Osterborg Anders, Karlsson Claes, Lundin Jeanette, Kimby Eva, Mellstedt Håkan
Department of Oncology and Hematology, Karolinska University Hospital, Stockholm, Sweden.
Semin Oncol. 2006 Apr;33(2 Suppl 5):S29-35. doi: 10.1053/j.seminoncol.2006.01.027.
B-cell chronic lymphocytic leukemia has traditionally been treated with alkylating agents and purine analogues. The introduction of alemtuzumab, a CD52 monoclonal antibody with significant clinical activity in chemotherapy refractory B-cell chronic lymphocytic leukemia, is accompanied by a side effect profile different from that resulting from chemotherapy. The intravenous administration of alemtuzumab is usually accompanied by transient infusion-related side effects manifesting primarily as flu-like symptoms. These reactions can be reduced by use of corticosteroid prophylaxis, and will subside gradually during continued treatment. Alternatively, administration of alemtuzumab subcutaneously may markedly reduce the occurrence of general side effects but results in limited transient local skin reactions in most patients. Neutropenia (grade 4) may occur in approximately 20% of patients, but is usually transient and/or responds promptly to colony stimulating factor therapy; episodes of febrile neutropenia are infrequent. The major side effect of alemtuzumab is T-cell depletion, leading to an increased risk of infection, in particular reactivation of cytomegalovirus. This event typically occurs 3 to 8 weeks after initiation of therapy, coinciding with the T-cell nadir. With vigilance and early detection, these infections are usually manageable and do not cause organ failure. Preliminary data indicate that other infections following alemtuzumab therapy do not seem to occur at a frequency that is higher than expected, probably because of the general prophylactic use of cotrimoxazole (trimethoprim and sulfamethoxazole) and valacyclovir in combination with clinical tumor regressions. The overall safety profile of alemtuzumab appears to be beneficial in relation to disease severity and prognosis in patients with fludarabine-refractory B-cell chronic lymphocytic leukemia.
传统上，B细胞慢性淋巴细胞白血病采用烷化剂和嘌呤类似物进行治疗。阿仑单抗是一种CD52单克隆抗体，在化疗难治性B细胞慢性淋巴细胞白血病中具有显著的临床活性，它的引入伴随着与化疗不同的副作用谱。静脉注射阿仑单抗通常会伴随短暂的输液相关副作用，主要表现为流感样症状。使用皮质类固醇预防可减少这些反应，并且在持续治疗期间会逐渐消退。另外，皮下注射阿仑单抗可能会显著减少全身副作用的发生，但在大多数患者中会导致有限的短暂局部皮肤反应。约20%的患者可能会出现4级中性粒细胞减少，但通常是短暂的和/或对集落刺激因子治疗反应迅速；发热性中性粒细胞减少发作并不常见。阿仑单抗的主要副作用是T细胞耗竭，导致感染风险增加，尤其是巨细胞病毒再激活。这一事件通常发生在治疗开始后3至8周，与T细胞最低点一致。通过警惕和早期检测，这些感染通常是可控的，不会导致器官衰竭。初步数据表明，阿仑单抗治疗后的其他感染发生率似乎并不高于预期，这可能是由于普遍预防性使用复方新诺明（甲氧苄啶和磺胺甲恶唑）和伐昔洛韦以及临床肿瘤消退的缘故。对于氟达拉滨难治性B细胞慢性淋巴细胞白血病患者，阿仑单抗总的安全性概况在疾病严重程度和预后方面似乎是有益的。
