Anti-B4 blocked ricin post chemotherapy in patients with chronic lymphocytic leukemia - Long-term follow-up of a monoclonal antibody-based approach to residual disease
Anti-B4 blocked ricin post chemotherapy in patients with chronic lymphocytic leukemia - Long-term follow-up of a monoclonal antibody-based approach to residual disease
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DOI：
10.1080/1042819031000116706
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发表时间：
2003-09-01
影响因子：
2.6
通讯作者：
O'Brien, SM
中科院分区：
文献类型：
--
作者：
Tsimberidou, AM;Giles, FJ;O'Brien, SM
抗b4阻断蓖麻毒素是一种由抗b4小鼠单克隆抗体和“阻断蓖麻毒素”组成的免疫毒素。抗b4单克隆抗体直接针对CD19抗原，CD19抗原在b淋巴细胞上表达。对b细胞慢性淋巴细胞白血病（CLL）化疗后残留病变患者进行了抗b4阻断蓖麻毒素的II期研究。11例患者每日按30马克杯/千克瘦体重（LBM）连续输注抗b4阻断蓖麻毒素，连续输注7天，每隔14天重复输注一次。没有患者达到客观反应。治疗无效的主要原因是存在腺病和残留骨髓疾病。3例患者骨髓和外周血均出现免疫表型反应。在抗b4阻断蓖麻毒素后，6例重排IgH和/或Igkappa患者中有3例为种系细胞。存活患者的中位随访时间为8.6年。中位生存期为5.8年（范围0-8.8年）。所有病人都有进展。中位进展时间为0.8年（范围0.3-3.0）。输注相关毒性均为1-2级。最常见的毒性是转氨炎。2例患者出现人抗小鼠抗体（HAMA）和/或人抗蓖麻毒素抗体（HARA）。抗b4阻断蓖麻毒素耐受性良好，但在化疗后残余CLL患者中活性有限。
Anti-B4-blocked ricin is an immunotoxin consisting of anti-B4 murine monoclonal antibody and "blocked ricin" toxin. The anti-B4 monoclonal antibody is directed against the CD19 antigen, which is expressed on B-lymphocytes. A phase II study of anti-B4 blocked ricin toxin in patients with B-cell chronic lymphocytic leukemia (CLL) with residual disease after chemotherapy was conducted. Eleven patients received anti-B4 blocked ricin at 30 mug/kg lean body mass (LBM) daily by continuous infusion for 7 days followed with repeat infusion administered at 14-day intervals. No patient achieved an objective response. The major reasons for failure to respond were the presence of adenopathy and residual marrow disease. Three patients achieved immunophenotypic response in marrow and peripheral blood. Three of 6 patients with rearranged IgH and/or Igkappa were germline after anti-B4 blocked ricin. The median follow-up of surviving patients is 8.6 years. The median survival is 5.8 years (range, 0.0-8.8). All patients have progressed. The median time to progression was 0.8 years (range, 0.3-3.0). Infusion-related toxicities were all grade 1-2. The most common toxicity was transaminitis. Human antimouse antibody (HAMA) and/or human antiricin antibody (HARA) development was documented in 2 patients. Anti-B4 blocked ricin was well tolerated but had limited activity in patients with residual CLL after chemotherapy.