Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia
Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia
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DOI：
10.1182/blood-2005-07-2708
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发表时间：
2006-02-01
期刊：
影响因子：
20.3
通讯作者：
Kneba, M
中科院分区：
文献类型：
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作者：
Brüggemann, M;Raff, T;Kneba, M
由于不存在不良预后因素，成年急性淋巴细胞白血病 (ALL) 患者被分为标准风险 (SR) 组，其中 40% 至 55% 的病例会出现复发。为了确定适合 SR ALL 进一步治疗分层的补充标志物，我们评估了微小残留病 (MRD) 的预测价值，并通过定量聚合酶链反应 (PCR) 在治疗第一年的最多 9 个时间点对 196 名严格定义的 SR ALL 患者进行了前瞻性监测。 MRD 阳性频率从早期诱导期间的 88% 下降到第 52 周时的 13%。MRD 可预测不同随访时间点的复发。结合不同时间点的 MRD 信息可以定义 3 个风险组 (P < .001)：在第 11 天和第 24 天 MRD 快速下降至低于 10(-4) 或低于检测限的患者中，有 10% 被归类为低风险，且 3 年复发率 (FIR) 为 0%。直到第 16 周 MRD 为 10(-4) 或更高的 23% 的子集形成高风险组，3 年 RR 为 94%（95% 置信区间 [CI] 83%-100%）。其余 RR 为 47%（31%-63%）的患者代表中危组。因此，治疗期间的 MRD 量化可识别出同质 SR ALL 人群中可能受益于个体化治疗的预后亚组。
Adult patients with acute lymphoblastic leukemia (ALL) who are stratified into the standard-risk (SR) group due to the absence of adverse prognostic factors relapse in 40% to 55% of the cases. To identify complementary markers suitable for further treatment stratification in SR ALL, we evaluated the predictive value of minimal residual disease (MRD) and prospectively monitored MRD in 196 strictly defined SR ALL patients at up to 9 time points in the first year of treatment by quantitative polymerase chain reaction (PCR). Frequency of MRD positivity decreased from 88% during early induction to 13% at week 52. MRD was predictive for relapse at various follow-up time points. Combined MRD information from different time points allowed definition of 3 risk groups (P < .001): 10% of patients with a rapid MRD decline to lower than 10(-4) or below detection limit at day 11 and day 24 were classified as low risk and had a 3-year relapse rate (FIR) of 0%. A subset of 23% with an MRD of 10(-4) or higher until week 16 formed the high-risk group, with a 3-year RR of 94% (95% confidence interval [CI] 83%-100%). The remaining patients whose RR was 47% (31%-63%) represented the intermediate-risk group. Thus, MRD quantification during treatment identified prognostic subgroups within the otherwise homogeneous SR ALL population who may benefit from individualized treatment.