Sustained complete molecular remissions after treatment with imatinib-mesylate in patients with failure after allogeneic stem cell transplantation for chronic myelogenous leukemia:: Results of a prospective phase II open-label multicenter study
Sustained complete molecular remissions after treatment with imatinib-mesylate in patients with failure after allogeneic stem cell transplantation for chronic myelogenous leukemia:: Results of a prospective phase II open-label multicenter study
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DOI：
10.1200/jco.2005.01.3110
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发表时间：
2005-10-20
影响因子：
45.3
通讯作者：
Fischer, T
中科院分区：
文献类型：
--
作者：
Hess, G;Bunjes, D;Fischer, T
目的在应用BCR-ABL酪氨酸激酶抑制剂进行慢性粒细胞白血病（CML）分子治疗的时代，BCR-ABL的分子终点，特别是定量聚合酶链反应（PCR）在监测疗效方面的作用已被广泛接受。因此，我们已经设计了一个前瞻性的第二阶段试验在CML，这是第一次，评估的可行性和安全性的分子终点作为替代标记，通过分层治疗算法内的多中心trial.Patients和方法作为一个临床模型，我们采用了微小残留病（MRD）发现在异基因干细胞移植（SCT）后复发的CML。44例患者入组并接受BCR-ABL酪氨酸激酶抑制剂伊马替尼（IM），起始剂量为400 mg/d。然后决定IM或剂量递增到800 mg/d，最后，在应用供体淋巴细胞infussions.Results 70%的患者实现了完全的分子反应（CMR），定义为巢式PCR阴性的BCR-ABL在三个连续的样品中的质量的分子反应。有趣的是，在10例停止IM的患者中，有4例即使在IM停止后，CMR也是持久的，中位随访时间为494天。这表明在一个子集的patients.Conclusion长期肿瘤控制的可能性表明，IM治疗策略是耐受性良好，在MRD后，异基因SCT是非常有效的。此外，本研究表明，在多中心试验中评价分子终点可以是临床决策的安全有效工具。
Purpose In the era of molecular therapy of chronic myelogenous leukemia (CML) applying BCR-ABL tyrosine kinase inhibitors, the usefulness of molecular end points, in particular, quantitative polymerase chain reaction (PCR) for BCR-ABL in monitoring responses has been broadly accepted. Therefore, we have designed a prospective phase II trial in CML, which, for the first time, evaluated the feasibility and safety of molecular end points as surrogate markers to guide through a stratified treatment algorithm within a multicenter trial.Patients and Methods As a clinical model, we adopted minimal residual disease (MRD) found in relapse after allogeneic stem cell transplantation (SCT) in CML. Forty-four patients were enrolled and received the BCR-ABL tyrosine kinase inhibitor imatinib (IM) at a starting dose of 400 mg/d. The quality of molecular responses achieved then decided on discontinuation of IM or dose escalation up to 800 mg/d, and finally, on application of donor lymphocyte infusions.Results Seventy percent of patients achieved a complete molecular response (CMR), defined as nested PCR-negativity for BCR-ABL in three consecutive samples. Interestingly, in four out of 10 patients who discontinued IM, CMR was durable even after cessation of IM with a median follow-up of 494 days. This suggests the possibility of long-term tumor control in a subset of patients.Conclusion The treatment strategy showed that IM treatment was well-tolerated and highly efficacious in MRD after allogeneic SCT. Moreover, this study demonstrated that evaluation of a molecular end point within a multicenter trial can be a safe and effective tool for clinical decision making.