Koffi Kouassi Gustave, Bognini Sara Akou, Silué Dohoma Alexis, Kamara Ismael, Kouakou Ines, N'dhatz Emeraude, Kouakou Boidy, Nanho Danho Clotaire, Okou David Tea
Department of Hematology Teaching Hospital, Centre Hospitalier Universitaire de Yopougon, 21 BP 632, Abidjan 21, Ivory Coast.
Department of Genetics, Clinic Saint George, Abidjan, Ivory Coast.
Adv Hematol. 2024 Dec 11;2024:4576455. doi: 10.1155/2024/4576455. eCollection 2024.
The present study aimed to evaluate for the first time, the early molecular response (EMR) to imatinib at 3 months for patients with chronic myeloid leukemia and to determine the predictive factors that influence poor outcome and response. 60 newly diagnosed CML patients were enrolled from May 2018 to June 2023. They received imatinib and prospectively underwent a molecular evaluation. Their EMR was assessed using a RT-qPCR method and expressed as the IS transcript level at 3 months. Potential factors impacting the EMR were identified using the Cox proportional hazard regression models. The effects of an EMR on the cumulative incidence of a deep molecular response (DMR) were also evaluated. Out of the 60 CML patients recruited, 29 (48%) achieved an optimal response with TKI therapy after 3 months. The cumulative rate of molecular response was 16 (36%) for a major molecular response (MMR), 10 (23%) for MR4, 8 (18%) for MR4.5, and 6 (14%) for MR5, while 4 (9%) showed indetectable transcript. In addition, as 26 (90%) of patients with optimal response at 3 months showed a DMR, we determined that an optimal response to TKI at 3 months was significantly correlated with a DMR. We also identified through multivariate analysis that seven independent risk factors significantly influenced an EMR to TKI. These factors included male, late diagnosis, advanced performance status, the presence of splenomegaly, high-ELTS risk groups, a domain mutation, and complete hematologic response after more than 30 days. Our study demonstrates that an EMR at 3 months has a predictive value for a DMR. In addition, a MMR and a DMR can be predicted using a combination of parameters that either have a significant impact on the optimal response, or that can serve as prognostic indicators for molecular response, especially in low-income countries, where molecular assessment and monitoring are not available or possible.
本研究旨在首次评估慢性髓性白血病患者在3个月时对伊马替尼的早期分子反应（EMR），并确定影响不良预后和反应的预测因素。2018年5月至2023年6月招募了60例新诊断的慢性髓性白血病患者。他们接受伊马替尼治疗并前瞻性地进行分子评估。使用RT-qPCR方法评估他们的EMR，并表示为3个月时的IS转录水平。使用Cox比例风险回归模型确定影响EMR的潜在因素。还评估了EMR对深度分子反应（DMR）累积发生率的影响。在招募的60例慢性髓性白血病患者中，29例（48%）在3个月后通过酪氨酸激酶抑制剂（TKI）治疗获得了最佳反应。主要分子反应（MMR）的分子反应累积率为16例（36%），MR4为10例（23%），MR4.5为8例（18%），MR5为6例（14%），而4例（9%）显示转录本不可检测。此外，由于3个月时26例（90%）获得最佳反应的患者显示出DMR，我们确定3个月时对TKI的最佳反应与DMR显著相关。我们还通过多变量分析确定了七个独立风险因素对TKI的EMR有显著影响。这些因素包括男性、诊断延迟、较高的体能状态、脾肿大、ELTS高风险组、一个结构域突变以及超过30天后的完全血液学反应。我们的研究表明，3个月时的EMR对DMR具有预测价值。此外，可以使用对最佳反应有显著影响或可作为分子反应预后指标的参数组合来预测MMR和DMR，特别是在无法进行分子评估和监测的低收入国家。
