Bernengo Maria Grazia, Quaglino Pietro, Comessatti Alessandra, Ortoncelli Michela, Novelli Mauro, Lisa Francesco, Fierro Maria Teresa
Department of Biomedical Sciences and Human Oncology, Section of Dermatology, 1st Dermatologic Division, University of Turin, Turin, Italy.
Haematologica. 2007 Jun;92(6):784-94. doi: 10.3324/haematol.11127.
Alemtuzumab may be effective in Sézary syndrome (SS), an aggressive cutaneous T-cell lymphoma, but is associated with severe hematologic toxicity and infections. This study investigated whether low-dose subcutaneous alemtuzumab can induce hematologic, immunologic, and clinical responses similar to those obtained with the standard regimen, but with less toxicity.
Fourteen SS patients were enrolled: 11 had relapsed/refractory disease and three had untreated SS with high counts of circulating Sézary cells (SC). Four received 3 mg alemtuzumab on day 1, 10 mg on day 3, then 15 mg on alternating days; circulating SC were evaluated after the fourth 15 mg dose and treatment was interrupted in the presence of counts <1,000/mm (3). A reduced dosage (3 mg on day 1, then 10 mg on alternating days) was administered to the remaining patients, with SC counted before every injection, until a reduction to values of <1,000/mm (3).
The median SC count decreased by 95.5%. Overall, 12/14 patients (85.7%) achieved a clinical response, with three complete responses (21.4%). After a median follow-up of 16 months, the median time-to-treatment failure is 12 months. Infectious complications occurred in 28.6% of patients, all included in the group treated with 15 mg. No patient in the group treated with 10 mg developed hematologic toxicity or infections. An early recovery of circulating NK, B and CD3+CD8+ cells occurred after the first cycle.
Subcutaneous alemtuzumab at very low doses (10 mg maximum per administration), given for a short period based on SC levels, has a good toxicity profile, high response rate and causes durable remissions in SS patients with high tumor burden in the peripheral blood.
阿仑单抗可能对蕈样肉芽肿综合征（SS）有效，这是一种侵袭性皮肤T细胞淋巴瘤，但与严重的血液学毒性和感染相关。本研究调查了低剂量皮下注射阿仑单抗是否能诱导出与标准方案相似的血液学、免疫学和临床反应，但毒性更小。
纳入14例SS患者：11例为复发/难治性疾病，3例为未经治疗的SS且循环中蕈样肉芽肿细胞（SC）计数高。4例患者在第1天接受3mg阿仑单抗，第3天接受10mg，然后隔日接受15mg；在第四次15mg剂量后评估循环SC，当计数<1000/mm³时中断治疗。其余患者给予减量方案（第1天3mg，然后隔日10mg），每次注射前计数SC，直至降至<1000/mm³。
SC计数中位数下降了95.5%。总体而言，12/14例患者（85.7%）获得临床缓解，3例完全缓解（21.4%）。中位随访16个月后，治疗失败的中位时间为12个月。28.6%的患者发生感染并发症，均在接受15mg治疗的组中。接受10mg治疗的组中无患者发生血液学毒性或感染。第一个周期后循环NK、B和CD3+CD8+细胞早期恢复。
基于SC水平短期给予极低剂量（每次最大10mg）皮下注射阿仑单抗，毒性谱良好，缓解率高，可使外周血肿瘤负荷高的SS患者获得持久缓解。
