Molecular remission induction with retinoic acid and anti-CD33 monoclonal antibody HuM195 in acute promyelocytic leukemia.
Molecular remission induction with retinoic acid and anti-CD33 monoclonal antibody HuM195 in acute promyelocytic leukemia.
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发表时间：
2000-02
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通讯作者：
J. Jurcic;T. Deblasio;Larry J. Dumont;T. Yao;D. Scheinberg
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作者：
J. Jurcic;T. Deblasio;Larry J. Dumont;T. Yao;D. Scheinberg
尽管用维甲酸（RA）达到完全缓解，但大多数急性早幼粒细胞白血病（APL）患者具有可通过逆转录-PCR（RT-PCR）扩增检测到的微小残留病变。HuM195是一种与细胞表面抗原CD33反应的人源化单克隆抗体，特异性靶向并杀死髓性白血病细胞。我们用RT-PCR方法研究了HuM195是否能消除APL患者的微小残留病。在用RA和/或化疗达到临床完全缓解后，患者每周两次接受HuM195，持续3周。首次缓解的患者接受巩固化疗，通常使用3个周期的伊达洛酮和阿糖胞苷。第二次或更长时间缓解的患者未接受化疗。所有患者均接受为期六个月的两剂HuM195维持治疗。27例首次缓解的患者中有25例在HuM195治疗前具有阳性RT-PCR测定。在22例可评价阳性RT-PCR检测转化的患者中，11例（50%）在HuM195治疗后变为RT-PCR阴性，无需额外治疗。在仅接受RA作为诱导的患者亚组中，18例可评估患者中有8例（44%）在HuM195治疗后但化疗前的RT-PCR测定结果为阴性。在早期研究中治疗的类似患者中，34例RA诱导缓解并维持药物治疗1个月的患者中有7例（21%）在化疗前为RT-PCR阴性（P = 0.07）。27例新诊断的APL患者中有25例（93%）保持临床完全缓解7+至58+个月，中位随访时间为29个月。7例第二或第三次缓解患者和1例分子复发患者也接受了治疗。这些患者中只有1例在用HuM195治疗后变为RT-PCR阴性。这些数据表明，HuM195对APL中的微小残留病具有活性，特别是在新诊断的患者中。
Despite achieving complete remission with retinoic acid (RA), most patients with acute promyelocytic leukemia (APL) have minimal residual disease detectable by reverse transcription-PCR (RT-PCR) amplification. HuM195, a humanized monoclonal antibody reactive with the cell surface antigen CD33, specifically targets and kills myeloid leukemia cells. We studied whether HuM195 could eliminate minimal residual disease in patients with APL by using RT-PCR. After attaining clinical complete remission with RA and/or chemotherapy, patients received HuM195 twice weekly for 3 weeks. Patients in first remission were given consolidation chemotherapy, generally with three cycles of idarubicin and cytarabine. Patients in second or greater remission did not receive chemotherapy. All patients received six monthly courses of maintenance with two doses of HuM195. Twenty-five of 27 patients treated in first remission had positive RT-PCR determinations before HuM195 treatment. Of the 22 patients evaluable for conversion of positive RT-PCR assays, 11 (50%) became RT-PCR negative after HuM195 treatment without additional therapy. Within the subset of patients who received RA alone as induction, 8 of 18 evaluable patients (44%) had negative RT-PCR determinations after HuM195 treatment but before chemotherapy. Among similar patients treated on earlier studies, 7 of 34 patients (21%) induced into remission with RA and then maintained on the drug for 1 month were RT-PCR negative before chemotherapy (P = 0.07). Twenty-five of 27 patients with newly diagnosed APL (93%) remain in clinical complete remission for 7+ to 58+ months, with median follow-up of 29 months. Seven patients in second or third remission and one patient in molecular relapse were also treated. Only one of these patients became RT-PCR negative after treatment with HuM195. These data suggest that HuM195 has activity against minimal residual disease in APL, particularly in newly diagnosed patients.