Introduction

Article Outline

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For the first time, the word “cure” can be considered a realistic objective in the treatment of patients with chronic lymphocytic leukemia and other types of indolent leukemias and lymphomas. The clinical progress that has led to this possibility is largely related to the availability of active monoclonal antibodies (MABs) and their use in chemoimmunotherapeutic regimens. The identification of prognostic markers that can help stratify patients into clinically meaningful risk groups may help select patients who may benefit from intervention earlier in the course of the disease, resulting in potentially better outcomes. New therapeutic strategies incorporating MABs have been shown to achieve a state of minimal residual disease (MRD) as detected by recently available sensitive technologies. The attainment of minimal residual disease-negative status may prove to be a clinically valuable endpoint because it may predict duration of remission and possibly survival.

The two most prominent MABs for the treatment of lymphoid malignancies are alemtuzumab and rituximab. Rituximab has shown its greatest level of activity in the treatment of previously untreated patients and when combined with chemotherapeutic agents. Alemtuzumab as monotherapy has provided new hope for fludarabine-refractory chronic lymphocytic leukemia patients. Clinical trials have shown the efficacy of alemtuzumab, alone or in combination with chemotherapeutic agents, in this patient population, as outlined by Dr Kanti Rai. Novel uses for alemtuzumab include consolidation therapy, maintenance therapy, and use in patients with p53 mutations. Recent studies have shown that alemtuzumab can eradicate minimal residual disease, as demonstrated by such sensitive methods as polymerase chain reaction and four-color flow cytometry, a topic addressed by Dr Peter Hillmen. Because the safety profile of MABs may differ from that of chemotherapy, Dr Anders Österborg addresses the management of alemtuzumab-related side effects. Alemtuzumab is now being investigated for other novel applications, such as for in vivo purging of stem cells for transplantation and in preventing graft-versus-host-disease during nonmyeloablative hematopoietic transplantation, a topic discussed by Dr Sergio Giralt, and the treatment of T cell malignancies, discussed by Dr Claire Dearden.

We are in the midst of a great revolution in the treatment of chronic lymphocytic leukemia and other leukemias and lymphomas, due in large part to these MABs. This supplement will hopefully provide clinicians with the evidence and information needed to ensure optimal care of their patients and capture the imagination of clinical researchers to develop even more effective treatment strategies.