FUNDALEU, Centro de Internación e Investigación Clínica Angélica Ocampo, Buenos Aires, Argentina.
Clin Lymphoma Myeloma Leuk. 2011 Jun;11(3):280-5. doi: 10.1016/j.clml.2011.03.016. Epub 2011 Apr 20.
Monitoring minimal residual disease (MRD) by real-time quantitative polymerase chain reaction (RT-PCR) in chronic myeloid leukemia (CML) patients is mandatory in the era of tyrosine kinase inhibitors. Achieving a major molecular response (MMR) at 12 and 18 months predicts a better progression and event-free survival.
The objective of this prospective, multicentric study was to evaluate MRD by standardized RT-PCR in 178 patients with chronic-phase CML who were treated with imatinib at different institutions in Argentina and Uruguay and to determine if achievement of a stable MMR (BCR-ABL transcript levels < 0.1%) identifies a low-risk cytogenetic relapse group. The median age of the patients was 50 years, and 55% of them had received imatinib as first-line therapy. BCR-ABL transcript levels were measured after achievement of complete cytogenetic remission (CCyR) and at 6-month intervals.
MMR was detected in 44% patients at the start of the study. This value increased to 79% at month 36 of evaluation. Complete molecular response (CMR) also increased from 24% to 52% of patients. Not achieving a stable MMR determined a higher risk of cytogenetic relapse (9% of MMR patients not achieving an MMR vs. 1% of patients who achieved MMR). Patients with sustained MMR had a significantly better cytogenetic relapse-free survival at 48 months (97% vs. 87%; P = .008) but showed no differences in overall survival. Patients who did not remain in CCyR changed treatment.
A stable MMR is a strong predictor for a durable CCyR. Standardized molecular monitoring could replace cytogenetic analysis once CCyR is obtained. These results emphasize the validity and feasibility of molecular monitoring in all standardized medical centers of the world.
在酪氨酸激酶抑制剂时代，监测慢性髓性白血病（CML）患者的微小残留病（MRD）是强制性的。在 12 个月和 18 个月时达到主要分子反应（MMR）可预测更好的进展和无事件生存。
本前瞻性、多中心研究的目的是评估阿根廷和乌拉圭不同机构使用伊马替尼治疗的 178 例慢性期 CML 患者通过标准化 RT-PCR 检测的 MRD，并确定是否达到稳定的 MMR（BCR-ABL 转录水平<0.1%）可识别低风险细胞遗传学复发组。患者的中位年龄为 50 岁，其中 55%的患者接受伊马替尼作为一线治疗。在达到完全细胞遗传学缓解（CCyR）后和每 6 个月测量 BCR-ABL 转录水平。
在研究开始时，44%的患者检测到 MMR。该值在评估的第 36 个月增加到 79%。完全分子反应（CMR）也从 24%增加到 52%的患者。未达到稳定的 MMR 确定了更高的细胞遗传学复发风险（未达到 MMR 的 MMR 患者为 9%，达到 MMR 的患者为 1%）。持续 MMR 的患者在 48 个月时具有显著更好的细胞遗传学无复发生存（97%对 87%；P=0.008），但总生存无差异。未保持 CCyR 的患者改变了治疗。
稳定的 MMR 是持续 CCyR 的强有力预测因子。一旦获得 CCyR，标准化分子监测可以替代细胞遗传学分析。这些结果强调了分子监测在世界所有标准化医疗中心的有效性和可行性。
