Prognostic significance of MRD and its correlation with arsenic concentration in pediatric acute promyelocytic leukemia: a retrospective study by SCCLG-APL group.
{"title":"Prognostic significance of MRD and its correlation with arsenic concentration in pediatric acute promyelocytic leukemia: a retrospective study by SCCLG-APL group.","authors":"Zhong Fan, Liang-Chun Yang, Yi-Qiao Chen, Wu-Qing Wan, Dun-Hua Zhou, Hui-Rong Mai, Wan-Li Li, Li-Hua Yang, He-Kui Lan, Hui-Qin Chen, Bi-Yun Guo, Zi-Jun Zhen, Ri-Yang Liu, Guo-Hua Chen, Xiao-Qin Feng, Cong Liang, Li-Na Wang, Yu-Li, Jie-Si Luo, Dan-Ping Huang, Xue-Qun Luo, Bin Li, Li-Bin Huang, Xiao-Li Zhang, Yan-Lai Tang","doi":"10.1177/20406207241311774","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Treatment outcomes for acute promyelocytic leukemia (APL) have improved with all-trans-retinoic acid and arsenic trioxide, yet relapse remains a concern, especially in pediatric patients. The prognostic value of minimal residual disease (MRD) post-induction and the impact of arsenic levels during induction on MRD are not fully understood.</p><p><strong>Objectives: </strong>To evaluate the relationship between post-induction MRD levels and relapse-free survival (RFS) in pediatric APL patients, and to investigate the correlation between blood arsenic concentration levels during induction therapy and MRD status.</p><p><strong>Design: </strong>A retrospective analysis of pediatric APL patients enrolled in a clinical trial from September 2011 to July 2020.</p><p><strong>Methods: </strong>We assessed the relationship between RFS and post-induction MRD levels using the log-rank test. The optimal MRD cut-off was determined using the \"surv_cutpoint\" function in the survminer R package. Arsenic concentration levels were monitored in 16 patients on days 7 and 14 of induction therapy, and Spearman correlation was used to analyze the relationship between arsenic concentrations and MRD levels.</p><p><strong>Results: </strong>Among 176 pediatric APL patients, with a median follow-up of 6 years, 4 relapsed. Patients with MRD >3.1% had significantly lower RFS compared to those with MRD ⩽3.1% (94.6% vs 100%, <i>p</i> = 0.023). In addition, a negative correlation was found between blood arsenic concentration levels and post-induction MRD levels. Lower arsenic concentrations were associated with higher MRD levels, with significant correlations observed for trough concentrations (<i>R</i> = -0.666, <i>p</i> = 0.005) and peak concentrations (<i>R</i> = -0.499, <i>p</i> = 0.049) on day 7.</p><p><strong>Conclusion: </strong>Our study highlights the prognostic significance of post-induction MRD assessment in pediatric APL. We also demonstrate a negative correlation between blood arsenic concentration levels and MRD, suggesting that lower arsenic concentrations during induction therapy may contribute to a higher MRD burden. These findings may inform strategies to optimize treatment and improve outcomes in pediatric APL.<b>Trial registration:</b> www.clinicaltrials.gov (NCT02200978).</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"16 ","pages":"20406207241311774"},"PeriodicalIF":3.4000,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707783/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic Advances in Hematology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/20406207241311774","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Treatment outcomes for acute promyelocytic leukemia (APL) have improved with all-trans-retinoic acid and arsenic trioxide, yet relapse remains a concern, especially in pediatric patients. The prognostic value of minimal residual disease (MRD) post-induction and the impact of arsenic levels during induction on MRD are not fully understood.
Objectives: To evaluate the relationship between post-induction MRD levels and relapse-free survival (RFS) in pediatric APL patients, and to investigate the correlation between blood arsenic concentration levels during induction therapy and MRD status.
Design: A retrospective analysis of pediatric APL patients enrolled in a clinical trial from September 2011 to July 2020.
Methods: We assessed the relationship between RFS and post-induction MRD levels using the log-rank test. The optimal MRD cut-off was determined using the "surv_cutpoint" function in the survminer R package. Arsenic concentration levels were monitored in 16 patients on days 7 and 14 of induction therapy, and Spearman correlation was used to analyze the relationship between arsenic concentrations and MRD levels.
Results: Among 176 pediatric APL patients, with a median follow-up of 6 years, 4 relapsed. Patients with MRD >3.1% had significantly lower RFS compared to those with MRD ⩽3.1% (94.6% vs 100%, p = 0.023). In addition, a negative correlation was found between blood arsenic concentration levels and post-induction MRD levels. Lower arsenic concentrations were associated with higher MRD levels, with significant correlations observed for trough concentrations (R = -0.666, p = 0.005) and peak concentrations (R = -0.499, p = 0.049) on day 7.
Conclusion: Our study highlights the prognostic significance of post-induction MRD assessment in pediatric APL. We also demonstrate a negative correlation between blood arsenic concentration levels and MRD, suggesting that lower arsenic concentrations during induction therapy may contribute to a higher MRD burden. These findings may inform strategies to optimize treatment and improve outcomes in pediatric APL.Trial registration: www.clinicaltrials.gov (NCT02200978).
背景：全反式维甲酸和三氧化二砷治疗急性早幼粒细胞白血病（APL）的治疗效果有所改善，但复发仍然是一个问题，特别是在儿科患者中。诱导后微量残留病（MRD）的预后价值以及诱导期间砷水平对MRD的影响尚不完全清楚。目的：探讨小儿APL患者诱导后MRD水平与无复发生存期（RFS）的关系，探讨诱导治疗期间血砷水平与MRD状态的相关性。设计：对2011年9月至2020年7月参加临床试验的儿科APL患者进行回顾性分析。方法：我们使用log-rank检验评估RFS与诱导后MRD水平之间的关系。使用survminer R包中的“surv_cutpoint”函数确定最佳MRD截止值。在诱导治疗第7天和第14天监测16例患者的砷浓度水平，并采用Spearman相关性分析砷浓度与MRD水平之间的关系。结果：176例小儿APL患者中位随访6年，4例复发。MRD≤3.1%的患者RFS明显低于MRD≤3.1%的患者（94.6% vs 100%, p = 0.023）。此外，血砷浓度水平与诱导后MRD水平呈负相关。较低的砷浓度与较高的MRD水平相关，在第7天的低谷浓度（R = -0.666, p = 0.005）和峰值浓度（R = -0.499, p = 0.049）之间存在显著相关性。结论：本研究强调了诱导后MRD评估对小儿APL预后的重要意义。我们还证明了血砷浓度水平与MRD之间的负相关，表明诱导治疗期间较低的砷浓度可能导致较高的MRD负担。这些发现可能为优化治疗策略和改善儿童APL的预后提供信息。试验注册：www.clinicaltrials.gov （NCT02200978）。
期刊介绍：
Therapeutic Advances in Hematology delivers the highest quality peer-reviewed articles, reviews, and scholarly comment on pioneering efforts and innovative studies across all areas of hematology. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in hematology, providing a forum in print and online for publishing the highest quality articles in this area.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
