Gökbuget Nicola, Hoelzer Dieter
J W Goethe University Hospital, Medical Clinic III, Theodor Stern Kai 7, 60590 Frankfurt, Germany.
Best Pract Res Clin Haematol. 2006;19(4):701-13. doi: 10.1016/j.beha.2006.06.008.
In recent decades rapid improvements in the results of treatment of adult acute lymphoblastic leukaemia (ALL) have been achieved. This progress has been based mainly on intensification and optimization of chemotherapy, risk-adapted use of stem-cell transplantation, and improved supportive care. However, results in adult patients are still considerably inferior to those in paediatric ALL, and a barrier to further intensification of chemotherapy appears to have been reached regarding toxicity. More recently, the most significant progress has therefore been achieved by individualized and targeted therapy - for example, treatment with monoclonal antibodies (MoAbs). ALL blast cells express a variety of specific antigens which may serve as targets: e.g. CD19, CD20, CD22, CD33, and CD52. Most experience is available for anti-CD20 (rituximab). In ALL, rituximab is combined with chemotherapy mainly in mature B-ALL and Burkitt's lymphoma, and interim results are very promising. Recently studies with rituximab have also been initiated in B-precursor ALL. Other antibodies would be of interest due to a high rate of antigen (e.g. CD19) expression in ALL, but these are not yet generally available. Clinical application in smaller studies or case reports was reported for anti-CD52 and anti-CD33. Overall it can be stated that MoAb therapy in ALL is a promising treatment approach. Monotherapy with MoAbs in relapsed ALL has also occasionally achieved responses, but greater effects can be expected from combination with chemotherapy and treatment in the state of minimal residual disease. Details of these regimens - required level of antigen expression, timing, schedule, dosage and stage of disease - remain to be defined.
近几十年来，成人急性淋巴细胞白血病（ALL）的治疗效果有了迅速改善。这一进展主要基于化疗的强化和优化、干细胞移植的风险适应性应用以及支持治疗的改善。然而，成人患者的治疗结果仍远低于儿童ALL患者，而且在毒性方面似乎已经达到了进一步强化化疗的障碍。因此，最近最重要的进展是通过个体化和靶向治疗取得的——例如，用单克隆抗体（MoAbs）进行治疗。ALL原始细胞表达多种可作为靶点的特异性抗原：例如CD19、CD20、CD22、CD33和CD52。抗CD20（利妥昔单抗）的经验最为丰富。在ALL中，利妥昔单抗主要与化疗联合用于成熟B-ALL和伯基特淋巴瘤，中期结果非常有前景。最近，针对前体B-ALL也开展了利妥昔单抗的研究。由于ALL中抗原（如CD19）的高表达率，其他抗体也很有意义，但目前尚未普遍应用。抗CD52和抗CD33在较小规模研究或病例报告中有临床应用报道。总体而言，可以说ALL中的MoAb治疗是一种有前景的治疗方法。MoAbs单药治疗复发ALL偶尔也能取得反应，但与化疗联合以及在微小残留病状态下治疗可能会有更大效果。这些治疗方案的细节——所需的抗原表达水平、时机、疗程、剂量和疾病分期——仍有待确定。
