Leukemia ( IF 12.8 ) Pub Date : 2024-09-10 , DOI: 10.1038/s41375-024-02386-5 Janine Stutterheim 1 , Rachella van der Waarden 1 , Hester A de Groot-Kruseman 1, 2 , Edwin Sonneveld 1, 2 , Valérie de Haas 1, 2 , Rana Dandis 1 , C Ellen van der Schoot 3 , Vincent H J van der Velden 4 , Rob Pieters 1, 2
Measurable residual disease (MRD) is regularly tested at later timepoints after the end of first consolidation (EOC) in children with acute lymphoblastic leukemia (ALL). The question remains whether this is useful for detecting (molecular) relapse. We investigated the clinical relevance of MRD after EOC in intermediate risk patients treated on DCOG-ALL-10 (n = 271) and DCOG-ALL-9 (n = 122), with MRD <0.05% at EOC. EOC MRD-negative patients (n = 178) had excellent outcomes, irrespective of MRD results at later timepoints; 6-year cumulative incidence of relapse (6-y CIR) of 7.4% (95% CI, 3.9%–12.3%) for those with MRD negativity at all later timepoints compared to 3.8% (95% CI, 0.3%–16.8%) for those with one or more later timepoints being positive (p = 0.51). Patients with positive EOC MRD (n = 91) of whom the subsequent timepoints were MRD negative (n = 43), had comparable good outcomes, 6-y CIR of 7.0% (95% CI, 1.8%–17.2%). In contrast, patients being MRD positive at EOC and MRD positive at one or more subsequent timepoints (n = 48) had a higher risk of relapse, 6-y CIR 29.4% (95% CI, 17.2%–42.8%), p < 0.001. These findings were confirmed in the validation cohort of ALL-9 as well as using the updated EuroMRD guidelines. In EOC MRD-negative patients, subsequent MRD measurements can be abandoned. For EOC MRD-positive patients the subsequent MRD measurement might be informative for further risk stratification.
中文翻译:
巩固治疗后可测量的残留病结果对急性淋巴细胞白血病患儿有用吗?
对于急性淋巴细胞白血病 (ALL) 儿童,在首次巩固 (EOC) 结束后的较晚时间点定期检测可测量残留病 (MRD)。问题仍然是这是否有助于检测(分子)复发。我们调查了 EOC 后 MRD 在接受 DCOG-ALL-10 (n = 271) 和 DCOG-ALL-9 (n = 122) 治疗的中等风险患者中的临床相关性,EOC 时 MRD <0.05%。EOC MRD 阴性患者 (n = 178) 无论后期时间点的 MRD 结果如何,都具有良好的结果;在所有较晚时间点 MRD 阴性的患者的 6 年累积复发率 (6-y CIR) 为 7.4% (95% CI,3.9%–12.3%),而 3.8% (95% CI,0.3%–16.8%) 对于一个或多个较晚时间点为阳性的患者 (p = 0.51)。EOC MRD 阳性患者 (n = 91) 且随后时间点为 MRD 阴性 (n = 43),具有相当的良好结果,6 年 CIR 为 7.0% (95% CI,1.8%-17.2%)。相比之下,EOC 时 MRD 阳性且在一个或多个后续时间点 (n = 48) MRD 阳性的患者复发风险更高,6 年 CIR 29.4% (95% CI,17.2%–42.8%),p < 0.001。这些发现在 ALL-9 的验证队列中以及使用更新的 EuroMRD 指南中得到了证实。对于 EOC MRD 阴性患者,可以放弃后续的 MRD 测量。对于 EOC MRD 阳性患者,随后的 MRD 测量可能有助于进一步的风险分层。