Efficacy of the anti-CD22 recombinant immunotoxin BL22 in chemotherapy-resistant hairy-cell leukemia
Efficacy of the anti-CD22 recombinant immunotoxin BL22 in chemotherapy-resistant hairy-cell leukemia
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DOI：
10.1056/nejm200107263450402
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发表时间：
2001-07-26
影响因子：
158.5
通讯作者：
Pastan, I
中科院分区：
文献类型：
--
作者：
Kreitman, RJ;Wilson, WH;Pastan, I
毛细胞白血病对嘌呤类似物（包括氯德里滨）治疗有耐药性，预后较差。我们测试了一种针对白血病毛细胞强烈表达的表面抗原的免疫毒素的安全性和有效性。方法将含有抗cd22可变结构域（Fv）与假单胞菌外毒素融合的重组免疫毒素RFB4(dsFv)-PE38 （BL22）进行剂量递增试验，每隔一天静脉滴注3次。结果16例耐药患者中，11例完全缓解，2例部分缓解。没有反应的三名患者接受了低剂量的BL22或先前存在的毒素中和抗体。在11例完全缓解的患者中，2例在骨髓或血液中有极小的残留疾病。在中位随访16个月（范围10 - 23个月）期间，11例完全缓解的患者中有3例复发并得到了治疗；所有这些患者都有第二次完全缓解。16例患者中有2例在用BL22治疗的第二个周期中出现了严重但完全可逆的溶血性尿毒症综合征。常见的毒性作用包括短暂性低白蛋白血症和转氨酶水平升高。结论BL22可诱导对嘌呤类似物耐药的毛细胞白血病患者完全缓解。[J] .中华医学杂志，2001;31(2):391 - 391。版权所有(C) 2001马萨诸塞州医学协会。
Background Hairy-cell leukemia that is resistant to treatment with purine analogues, including cladribine, has a poor prognosis. We tested the safety and efficacy of an immunotoxin directed against a surface antigen that is strongly expressed by leukemic hairy cells.Methods RFB4(dsFv)-PE38 (BL22), a recombinant immunotoxin containing an anti-CD22 variable domain (Fv) fused to truncated pseudomonas exotoxin, was administered in a dose-escalation trial by intravenous infusion every other day for a total of three doses.Results Of 16 patients who were resistant to cladribine, 11 had a complete remission and 2 had a partial remission with BL22. The three patients who did not have a response received low doses of BL22 or had preexisting toxin-neutralizing antibodies. Of the 11 patients in complete remission, 2 had minimal residual disease in the bone marrow or blood. During a median follow-up of 16 months ( range, 10 to 23), 3 of the 11 patients who had a complete response relapsed and were retreated; all of these patients had a second complete remission. In 2 of the 16 patients, a serious but completely reversible hemolytic uremic syndrome developed during the second cycle of treatment with BL22. Common toxic effects included transient hypoalbuminemia and elevated aminotransferase levels.Conclusions BL22 can induce complete remissions in patients with hairy-cell leukemia that is resistant to treatment with purine analogues. (N Engl J Med 2001; 345: 241-7.) Copyright (C) 2001 Massachusetts Medical Society.