Pentostatin in prolymphocytic leukemia: phase II trial of the European Organization for Research and Treatment of Cancer Leukemia Cooperative Study Group.
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.


OBJECTIVE
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.


CONCLUSIONS
DCF is active in prolymphocytic leukemia, even as salvage therapy in patients who had received multiple prior chemotherapeutic regimens.


CONCLUSIONS
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.
Döhner
H
H
Medizinische Klinik, University of Heidelberg, Federal Republic of Germany.
Ho
A D
AD
Thaler
J
J
Stryckmans
P
P
Sonneveld
P
P
de Witte
T
T
Lechner
K
K
Lauria
F
F
Bödewadt-Radzun
S
S
Suciu
S
S
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D015448:Leukemia, B-Cell / Q000188:drug therapy; D015463:Leukemia, Prolymphocytic / Q000188:drug therapy*; D015458:Leukemia, T-Cell / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D015649:Pentostatin / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D012074:Remission Induction; D016896:Treatment Outcome
D015649:Pentostatin