Kaygusuz Atagunduz Isik, Toptas Tayfur, Deniz Rabia, Kara Osman, Eser Ali, Sezgin Aslıhan, Ozgumus Toluy, Gecgel Fatma, Firatli Tuglular Tulin
Department of Hematology, Marmara University Hospital, Istanbul, Turkey.
Department of Hematology, Marmara University Hospital, Istanbul, Turkey.
Clin Lymphoma Myeloma Leuk. 2017 Feb;17(2):120-125. doi: 10.1016/j.clml.2016.09.006. Epub 2016 Sep 17.
The prognostic significance of complete cytogenetic response (CCyR) is well defined in patients with chronic phase chronic myeloid leukemia treated with imatinib as first-line therapy. However, the effect on outcomes of obtaining molecular response itself and the depth of it is not clear. In this study we aimed to determine the frequency of complete molecular response (CMR) during long-term follow-up and the clinical significance of CMR on patient outcomes and survival.
We retrospectively evaluated the files of 178 chronic phase chronic myeloid leukemia patients using imatinib therapy. Forty-seven patients with missing data were excluded from the study and the assessment was done in 131 patients. CMR was defined as undetectable BCR-ABL transcripts using real-time quantitative polymerase chain reaction with a sensitivity level of ≥ 10 in 2 consecutive analyses at least 3 months apart. Cytogenetic and molecular monitoring during treatment was performed according to the European LeukemiaNet recommendations criteria. Our primary objective was to analyze the association of deeper molecular response with differences in progression-free survival (PFS).
Eighty-eight patients (67%) achieved CMR at any time in a median of 65 months of follow-up. The rate of CMR was higher in patients who achieved CCyR at 12 months and major molecular response (MMR) at 18 months. Fewer events occurred in the CMR group than the MMR group (26.1% vs. 50.0%). Overall survival was not different in both groups. CMR was associated with longer PFS with borderline significance.
Prolonged imatinib therapy helps to achieve a deeper molecular response in the long-term. Achieving deeper molecular response at any time positively affects maintaining the cytogenetic and molecular responses, and decreases the transformation to accelerated and/or blastic phase. The slight prolongation in PFS did not reach statistical significance.
在接受伊马替尼一线治疗的慢性期慢性髓性白血病患者中，完全细胞遗传学缓解（CCyR）的预后意义已得到明确界定。然而，获得分子学缓解本身及其深度对预后的影响尚不清楚。在本研究中，我们旨在确定长期随访期间完全分子学缓解（CMR）的发生率以及CMR对患者预后和生存的临床意义。
我们回顾性评估了178例接受伊马替尼治疗的慢性期慢性髓性白血病患者的病历。47例有缺失数据的患者被排除在研究之外，对131例患者进行了评估。CMR定义为使用实时定量聚合酶链反应检测不到BCR-ABL转录本，敏感性水平≥10，且至少相隔3个月进行连续2次分析。治疗期间的细胞遗传学和分子监测按照欧洲白血病网推荐标准进行。我们的主要目标是分析更深层次分子学缓解与无进展生存期（PFS）差异之间的关联。
在中位65个月的随访中，88例患者（67%）在任何时间达到CMR。在12个月时达到CCyR且在18个月时达到主要分子学缓解（MMR）的患者中，CMR发生率更高。CMR组发生的事件少于MMR组（26.1%对50.0%）。两组的总生存期无差异。CMR与更长的PFS相关，具有临界显著性。
长期伊马替尼治疗有助于长期实现更深层次的分子学缓解。在任何时间实现更深层次的分子学缓解对维持细胞遗传学和分子学缓解有积极影响，并减少向加速期和/或急变期的转化。PFS的轻微延长未达到统计学显著性。
