Department of Pediatrics, Ribeirão Preto Medicine School, University of Sao Paulo, Ribeirão Preto, Brazil.
Leuk Lymphoma. 2012 Jan;53(1):89-95. doi: 10.3109/10428194.2011.606939. Epub 2011 Aug 24.
We analyzed cerebrospinal fluid (CSF) samples from 65 consecutive children with acute lymphoblastic leukemia (ALL) treated according to two different treatment protocols (GBTLI-ALL-93 and -99) with no puncture accident for minimal residual disease (MRD) in the central nervous system (CNS). Minimal residual disease was detected by polymerase chain reaction (PCR) with homo/heteroduplex analysis using consensus primers to IgH and TCR genes. MRD in the CSF at diagnosis was detected by PCR in 46.8% of children with no puncture accident or morphological involvement. In patients treated with GBTLI-ALL-93 a significantly lower 5-year event-free survival (EFS) was demonstrated for those with CSF involvement, in univariate (p = 0.01) and multivariate (p = 0.04) analysis. This observation was not true for patients treated with the more intensive protocol GBTLI-ALL-99 (p = 0.81). These findings suggest that MRD detection in the CSF is a common event in children with ALL. Treatment intensification provided by the GBTLI-ALL-99 apparently overcomes the detrimental effect of CNS minimal residual disease at diagnosis.
我们分析了 65 例连续急性淋巴细胞白血病（ALL）患儿的脑脊液（CSF）样本，这些患儿按照两种不同的治疗方案（GBTLI-ALL-93 和 -99）治疗，且无穿刺事故发生以检测中枢神经系统（CNS）中的微小残留病（MRD）。微小残留病通过聚合酶链反应（PCR）检测，使用共识引物对 IgH 和 TCR 基因进行同/异双链分析。在无穿刺事故或形态学受累的患儿中，46.8%的患儿在诊断时通过 PCR 检测到 CSF 中的 MRD。在接受 GBTLI-ALL-93 治疗的患者中，CSF 受累患者的 5 年无事件生存率（EFS）显著降低，在单变量（p=0.01）和多变量（p=0.04）分析中均如此。对于接受更强化方案 GBTLI-ALL-99 治疗的患者而言并非如此（p=0.81）。这些发现表明，CSF 中 MRD 的检测在 ALL 患儿中是一种常见事件。GBTLI-ALL-99 提供的治疗强化显然克服了诊断时 CNS 微小残留病的不良影响。
