Hermine Olivier, Dombret Hervé, Poupon Joel, Arnulf Bertrand, Lefrère Francois, Rousselot Phillippe, Damaj Gandhi, Delarue Richard, Fermand Jean Paul, Brouet Jean Claude, Degos Laurent, Varet Bruno, de Thé Hugues, Bazarbachi Ali
Department of Hematology, Necker Hospital, Paris, France.
Hematol J. 2004;5(2):130-4. doi: 10.1038/sj.thj.6200374.
Human T-cell lymphotropic virus type 1 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 II 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 microM) 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.
1型人类嗜T细胞病毒相关的成人T细胞白血病/淋巴瘤因其对化疗的固有抗性而预后极差。虽然齐多夫定（AZT）和α干扰素（IFN）能产生一些反应并改善成人T细胞白血病/淋巴瘤的预后，但仍需要其他治疗方法。三氧化二砷（As）与IFN显著协同作用，在体外诱导成人T细胞白血病/淋巴瘤细胞生长停滞和凋亡。这些结果促使我们对7例复发/难治性成人T细胞白血病/淋巴瘤患者（4例急性型和3例淋巴瘤型）开展三氧化二砷/IFN联合治疗的II期试验。4例患者出现明显的初始反应（1例完全缓解，3例部分缓解）。然而，由于毒性（3例患者）或随后的病情进展（4例患者），治疗在中位22天后中断。6例患者最终死于疾病进展（5例患者）或感染（1例患者），但其余1例患者在32个月时仍存活且无疾病。药代动力学研究表明，砷的最高血药浓度（中位值0.46微摩尔/升）达到缓慢（8 - 15天）。总之，尽管有显著毒性，但砷/IFN治疗在预后极差的成人T细胞白血病/淋巴瘤患者中是可行的，并显示出抗白血病作用。未来的研究应评估砷治疗的最佳时机：与IFN/AZT联合用于一线治疗或诱导后作为维持治疗。
