Rarer chronic lymphoid leukaemias represent a challenge to the clinicians due to 
the limited information on their pathogenesis, difficulties on setting up 
prospective clinical trials and to their refractoriness to drugs used in the 
most common form of chronic lymphocytic leukaemia (CLL). In this review all 
these issues are addressed in three B-cell leukaemias: B-cell prolymphocytic 
leukaemia (B-PLL), hairy cell leukaemia (HCL) and HCL-variant and three T-cell 
leukaemias: T-cell prolymphocytic leukaemia (T-PLL), T-cell large granular 
lymphocytic leukaemia (T-cell LGLL) and adult T-cell leukaemia lymphoma (ATLL). 
Data will be presented on the natural history, current therapies and emerging 
drugs potentially useful in the treatment of patients with these leukaemias. 
Emphasis is made on: 1- the novel agents targeting a variety of B and T-cell 
antigens expressed on the surface of the leukaemic cells; these are either 
unconjugated monoclonal antibodies (McAb) such as Rituximab (anti-CD20), the 
second and third generation of anti-CD20 McAbs, Alemtuzumab (anti-CD52), 
Siplizumab (anti-CD2), Daclizumab (anti-CD25) and KW-0761, an anti-chemokine 
receptor 4 (CCR4) or McAbs conjugated to toxins such as CD22 linked to the 
pseudomonas exotoxin or radiolabelled McAb; 2- the use of new purine nucleosides 
such as nelarabine and 3- agents targeting deregulated genes in the leukaemic 
cells from these diseases such as the Poly (ADP-ribose) polymerase (PARP) 
Olarapib in T-PLL with deregulation of the ataxia telangiectasia mutated (ATM) 
gene. Data of phase I and II clinical studies with these agents as well as the 
potential and current use of other drugs are outlined.