Objectives: The Italian Society of Hematology (SIE) and two affiliate societies (SIES and GITMO) commissioned a project to develop clinical practice guidelines for the treatment of chronic lymphocytic leukemia (CLL).
Methods: Key questions in the management of patients with CLL were formulated by an Advisory Committee and approved by an Expert Panel of eight senior hematologists. After a systematic review of the literature, recommendations for disease-specific and supportive therapies were formulated and graded according to the supporting evidence. Explicit consensus methods were used for providing recommendations for questions with incomplete or potentially biased evidence.
Results: It is recommended that therapy is commenced in patients with CLL when at least one of the following are present: B-symptoms, progressive/obstructive lymphadenopathy or organomegaly, rapid lymphocyte doubling time, anemia or thrombocytopenia (of new onset, worsening or steroid-resistant). It is recommended that patients without co-morbidity should receive fludarabine plus cyclophosphamide, whereas elderly patients with co-morbidity should receive oral chlorambucil. Younger patients with unfavorable biological risk factors should be considered for high-dose chemotherapy and autologous or allogeneic stem cell transplantation within approved clinical trials. Patients either relapsing rapidly after, or non-responsive to, first-line chlorambucil should receive fludarabine-containing regimens. Patients either relapsing soon after or not responding to fludarabine-based chemotherapy should be considered for schedules including non-cross-reactive agents, such as alemtuzumab, possibly followed by high-dose chemotherapy and autologous transplantation in the context of a clinical trial or by allogeneic stem cell transplantation.
Conclusions: We describe the results of a systematic literature review and an explicit approach to consensus techniques which resulted in recommendations for the key therapeutic decisions in patients with CLL.