Klinik für Hämatologie, Onkologie und Immunologie, Philipps Universität Marburg und Universitätsklinikum Giessen und Marburg, Standort Marburg, Marburg, Germany.
J Clin Oncol. 2010 Mar 10;28(8):1429-35. doi: 10.1200/JCO.2009.25.5075. Epub 2010 Feb 8.
Imatinib induces sustained remissions in patients with chronic myelogenous leukemia (CML), but fails to eradicate CML stem cells. This is of major concern regarding the issues of cure, long-term imatinib tolerability, and imatinib resistance. We therefore asked whether interferon alfa-2a (IFN) alone could maintain molecular remissions achieved by a prior combination therapy with imatinib and IFN.
Imatinib therapy was stopped in 20 patients who had concomitantly been pretreated with imatinib and IFN for a median of 2.4 years (range, 0.2 to 4.8 years) and 2.5 years (range, 0.2 to 4.9 years), respectively. After imatinib discontinuation, remission status was monitored monthly by quantitative analysis of the peripheral-blood BCR-ABL mRNA levels using real-time polymerase chain reaction. Proteinase-3 expression and proteinase-3-specific cytotoxic T cells (CTLs) were longitudinally measured to assess putative markers of IFN response.
With a median time of 2.4 years after imatinib withdrawal (range, 0.5 to 4.0 years), 15 (75%) of 20 patients remained in remission. The number of patients in complete molecular remission increased under IFN from two patients at baseline to five patients after 2 years. Relapses occurred in five patients within 0.4 years (range, 0.2 to 0.8 years), but patients underwent rescue treatment with imatinib, re-establishing molecular remission. IFN therapy was associated with an increase in the expression of leukemia-associated antigen proteinase 3 and induction of proteinase-3-specific CTLs.
Treatment with IFN enables discontinuation of imatinib in most patients after prior imatinib/IFN combination therapy and may result in improved molecular response. Induction of a proteinase-3-specific CTL response by IFN may contribute to this effect.
伊马替尼可诱导慢性髓性白血病（CML）患者持续缓解，但不能消除 CML 干细胞。这对于治愈、长期伊马替尼耐受性和伊马替尼耐药性等问题非常重要。因此，我们想知道单独使用干扰素-α-2a（IFN）是否可以维持先前联合伊马替尼和 IFN 治疗所获得的分子缓解。
停止了 20 例患者的伊马替尼治疗，这些患者先前分别接受伊马替尼和 IFN 治疗，中位时间为 2.4 年（范围，0.2 至 4.8 年）和 2.5 年（范围，0.2 至 4.9 年）。停止伊马替尼治疗后，通过实时聚合酶链反应定量分析外周血 BCR-ABL mRNA 水平每月监测缓解状态。纵向测量蛋白酶-3 表达和蛋白酶-3 特异性细胞毒性 T 细胞（CTL），以评估 IFN 反应的潜在标志物。
在伊马替尼停药后中位时间为 2.4 年（范围，0.5 至 4.0 年），20 例患者中有 15 例（75%）仍处于缓解状态。在 IFN 治疗下，完全分子缓解的患者数量从基线时的 2 例增加到 2 年后的 5 例。5 例患者在 0.4 年内（范围，0.2 至 0.8 年）复发，但患者接受伊马替尼挽救治疗，重新建立了分子缓解。IFN 治疗与白血病相关抗原蛋白酶-3 的表达增加和蛋白酶-3 特异性 CTL 的诱导相关。
在先前接受伊马替尼/IFN 联合治疗的大多数患者中，IFN 治疗可停用伊马替尼，并可能导致分子缓解改善。IFN 诱导的蛋白酶-3 特异性 CTL 反应可能促成了这一效果。
