Prolymphocytic leukemia is a rare chronic lymphoproliferative disorder that 
includes two subtypes, B cell and T cell, each with its own distinct clinical, 
laboratory and pathological features. T-cell prolymphocytic leukemia has an 
aggressive course with short median survival and poor response to chemotherapy. 
With the use of the purine analogue pentostatin more than half of patients will 
have a major response and a minority will have a complete remission, usually 
lasting months. With the introduction of alemtuzumab, most patients who 
progressed despite treatment with pentostatin had a major response with a 
complete remission rate higher than that obtained with pentostatin when used as 
a first line. Unfortunately, progression still follows shortly. We recommend 
alemtuzumab as initial therapy and offer stem cell transplant (SCT) to selected 
young, healthy patients who respond. Although B-cell prolymphocytic leukemia is 
also a progressive disease, some patients can achieve a prolonged 
progression-free-survival with fludarabine. Patients presenting with massive 
splenomegaly may be effectively palliated with splenic irradiation or 
splenectomy. Rituximab is a promising agent and further investigations are 
warranted to better define its role in treatment of this disorder.