The Extent of Minimal Residual Disease Reduction After the First 4-Week Imatinib Therapy Determines Outcome of Allogeneic Stem Cell Transplantation in Adults With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia
The Extent of Minimal Residual Disease Reduction After the First 4-Week Imatinib Therapy Determines Outcome of Allogeneic Stem Cell Transplantation in Adults With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia
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DOI：
10.1002/cncr.24026
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发表时间：
2009-02-01
期刊：
影响因子：
6.2
通讯作者：
Kim, Chun-Choo
中科院分区：
文献类型：
--
作者：
Lee, Seok;Kim, Yoo-Jin;Kim, Chun-Choo
背景技术背景：此前，作者证明了伊马替尼对费城染色体阳性急性淋巴细胞白血病（Ph阳性ALL）成人异基因干细胞移植结局的积极影响。在这里，作者分析了影响移植结果的风险因素，他们特别关注每个治疗阶段微小残留病水平的预后相关性。方法：本研究入组了52例伊马替尼治疗后完成异基因干细胞移植的新诊断Ph阳性ALL患者。对于微小残留病监测，通过实时定量聚合酶链反应测定分析了548份骨髓样本。研究结果：在第一个4周伊马替尼治疗后，11例患者（21.2%）达到分子缓解，其余41例患者的BCR-ABL转录水平较基线值降低（中位数，3.21 log），在此阶段实现BCR-ABL转录水平至少降低3 log的频率为36例（69.2%）。52例患者中有48例（92.3%）在首次完全缓解期间接受了干细胞移植。干细胞移植后中位随访49个月，4年复发率和无病生存率分别为21.2%和69.8%。伊马替尼治疗前4周后BCR-ABL转录水平降低至少3 log被确定为复发率较低（12.1% vs 45.1%，P = 0.011）和无病生存率较好（82.1% vs 41.7%，P = 0.009）的最有力预测因素。结论：前瞻性评估伊马替尼治疗前4周后微小残留病减少的程度，可使作者确定复发风险高的Ph阳性ALL移植亚组。Cancer 2009;115：561-70. (c)2008美国癌症协会
BACKGROUND: Previously, the authors demonstrated the positive impact of imatinib on the outcome of allogeneic stem cell transplantation in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). Here, the authors analyzed for risk factors that affect transplantation outcome, and they focused particularly on the prognostic relevance of minimal residual disease level at each treatment stage. METHODS: Fifty-two patients with newly diagnosed Ph-positive ALL who completed allogeneic stem cell transplantation following imatinib therapy were enrolled in this study. For minimal residual disease monitoring, 548 marrow samples were analyzed by a real-time quantitative polymerase chain reaction assay. RESULTS: After the first 4-week imatinib therapy, 11 patients (21.2%) achieved molecular remission, and the remaining 41 patients had a reduction in BCR-ABL transcript levels (median, 3.21 log) from baseline value, The frequency of achieving a reduction in BCR-ABL transcript levels of at least 3 log at this stage was 36 (69.2%). Forty-eight (92.3%) of the 52 patients received stem cell transplantation during first complete remission. With a median follow-up of 49 months after stem cell transplantation, the 4-year relapse rate and disease-free survival rate were 21.2% and 69.8%, respectively. A reduction in BCR-ABL transcript levels of at least 3 log after the first 4-week imatinib therapy was identified as the most powerful predictor of lower relapse (12.1% vs 45.1%, P = .011) and better disease-free survival (82.1% vs 41.7%, P = .009) rates. CONCLUSIONS: Prospective assessment of the extent of minimal residual disease reduction after the first 4-week imatinib therapy may allow the authors to identify subgroups of Ph-positive ALL transplants at high risk of relapse. Cancer 2009;115:561-70. (c) 2008 American Cancer Society.