Belarusian Research Centre for Pediatric Oncology and Hematology, Pos. Lesnoe, Minsk 223040, Belarus.
Leuk Res. 2011 Oct;35(10):1312-20. doi: 10.1016/j.leukres.2011.04.013. Epub 2011 May 18.
Detection of minimal residual disease (MRD) during the treatment of acute lymphoblastic leukemia (ALL) by RQ-PCR analysis of clonal Ig/TCR rearrangements is used for risk group stratification in European treatment protocols. In Belarus patients with childhood ALL are treated according to ALL-MB protocols, which do not use MRD-based risk stratification. To evaluate the prognostic significance of MRD for ALL-MB-2002/2008 protocols, MRD was quantified by RQ-PCR in 68 ALL patients at four time points: on day 15, on day 36, before and after maintenance therapy (MT). MRD positivity, as well as quantitative level of MRD were analyzed and compared between patients who stayed in remission and relapsed. Relapse-free survival revealed to be significantly associated with MRD levels at different time points. Unfavorable prognosis was shown for MRD≥10(-3) on day 36 (p<0.001), and any positive MRD before (p<0.001) and after (p=0.001) MT. Multivariate Cox regression analysis proved MRD as independent significant prognosis factor at day 36 (p=0.005) and before MT (p=0.001). We conclude, that MRD quantified by RQ-PCR in children with ALL treated with ALL-MB protocols is feasible and independently associated with outcome. MRD may be a suitable parameter for treatment stratification in MB protocols in future.
采用 RQ-PCR 分析克隆性 Ig/TCR 重排的方法检测急性淋巴细胞白血病 (ALL) 治疗过程中的微小残留病 (MRD)，用于欧洲治疗方案的风险分层。在白俄罗斯，儿童 ALL 患者按照 ALL-MB 方案进行治疗，该方案不采用基于 MRD 的风险分层。为了评估 MRD 对 ALL-MB-2002/2008 方案的预后意义，对 68 例 ALL 患者在四个时间点（第 15 天、第 36 天、维持治疗前和维持治疗后）通过 RQ-PCR 定量检测 MRD。分析并比较了缓解和复发患者之间 MRD 阳性和 MRD 定量水平。无复发生存率与不同时间点的 MRD 水平显著相关。第 36 天 MRD≥10(-3)（p<0.001）以及维持治疗前（p<0.001）和维持治疗后（p=0.001）任何阳性 MRD 与不良预后相关。多变量 Cox 回归分析证明第 36 天（p=0.005）和维持治疗前（p=0.001）MRD 是独立的显著预后因素。我们得出结论，用 ALL-MB 方案治疗的 ALL 儿童中通过 RQ-PCR 定量检测的 MRD 是可行的，并且与结局独立相关。MRD 可能是未来 MB 方案中治疗分层的合适参数。
