A systematic overview of chemotherapy effects in B-cell chronic lymphocytic leukaemia

A systematic review of chemotherapy trials in several tumour types was perf ormed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scientific literature are describ ed separately (Acra Oncol 2001; 40: 155-65). This synthesis of the literatu re on chemotherapy for B-cell chronic lymphocytic leukaemia (B-CLL) is base d on data from 20 randomised controlled trials and one meta-analysis. Moreo ver. data from 19 prospective studies. one retrospective study and four oth er articles were used. Totally 44 scientific articles are included. involvi ng 11 289 patients. The conclusions reached can be summarized into the foll owing points: Primary treatment of patients with symptomatic B-CLL is recommended to be a n oral alkylating agent such as chlorambucil. This drug induces tumour remi ssion and symptomatic relief in a majority of patients with progressive dis ease. Response may be long-lasting, but cure is not obtained. Optimum dose and schedule of administration of chlorambucil or other alkylating agents h ave not been defined. It is recommended to defer initial therapy until required by disease progre ssion. Large randomised trials have demonstrated that early treatment with chlorambucil in a continuous or an intermittent schedule does not prolong s urvival in B-CLL patients with low tumour burden (Binet stage A). The addition of corticosteroids to alkylator regimens has not been proven t o give any benefit. Combination chemotherapy as primary treatment has not shown any advantage c ompared with single drugs. Early inclusion of anthracyclines to the therapy does not convincingly add to the activity of alkylating agents. The purine analogues fludarabine and 2-chlorodeoxyadenosine are active in B -CLL. However, like other drugs, they do not appear to be curative. In rand omised multicentre trials a benefit from fludarabine as primary therapy com pared with polychemotherapy (CHOP or CAP) has been observed in terms of tol erance and treatment response but not yet in survival. No randomised studie s have been performed to show whether one of the purine analogues should be preferred. At relapse after single drug treatment. retreatment with the same drug ofte n induces new remissions. However. the proportion of patients responding de clines each time chlorambucil or any other single agent is readministered. At progression on single alkylating agents. the purine analogues or various combinations. mostly CHOP. frequently induce tumour remissions. For patients with advanced B-CLL failing to respond to fludarabine or CHOP. the prognosis is poor. None of the salvage regimens reported has produced durable remissions. High-dose chemo-radiotherapy with stem cell transplantation has been evalua ted for young patients with B-CLL. A long survival has been shown in some p atients following allogeneic and autologous transplantation. However. the r isk of transplantation-related mortality is still high with allo-transplant s and relapse is common after auto-transplantation. A benefit of purging au tologous stem cells has been proposed but evidence is lacking. Thus. transp lantation remains experimental: more patients and a longer follow-up are ne eded to assess if cure can be achieved. In the future an individual risk-adapted therapy will be required. The clin ical heterogeneity of the disease has pointed to the necessity of new predi ctors for prognosis evaluated in prospective trials.