Pangalis G A, Dimopoulou M N, Angelopoulou M K, Tsekouras C, Vassilakopoulos T P, Vaiopoulos G, Siakantaris M P
1st Department of Internal Medicine, National and Kapodistrian University of Athens, Laikon General Hospital, Greece.
Med Oncol. 2001;18(2):99-107. doi: 10.1385/mo:18:2:99.
Campath-1H is a humanized monoclonal antibody targeted against the CDw52 membrane antigen of lymphocytes, which causes complement and antibody-dependent cell-mediated cytotoxicity. Campath-1H has been used in B-chronic lymphocytic leukemia (B-CLL), T-prolymphocytic leukemia (T-PLL), and low-grade non-Hodgkin's lymphoma (LGNHL). Campath-1H is administered intravenously thrice weekly for up to 12 wk, at an initial dose of 3 mg, escalated to 10 and 30 mg. The responses (complete [CR] and partial [PR]) obtained in untreated B-CLL patients are of the order of 90%. In previously treated B-CLL patients, responses are of the order of approximately 40%, with 2-4% CRs. Responses are more prominent in the blood and bone marrow compared to the lymph nodes. The median duration of response is 9-12 mo. Because of the antibody's higher activity on circulating lymphocytes, it has been used for in vivo purging of residual disease in B-CLL, followed by autologous stem-cell transplantation. In heavily pretreated advanced stage LGNHL, response is achieved only in 14% of cases with B-phenotype; a 50% response rate is noted in mycosis fungoides. In T-PLL, the CR rate is approximately 60%. Promising results have been reported in a small number of patients with refractory autoimmune thrombocytopenia of lymphoproliferative disorders. The main complications of Campath-1H treatment are caused by tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 release, usually during the first intravenous infusion, and include fever, rigor, nausea, vomiting, and hypotension responsive to steroids. These side effects are usually less severe with subsequent infusions and can be prevented by paracetamol and antihistamines. Immunosupression resulting from normal B- and T-lymphocyte depletion is frequent, resulting in an increased risk for opportunistic infections. More clinical trials in a larger number of patients are necessary to determine the exact role and indications of Campath-1H in lymphoproliferative disorders.
Campath-1H是一种人源化单克隆抗体，靶向淋巴细胞的CDw52膜抗原，可引起补体和抗体依赖性细胞介导的细胞毒性。Campath-1H已用于B细胞慢性淋巴细胞白血病（B-CLL）、T原淋巴细胞白血病（T-PLL）和低度非霍奇金淋巴瘤（LGNHL）。Campath-1H每周静脉注射三次，共12周，初始剂量为3mg，逐步增至10mg和30mg。未经治疗的B-CLL患者的缓解率（完全缓解[CR]和部分缓解[PR]）约为90%。在先前接受过治疗的B-CLL患者中，缓解率约为40%，完全缓解率为2%-4%。与淋巴结相比，血液和骨髓中的缓解更为显著。缓解的中位持续时间为9-12个月。由于该抗体对循环淋巴细胞具有更高的活性，它已被用于B-CLL残留疾病的体内清除，随后进行自体干细胞移植。在经过大量预处理的晚期LGNHL中，只有14%的B表型病例有反应；蕈样肉芽肿的反应率为50%。在T-PLL中，完全缓解率约为60%。在少数难治性自身免疫性血小板减少性淋巴增殖性疾病患者中也报告了有希望的结果。Campath-1H治疗的主要并发症是由肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6释放引起的，通常在首次静脉输注期间，包括发热、寒战、恶心、呕吐和对类固醇有反应的低血压。这些副作用在随后的输注中通常不太严重，可通过对乙酰氨基酚和抗组胺药预防。正常B淋巴细胞和T淋巴细胞耗竭导致的免疫抑制很常见，导致机会性感染风险增加。需要在更多患者中进行更多临床试验，以确定Campath-1H在淋巴增殖性疾病中的确切作用和适应证。
