Montillo Marco, Tedeschi Alessandra, Miqueleiz Sara, Veronese Silvio, Cairoli Roberto, Intropido Liliana, Ricci Francesca, Colosimo Anna, Scarpati Barbara, Montagna Michela, Nichelatti Michele, Regazzi Mario, Morra Enrica
Department of Hematology, Laboratory of Flow Cytometry, Transfusion Medicine Service, Niguarda Ca'Granda Hospital, Milano, Milan, Italy.
J Clin Oncol. 2006 May 20;24(15):2337-42. doi: 10.1200/JCO.2005.04.6037. Epub 2006 Apr 17.
Treatment with alemtuzumab has resulted in negative responses for minimal residual disease (MRD) in patients with chronic lymphocytic leukemia (CLL). In a prior analysis we demonstrated that it is possible to achieved MRD negativity, as assessed by polyclonality of immunoglobulin heavy chain after consolidation with alemtuzumab. This phase II study evaluated 34 patients with CLL who received alemtuzumab consolidation in an effort to improve the quality of their response to fludarabine-based induction. Subsequent peripheral blood stem-cell (PBSC) collection and transplantation, tolerability, and pharmacokinetics also were assessed.
Thirty-four patients younger than 65 years who had a clinical response to fludarabine-based induction therapy received alemtuzumab 10 mg subcutaneously three times per week for 6 weeks. PBSCs were collected after mobilization with cytarabine and granulocyte colony-stimulating factor. Blood samples for pharmacokinetics study were taken between days 1 and 31.
The complete response rate improved from 35% after fludarabine induction to 79.4% after alemtuzumab consolidation, including 19 patients (56%) who achieved MRD negativity. The most common adverse events were injection-site reactions and fever. Cytomegalovirus reactivation occurred in 18 patients, all of whom were successfully treated with oral ganciclovir. PBSC collection was successful in 24 (92%) of 26 patients, and 18 patients underwent autologous PBSC transplantation. Alemtuzumab plasma concentrations increased gradually during the first 2 weeks and accumulated more rapidly thereafter.
Subcutaneously administered alemtuzumab was effective, safe, and well tolerated as consolidation therapy in patients with CLL who responded to fludarabine induction therapy. Subsequent PBSCT was feasible thereafter.
用阿仑单抗治疗对慢性淋巴细胞白血病（CLL）患者的微小残留病（MRD）产生了阴性反应。在之前的一项分析中，我们证明通过阿仑单抗巩固治疗后免疫球蛋白重链的多克隆性评估，有可能实现MRD阴性。这项II期研究评估了34例接受阿仑单抗巩固治疗的CLL患者，以努力提高他们对基于氟达拉滨诱导治疗的反应质量。随后还评估了外周血干细胞（PBSC）采集和移植、耐受性及药代动力学。
34例年龄小于65岁且对基于氟达拉滨诱导治疗有临床反应的患者，接受皮下注射阿仑单抗10 mg，每周3次，共6周。在用阿糖胞苷和粒细胞集落刺激因子动员后采集PBSC。在第1天至第31天之间采集用于药代动力学研究的血样。
完全缓解率从氟达拉滨诱导后的35%提高到阿仑单抗巩固后的79.4%，包括19例（56%）实现MRD阴性的患者。最常见的不良事件是注射部位反应和发热。18例患者发生巨细胞病毒再激活，所有患者均成功接受口服更昔洛韦治疗。26例患者中有24例（92%）PBSC采集成功，18例患者接受了自体PBSC移植。阿仑单抗血浆浓度在最初2周逐渐升高，此后积累更快。
皮下注射阿仑单抗作为巩固治疗对氟达拉滨诱导治疗有反应的CLL患者有效、安全且耐受性良好。随后进行PBSCT是可行的。
