Chemoimmunotherapy reinduction with epratuzumab in children with acute lymphoblastic leukemia in marrow relapse: A children's oncology group pilot study
Chemoimmunotherapy reinduction with epratuzumab in children with acute lymphoblastic leukemia in marrow relapse: A children's oncology group pilot study
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DOI：
10.1200/jco.2007.15.3528
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发表时间：
2008-08-01
影响因子：
45.3
通讯作者：
Adamson, Peter C.
中科院分区：
文献类型：
--
作者：
Raetz, Elizabeth A.;Cairo, Mitchell S.;Adamson, Peter C.
目的观察依帕珠单抗（epratuzumab）单药及联合诱导化疗治疗儿童复发性急性淋巴细胞白血病（ALL）的耐受性和血药浓度，初步评价肿瘤靶向性和疗效。（依帕珠单抗360 mg/m2/剂，静脉注射，每周2次，共4次），随后依帕珠单抗联合标准再诱导化疗，每周4次。在6周结束时测定形态学和微小残留病（MRD）反应。依帕珠单抗的血清浓度测定前和30分钟后输注，和CD 22靶向效率测定后依帕珠单抗administration.Results的CD 22表达的定量变化15例（12完全评估毒性）与第一个或以后的CD 22阳性ALL骨髓复发招募本研究的可行性部分，从2005年12月至2006年6月。发生了两种剂量限制性毒性：一种病因不明的4级癫痫发作和一种无症状的3级ALT升高。除1例患者外，所有患者在给药后24小时内均未通过流式细胞术在外周血白血病原始细胞上检测到表面CD 22，表明依帕珠单抗可有效靶向白血病细胞。结论依帕珠单抗联合标准再诱导化疗治疗复发性CD 22阳性ALL患儿是可行的，且耐受性良好。CD 22靶向治疗是有效的，大多数患者获得了良好的早期反应。
Purpose To determine the tolerability and serum concentration of epratuzumab, a humanized monoclonal antibody targeting CD22, administered alone and in combination with reinduction chemotherapy in children with relapsed acute lymphoblastic leukemia (ALL), and to preliminarily assess tumor targeting and efficacy.Patients and Methods Therapy consisted of a single-agent phase (epratuzumab 360 mg/m(2)/dose intravenously twice weekly x four doses), followed by four weekly doses of epratuzumab in combination with standard reinduction chemotherapy. Morphologic and minimal residual disease (MRD) responses were determined at the end of this 6-week period. Serum concentrations of epratuzumab were determined before and 30 minutes after infusions, and CD22 targeting efficiency was determined by quantifying changes in CD22 expression after epratuzumab administration.Results Fifteen patients (12 fully assessable for toxicity) with first or later CD22-positive ALL marrow relapse enrolled on the feasibility portion of this study from December 2005 to June 2006. Two dose-limiting toxicities occurred: one grade 4 seizure of unclear etiology and one asymptomatic grade 3 ALT elevation. In all but one patient, surface CD22 was not detected by flow cytometry on peripheral blood leukemic blasts within 24 hours of drug administration, indicating effective targeting of leukemic cells by epratuzumab. Nine patients achieved a complete remission after chemoimmunotherapy, seven of whom were MRD negative.Conclusion Treatment with epratuzumab plus standard reinduction chemotherapy is feasible and acceptably tolerated in children with relapsed CD22-positive ALL. CD22 targeting was efficient, and the majority of patients achieved favorable early responses.