Responses in refractory hairy cell leukemia to a recombinant immunotoxin
Responses in refractory hairy cell leukemia to a recombinant immunotoxin
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DOI：
10.1182/blood.v94.10.3340.422k19_3340_3348
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发表时间：
1999-11-15
期刊：
影响因子：
20.3
通讯作者：
Pastan, I
中科院分区：
文献类型：
--
作者：
Kreitman, RJ;Wilson, WH;Pastan, I
我们报告了4例毛细胞白血病（HCL）患者中4例的主要反应，这些患者最近接受了重组免疫毒素LMB-2的I期试验，该免疫毒素旨在靶向CD25（+）恶性肿瘤，由抗tac（抗CD25）抗体的Fv部分组成，与假单胞菌外毒素a的38-kD截断形式融合，以前被称为抗tac (Fv)-PE38，所有4例HCL患者对HCL的标准和补偿性治疗都有耐药性。包括2-氯脱氧腺苷（CdA）和干扰素α，所有患者在单周期治疗后均对LMB-2有反应，1例患者治疗2个周期后完全缓解（CR），血液和骨髓中HCL细胞消退，脾肿大和全血细胞减少。与典型的CdA治疗后的CR患者一样，骨髓抽吸的流式细胞术可以检测到微小的残留疾病。该患者11个月后未复发。另外三名患者的恶性循环细胞减少了98%至99.8%。这些结果证明了重组含fv蛋白的靶向治疗在临床上是有用的。LMB-2可能是化疗耐药CD25+ HCL患者的一种有效的新疗法，这是美国政府的一项研究。它的使用没有限制。
We report major responses in 4 of 4 patients with hairy cell leukemia (HCL) who have recently been treated on a phase I trial with the recombinant immunotoxin LMB-2, The immunotoxin, designed to target CD25(+) malignancies, is composed of the Fv portion of the anti-Tac (anti-CD25) antibody, fused to a 38-kD truncated form of Pseudomonas exotoxin A, and has previously been called anti-Tac(Fv)-PE38, All 4 HCL patients were resistant to standard and salvage therapies for HCL, including 2-chlorodeoxyadenosine (CdA) and interferon alpha, and all patients responded to LMB-2 after a single cycle, One patient treated with 2 cycles had a complete remission (CR), with regression of HCL cells from the blood and marrow and resolution of splenomegaly and pancytopenia. As is typical for patients in CR after treatment with CdA, minimal residual disease was detectable by flow cytometry of the bone marrow aspirate. This patient has not relapsed after 11 months. Three other patients had 98% to 99.8% reductions in malignant circulating cells. These results represent a proof of principal that targeted therapy with recombinant Fv-containing proteins can be clinically useful. LMB-2 may be an effective new therapy for patients with chemotherapy-resistant CD25+ HCL, This is a US government work. There are no restrictions on its use.