Skip to Main Content

++

INTRODUCTION

++

Chronic lymphocytic leukaemia (CLL) is the most common form of leukaemia in adults in the Western world. Conventionally, the mainstays of therapy for CLL have been the alkylating agents, such as chlorambucil and cyclophosphamide, and purine analogues, such as fludarabine and cladrabine. Although the overall response rates (ORR) to these therapies are reasonably high, it is unusual to obtain complete remissions (CR; up to 10% with chlorambucil and 25% with single-agent fludarabine) [1]. In studies comparing fludarabine with chlorambucil, a prolongation in survival has not been observed despite the better response rates seen with fludarabine. There are several reasons for this apparent failure to prolong survival in randomised trials of purine analogues compared to alkylating agents: (1) when patients are randomised between chlorambucil and fludarabine the actual question being addressed is whether fludarabine as first-line therapy is better than fludarabine as second-line therapy because almost a half of patients (46% in the largest study reported [1]) who fail or relapse after chlorambucil will respond to second-line fludarabine; (2) the majority of the responses to fludarabine monotherapy are partial remissions; and (3) the National Cancer Institute (NCI) response criteria which were published in 1996 [2] have a relatively liberal definition of CR (Table 15.1) in that patients achieving a CR can have up to 5% CLL cells in the marrow when sensitive detection methods are applied. The lack of improved overall survival in these studies and the availability of newer therapeutic approaches, such as monoclonal antibodies alone (alemtuzumab) or in combination (rituximab or alemtuzumab), stem cell transplantation (SCT; reduced intensity conditioning allogeneic transplantation or autologous transplantation) and combination chemotherapies (such as fludarabine, cyclophosphamide and mitoxantrone; FCM) has been the stimulus for the development of sensitive assays to minimal residual disease (MRD) in CLL. These assays can detect extremely low levels of CLL (down to a single CLL cell in 100,000 leucocytes) which can be routinely used to improve the depth of remission obtained with these newer therapeutic approaches [3]. The eradication of detectable MRD is possible in a significant proportion of patients with CLL but such intensification of therapy carries with it an increased risk of treatment-related toxicity.

++
Table Graphic Jump Location
Table 15.1***Definition of a complete remission by National Cancer Institute-criteria
++

It is ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.