Tetra-arsenic tetra-sulfide for the treatment of acute promyelocytic leukemia: a pilot report
Tetra-arsenic tetra-sulfide for the treatment of acute promyelocytic leukemia: a pilot report
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DOI：
10.1182/blood.v99.9.3136
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发表时间：
2002-05-01
期刊：
影响因子：
20.3
通讯作者：
Chen, SS
中科院分区：
文献类型：
--
作者：
Lu, DP;Qiu, JY;Chen, SS
在过去的6年中，我们用一种新的砷制剂--口服四硫化四砷(As4S4)治疗了129例急性早幼粒细胞白血病(APL)。19例初诊APL，7例首次复发，103例血液学完全缓解(HCR)。所有新诊断的APL患者和所有血液病复发患者均实现了HCR。在新诊断的16例患者中，14例获得了细胞遗传学和分子生物学完全缓解(CR)。7例血液病复发患者中有5例获得细胞遗传学和分子学完全缓解。在HCR组，基线时PML-RARpha阳性的44例患者中有35例转为阴性。新诊断组1年和3年无瘤生存率分别为86.1%和76.6%，中位随访时间13.5个月(2~40个月)。HCR组1年DFS率为96.7%，6年DFS率为87.4%，中位随访期为23个月(2~71个月)。As4S4治疗耐受性良好，仅有中度副作用，包括校正的QT间期无症状延长、肝酶水平一过性升高、皮疹和轻微的胃肠道不适；既没有发生骨髓抑制，也没有明显的长期副作用。As4S4治疗过程中可见APL早幼粒细胞变性或凋亡。药代动力学研究表明，该制剂吸收迅速。大多数尿砷排出发生在最初的24小时内。停用As4S4后，血和尿砷水平均下降。我们的结果首次表明，在APL患者的缓解诱导和维持治疗中，单独使用As4S4治疗是高效和安全的，无论疾病分期如何。(C)2002年，由美国血液病学会公布。
In the past 6 years, we treated 129 patients who had acute promyelocytic leukemia (APL) with a new arsenic agent, oral tetra-arsenic tetra-sulfide (As4S4). Nineteen of the patients had newly diagnosed APL, 7 had first relapse, and 103 had hematologic complete remission (HCR). HCR was achieved In all patients with newly diagnosed APL and in all those with hematologic relapse. Of 16 patients with newly diagnosed disease and available cytogenetic and molecular analyses, 14 had cytogenetic and molecular complete remission (CR). Cytogenetic and molecular CR was also obtained In 5 of the 7 patients with hematologic relapse. In the HCR group, 35 of 44 patients positive for PML-RARalpha at baseline became negative. In the newly diagnosed group, estimated disease-free survival (DFS) rates for 1 and 3 years were 86.1% and 76.6%, respectively, with a median follow-up time of 13.5 months (range, 2-40 months). In the HCR group, DFS rates for 1 and 6 years were 96.7% and 87.4%, respectively, with a median follow-up of 23 months (range, 2-71 months). Treatment with As4S4 Was well tolerated, with only moderate side effects, including asymptomatic prolongation of corrected QT Interval, transient elevation In liver enzyme levels, rash, and mild gastrointestinal discomfort; neither myelosuppression nor appreciable long-term side effects occurred. Degeneration or apoptosis of APL promyelocytes was observed during As4S4 therapy. Pharmacokinetic studies showed that the agent was absorbed rapidly. Most urinary arsenic excretion occurred within the first 24 hours. Both blood and urinary arsenic levels declined after discontinuation of As4S4. Our results show, for the first time, that As4S4 treatment alone is highly effective and safe in both remission induction and maintenance therapy In patients with APL, regardless of disease stage. (C) 2002 by The American Society of Hematology.