B- and T-cell subtypes of prolymphocytic leukemia (PLL) are rare, aggressive 
lymphoid malignancies with characteristic morphologic, immunophenotypic, 
cytogenetic, and molecular features. Prognosis for these patients remains poor, 
with short survival times and no curative therapy. The advent of mAbs has 
improved treatment options. In B-PLL, rituximab-based combination 
chemoimmunotherapy is effective in fitter patients. TP53 abnormalities are 
common and, as for chronic lymphocytic leukemia, these patients should generally 
be managed using an alemtuzumab-based therapy. Currently, the best treatment for 
T-PLL is IV alemtuzumab, which has resulted in very high response rates of more 
than 90% when given as frontline treatment and a significant improvement in 
survival. Consolidation of remissions with autologous or allogeneic stem cell 
transplantation further prolongs survival times, and the latter may offer 
potential cure. The role of allogeneic transplantation with nonmyeloablative 
conditioning needs to be explored further in both T- and B-PLL to broaden the 
patient eligibility for what may be a curative treatment.