Administration of imatinib after allogeneic hematopoietic stem cell transplantation may improve disease-free survival for patients with Philadelphia chromosome-positive acute lymphobla stic leukemia.
Administration of imatinib after allogeneic hematopoietic stem cell transplantation may improve disease-free survival for patients with Philadelphia chromosome-positive acute lymphobla stic leukemia.
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DOI：
10.1186/1756-8722-5-29
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发表时间：
2012-06-08
影响因子：
28.5
通讯作者：
Huang XJ
中科院分区：
文献类型：
--
作者：
Chen H;Liu KY;Xu LP;Liu DH;Chen YH;Zhao XY;Han W;Zhang XH;Wang Y;Zhang YY;Qin YZ;Liu YR;Huang XJ
移植后使用伊马替尼维持治疗已用于费城染色体阳性急性淋巴细胞白血病(Ph + ALL)患者；然而，其疗效尚未得到证实。本研究旨在探讨异基因造血干细胞移植(allo-HCT)后应用伊马替尼预防血液学复发和提高无病生存率(DFS)的安全性和有效性。所有接受异基因红细胞移植的Ph- + 患者均纳入研究。实时定量逆转录聚合酶链式反应(qRT-PCR)检测bcr-abl基因转录水平。如果患者中性粒细胞计数为 >； 1.0 × 109/L，血小板计数为 >； 50.0 × 109/L，或在连续两次检测中bcr-abl转录本水平升高，或初次植入后bcr-abl转录本水平为 ≥ 10-2，则开始伊马替尼治疗。复发后接受伊马替尼治疗的患者被分配到非伊马替尼组。伊马替尼的治疗计划为3-12个 月，直到bcr-abl转录本水平至少连续三个月为阴性或分子完全缓解至少持续3个 月。共有82名患者入选。62例患者在HCT后开始接受伊马替尼治疗。伊马替尼治疗开始的时间中位数为HCT后70 天。3-4级不良事件发生率为17.7%。10例(16.1%)因不良反应终止伊马替尼治疗。在伊马替尼组和非伊马替尼组患者中，5年复发率估计分别为10.2%和33.1%(p = 0.016)，5年无症状生存概率分别为81.5%和33.5%(p = 0.000)，中位随访期分别为31个 月(范围2.5-76 月)和24.5年 月(范围4-72 月)。多因素分析表明，维持性治疗后伊马替尼是影响DFS(p = 0.000，风险比[HR]=4.8)和OS(p = 0.000，HR = 6.2)的独立预后因素。这些结果表明，Ph- + 患者在血细胞移植后接受伊马替尼维持治疗，可以降低复发率，改善生存质量。定量RT-PCR监测bcr-abl可以指导伊马替尼的维持治疗，包括启动时间和治疗持续时间。
Maintenance therapy with imatinib during the post-transplant period has been used for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL); however, its efficacy has not been demonstrated. A study was designed to investigate the safety of imatinib and its efficacy in preventing hematological relapse and improving disease-free survival (DFS) when administered after allogeneic hematopoietic stem cell transplantation (allo-HCT). Patients with Ph + ALL that received allo-HCT were enrolled in the study. Real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to detect BCR-ABL transcript levels. Imatinib therapy was initiated if patient neutrophil counts were > 1.0 × 109/L and platelet counts were > 50.0 × 109/L, or if they displayed either elevated BCR-ABL transcript levels in two consecutive tests, or a BCR-ABL transcript level ≥ 10-2 after initial engraftment. Patients receiving imatinib after relapse were assigned to the non-imatinib group. The imatinib treatment was scheduled for 3–12 months, until BCR-ABL transcript levels were negative at least for three consecutive tests or complete molecular remission was sustained for at least 3 months. A total of 82 patients were enrolled. Sixty-two patients initiated imatinib therapy post-HCT. Imatinib therapy was initiated at a median time of 70 days post-HCT. Grade 3–4 adverse events (AEs) occurred in 17.7% of patients. Ten patients (16.1%) terminated imatinib therapy owing to AEs. Among the patients in imatinib and non-imatinib groups, the estimated 5-year relapse rate was 10.2% and 33.1% (p = 0.016), and the 5-year probability of DFS was 81.5% and 33.5% (p = 0.000) with the median follow-up of 31 months (range, 2.5-76 months) and 24.5 months (range, 4–72 months), respectively. Multivariate analysis identified imatinib maintenance therapy post-HCT as an independent prognostic factor for DFS (p = 0.000, hazard ratio [HR] =4.8) and OS (p = 0.000, HR = 6.2). These results indicate that relapse rate can be reduced and DFS may be improved in Ph + ALL patients with imatinib maintenance therapy after HCT. BCR-ABLmonitoring by qRT-PCR can guide maintenance therapy with imatinib including initiation time and treatment duration after allo-HCT.
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影响因子：
28.5
作者：
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45.3
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