group of 
the European Organization for Research and Treatment of Cancer was performed to 
assess the activity and toxicity of DCF in prolymphocytic leukemia.
METHODS: Twenty patients with B-cell or T-cell prolymphocytic leukemia were 
given DCF at a dosage of 4 mg/m2 intravenously once a week for 3 weeks, then 
every other week for three doses. Patients who had at least partial response 
received maintenance therapy once a month for a maximum of 6 months. Fourteen 
patients had B-cell prolymphocytic leukemia, and six had T-cell prolymphocytic 
leukemia, as evidenced by morphologic and immunologic criteria; three were 
previously untreated, eight had been given one or two chemotherapeutic regimens, 
and nine had been given more than two.
RESULTS: One patient died of an unknown cause during the first 6 weeks of 
treatment, and one died of disseminated toxoplasmosis during the period of 
maintenance therapy, 5 months after achieving partial remission. Nine (45% 
response rate) of the 20 patients achieved partial remission, including seven 
(50%) of 14 with B-cell prolymphocytic leukemia and two (33%) of six with T-cell 
prolymphocytic leukemia. The median duration of response was 9 months (range, 
2-30 months); for patients with B-cell prolymphocytic leukemia, the median 
remission duration was 12 months. No complete remission was observed. Toxic 
effects included nausea and vomiting (30%), infections (30%), and transient 
increase in liver enzymes (35%) and in creatinine (20%) levels. Eight patients 
experienced thrombocytopenia, the major hematologic toxic effect; four had grade 
3 or 4 toxic effects.
CONCLUSION: DCF is active in prolymphocytic leukemia, even as salvage therapy in 
patients who had received multiple prior chemotherapeutic regimens.
IMPLICATIONS: Trials using DCF or other purine analogues alone or in combination 
with standard chemotherapeutic agents in front-line or salvage therapy are 
warranted to improve the prognosis of patients with prolymphocytic leukemia.