Phase II trial of arsenic trioxide and alpha interferon in patients with relapsed/refractory adult T-cell leukemia/lymphoma
Phase II trial of arsenic trioxide and alpha interferon in patients with relapsed/refractory adult T-cell leukemia/lymphoma
复制标题
DOI：
10.1038/sj.thj.6200374
复制
发表时间：
2004-01-01
期刊：
影响因子：
--
通讯作者：
Bazarbachi, A
中科院分区：
文献类型：
--
作者：
Hermine, O;Dombret, H;Bazarbachi, A
人类嗜T淋巴细胞病毒I型相关的成人T细胞白血病/淋巴瘤由于其对化疗的内在抗性而预后非常差。虽然齐多夫定（AZT）和α-干扰素（IFN）产生一些反应，并改善ATL预后，替代疗法是必要的。三氧化二砷与干扰素协同诱导ATL白血病细胞生长停滞和凋亡。这些结果促使我们启动了11期临床试验的作为/干扰素组合在7例复发/难治性ATL（4例急性和3例淋巴瘤）。4例患者表现出明确的初始缓解（1例完全缓解和3例部分缓解）。然而，由于毒性（3名患者）或随后的进展（4名患者），在中位数22天后停止治疗。6名患者最终死于疾病进展（5名患者）或感染（1名患者），但其余患者仍然存活，32个月时无疾病。药代动力学研究表明，砷的最大血液浓度（中位数0.46 μ M）是缓慢达到（8-15天）。总之，砷/干扰素治疗是可行的，并表现出抗白血病的效果，预后非常差的ATL患者，尽管有显着的毒性。未来的研究应评估砷治疗的最佳时机：一线使用IFN/AZT或诱导后作为维持治疗。
Human T-cell lymphotropic virus type I associated adult T-cell leukemia/lymphoma carries a very poor prognosis due to its intrinsic resistance to chemotherapy. Although zidovudine (AZT) and alpha-interferon (IFN) yield some responses and improve ATL prognosis, alternative therapies are needed. Arsenic trioxide (As) dramatically synergizes with IFN to induce growth arrest and apoptosis of ATL leukemia cells in vitro. These results prompted us to initiate a phase 11 trial of As/IFN combination in seven patients with relapsed/refractory ATL (four acute and three lymphoma). Four patients exhibited a clear initial response (one complete remission and three partial remissions). Yet, the treatment was discontinued after a median of 22 days because of toxicity (three patients) Or Subsequent progression (four patients). Six patients eventually died from progressive disease (five patients) or infection (one patient), but the remaining patient is still alive and disease free at 32 months. Pharmacokinetic studies showed that maximum arsenic blood levels (median 0.46 muM) were slowly achieved (8-15 days). In conclusion, arsenic/IFN treatment is feasible and exhibits an anti-leukemia effect in very poor prognosis ATL patients despite a significant toxicity. Future Studies should assess the best timing for arsenic therapy: frontline with IFN/AZT or as maintenance after induction.