Prolymphocytic leukemia (PLL) is a rare lymphoproliferative disorder characterized by marked leukocytosis and splenomegaly. PLL accounts for approximately 2% of chronic lymphoid leukemias. The clinical course is progressive in the majority of cases due to the resistance of the disease to conventional chemotherapy. The disease is divided according to the cell of origin into the B- (B-PLL) and T-cell (T-PLL) types. T-PLL and B-PLL are morphologically identical, but lymphadenopathy and skin involvement are more common in T-PLL than in B-PLL. Approximately 80% of cases are of B-cell phenotype. T-PLL has a more aggressive course, poorer response to chemotherapy, and shorter median survival than B-PLL. PLL has poorer prognosis than chronic lymphocytic leukemia (CLL), and the patients with static disease for a longer period of time are rare. In general, B-PLL patients have better prognosis than T-PLL patients.
PLL is still considered an incurable disease. Similarly to CLL, treatment is not indicated in asymptomatic patients. In previous decades, splenectomy, splenic irradiation, leucapheresis, and alkylating agents used alone or in combination with other cytotoxic agents have been used for the treatment of PLL. Subsequently, purine nucleoside analogs (fludarabine, cladribine, and pentostatin) have been introduced for the therapy of these disorders. More recently, monoclonal antibodies, especially alemtuzumab, have been found more effective, especially in T-PLL. Finally, high-dose chemotherapy followed by allogenic or autologous stem cell transplantation seems to be an effective, probably curative, strategy for the treatment of selected patients with PLL. In this review, current therapeutic strategies in PLL are presented.

Keywords: Antibodies, Monoclonal - therapeutic use, Antibodies, Monoclonal, Humanized, Antibodies, Monoclonal, Murine-Derived, Antibodies, Neoplasm - therapeutic use, Cladribine - therapeutic use, Drug Therapy - methods, Leukemia, Prolymphocytic - genetics, Pentostatin - therapeutic use, Purine Nucleosides - therapeutic use, Splenectomy - methods, Stem Cell Transplantation - methods, Vidarabine - therapeutic use