Reduced Morbidity and Mortality in Survivors of Childhood Acute Lymphoblastic Leukemia: A Report From the Childhood Cancer Survivor Study
Reduced Morbidity and Mortality in Survivors of Childhood Acute Lymphoblastic Leukemia: A Report From the Childhood Cancer Survivor Study
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DOI：
10.1200/jco.20.00493
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发表时间：
2020-10-10
影响因子：
45.3
通讯作者：
Nathan, Paul C.
中科院分区：
文献类型：
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作者：
Dixon, Stephanie B.;Chen, Yan;Nathan, Paul C.
根据临床和生物学特征对治疗进行调整的风险分层治疗已将儿童急性淋巴细胞白血病（ALL）的5年总生存率提高到90%，但其对长期毒性的影响尚不清楚。（包括癌症治疗的晚期效应）、随后的恶性肿瘤（SMN）、慢性健康状况和神经认知结局，1970年至1999年诊断的148例儿童ALL幸存者（中位年龄27.9岁;范围5.9-61.9岁）。治疗组合和治疗强度定义了6组：20世纪70年代样（70 s）、标准或高风险20世纪80年代样（80 sSR，80 sHR）和20世纪90年代样（90 sSR，90 sHR）以及复发/移植（R/BMT）。比较了治疗组和美国人群的累积发病率、标准化死亡率和标准化发病率，总的来说，20年全因晚期死亡率为6.6%（95%CI，6.0 - 7.1）。90 sSR和90 sHR的健康相关晚期死亡率低于70岁（率比[95% CI]：90 sSR，0.2 [0.1 - 0.4]; 90 sHR，0.3 [0.1 - 0.7]），与美国人群相当（标准化死亡率[95% CI]：90 sSR，1.3 [0.8 - 2.0]; 90 sHR，1.7 [0.7 - 3.5]）。与70岁以上人群相比，90岁以下人群的SMN发生率较低（率比[95% CI]，0.3 [0.1 - 0.6]），与美国人群无差异（标准化发病率比[95% CI]，1.0 [0.6 - 1.6]）。90年代SR组的严重慢性健康状况比70年代少（20年累积发生率[95% CI]，11.0% [9.7%-12.3%] vs 22.5% [19.4%-25.5%]）和记忆受损的患病率较低（患病率[95%CI]，0.7 [0.6 - 0.9]）和任务效率（0.5 [0.4 - 0.7]）。结论风险分层治疗降低了以90 sSR为代表的标准风险ALL当代存活者的晚期发病率和死亡率。当代标准风险儿童ALL 5年存活者的健康相关晚期死亡率和SMN风险与一般人群相当。
PURPOSERisk-stratified therapy, which modifies treatment on the basis of clinical and biologic features, has improved 5-year overall survival of childhood acute lymphoblastic leukemia (ALL) to 90%, but its impact on long-term toxicity remains unknown.METHODSWe assessed all-cause and health-related late mortality (including late effects of cancer therapy), subsequent malignant neoplasms (SMNs), chronic health conditions, and neurocognitive outcomes among 6,148 survivors of childhood ALL (median age, 27.9 years; range, 5.9-61.9 years) diagnosed between 1970 and 1999. Therapy combinations and treatment intensity defined 6 groups: 1970s-like (70s), standard- or high-risk 1980s-like (80sSR, 80sHR) and 1990s-like (90sSR, 90sHR), and relapse/transplantation (R/BMT). Cumulative incidence, standardized mortality ratios, and standardized incidence ratios were compared between treatment groups and with the US population.RESULTSOverall, 20-year all-cause late mortality was 6.6% (95% CI, 6.0 to 7.1). Compared with 70s, 90sSR and 90sHR experienced lower health-related late mortality (rate ratio [95% CI]: 90sSR, 0.2 [0.1 to 0.4]; 90sHR, 0.3 [0.1 to 0.7]), comparable to the US population (standardized mortality ratio [95% CI]: 90sSR, 1.3 [0.8 to 2.0]; 90sHR, 1.7 [0.7 to 3.5]). Compared with 70s, 90sSR had a lower rate of SMN (rate ratio [95% CI], 0.3 [0.1 to 0.6]) that was not different from that of the US population (standardized incidence ratio [95% CI], 1.0 [0.6 to 1.6]). The 90sSR group had fewer severe chronic health conditions than the 70s (20-year cumulative incidence [95% CI], 11.0% [9.7% to 12.3%] v 22.5% [19.4% to 25.5%]) and a lower prevalence of impaired memory (prevalence ratio [95% CI], 0.7 [0.6 to 0.9]) and task efficiency (0.5 [0.4 to 0.7]).CONCLUSIONRisk-stratified therapy has reduced late morbidity and mortality among contemporary survivors of standard-risk ALL, represented by 90sSR. Health-related late mortality and SMN risks among 5-year survivors of contemporary, standard-risk childhood ALL are comparable to the general population.