Phase 2 study of the efficacy and safety of the combination of arsenic trioxide, interferon alpha, and zidovudine in newly diagnosed chronic adult T-cell leukemia/lymphoma (ATL)
Phase 2 study of the efficacy and safety of the combination of arsenic trioxide, interferon alpha, and zidovudine in newly diagnosed chronic adult T-cell leukemia/lymphoma (ATL)
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DOI：
10.1182/blood-2009-03-211821
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发表时间：
2009-06-25
期刊：
影响因子：
20.3
通讯作者：
Bazarbachi, Ali
中科院分区：
文献类型：
--
作者：
Kchour, Ghada;Tarhini, Mahdi;Bazarbachi, Ali
成人T细胞白血病/淋巴瘤(ATL)对化疗耐药，预后不佳，尤其是急性和淋巴瘤亚型。齐多夫定和干扰素-α联合应用取得了令人振奋的结果。慢性ATL的预后相对较好，但当患者采用警惕等待政策或化疗时，长期存活率较低。在ATL细胞系中，三氧化二砷通过蛋白酶体降解TAX来阻断组成性的核因子-kappaB的激活，并增强干扰素-α的凋亡效应。临床上，砷/干扰素治疗对难治性侵袭性ATL患者有一定疗效。这些结果促使我们研究了砷、干扰素-α和齐多夫定在10名新诊断的慢性ATL患者中的有效性和安全性。观察到令人印象深刻的100%有效率，其中完全缓解7例，完全缓解2例，但循环异型淋巴细胞超过5%，部分缓解1例。反应迅速，未见复发。副作用是中度的，主要是血液学的。总之，用砷、干扰素-α和齐多夫定治疗慢性ATL是可行的，并且表现出令人印象深刻的有效率和中等毒性。长期的随访将澄清这是否会转化为疾病的治愈。总体而言，这些临床结果加强了癌基因靶向癌症治疗的概念。(血。2009；113：6528-6532)
Adult T-cell leukemia/lymphoma (ATL) is resistant to chemotherapy and carries a dismal prognosis particularly for the acute and lymphoma subtypes. Promising results were obtained with the combination of zidovudine and interferon-alpha. Chronic ATL has a relatively better outcome, but poor long-term survival is noted when patients are managed with a watchful-waiting policy or with chemotherapy. In ATL cell lines, arsenic trioxide shuts off constitutive NF-kappa B activation and potentiates interferon-alpha apoptotic effects through proteasomal degradation of Tax. Clinically, arsenic/interferon therapy exhibits some efficacy in refractory aggressive ATL patients. These results prompted us to investigate the efficacy and safety of the combination of arsenic, interferon-alpha, and zidovudine in 10 newly diagnosed chronic ATL patients. An impressive 100% response rate was observed including 7 complete remissions, 2 complete remissions but with more than 5% circulating atypical lymphocytes, and 1 partial response. Responses were rapid and no relapse was noted. Side effects were moderate and mostly hematologic. In conclusion, treatment of chronic ATL with arsenic, interferon-alpha, and zidovudine is feasible and exhibits an impressive response rate with moderate toxicity. Long-term follow up will clarify whether this will translate to disease cure. Overall, these clinical results strengthen the concept of oncogene-targeted cancer therapy. (Blood. 2009; 113: 6528-6532)