Epidemiology and Clinical Significance of Secondary and Therapy-Related Acute Myeloid Leukemia: A National Population-Based Cohort Study
Epidemiology and Clinical Significance of Secondary and Therapy-Related Acute Myeloid Leukemia: A National Population-Based Cohort Study
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DOI：
10.1200/jco.2014.60.0890
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发表时间：
2015-11-01
影响因子：
45.3
通讯作者：
Norgaard, Jan Maxwell
中科院分区：
文献类型：
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作者：
Ostgard, Lene Sofie Granfeldt;Medeiros, Bruno C.;Norgaard, Jan Maxwell
目的继发性和治疗相关性急性髓系白血病（sAML和tAML）仍然是治疗的挑战。然而，目前尚不清楚他们与原发性急性髓细胞白血病（AML）相比的劣化结果是否由于先前的血液学疾病而变化，或者可以通过核型和/或年龄的差异来解释。患者和方法在一项基于丹麦全国人群的研究中，对2000年至2013年诊断为AML的3，055例AML患者进行了研究，我们比较了tAML的频率和特征，骨髓增生异常综合征（MDS）-sAML和非MDS-sAML（慢性粒单核细胞白血病和骨髓增生性瘤形成）与新生AML。仅限于强化治疗患者，我们通过logistic回归分析比较完全缓解的机会，并使用伪值方法比较90天、1年和3年时死亡的相对风险（RR），总体和按年龄和核型分层。结果给予粗和调整95%CIs.ResultsAML和tAML的频率分别为19.8%和6.6%，分别。sAML，而不是tAML，与接受强化治疗的可能性低相关。在强化治疗患者中（n = 1，567），既往有髓系疾病或细胞毒暴露与完全缓解率降低和生存率降低相关（MDS-sAML、非MDS-sAML和tAML的3年校正RR：RR，1.14; 95% CI，1.02至1.32; RR，1.27; 95% CI，1.16至1.34; RR，1.16; 95% CI，分别为1.03 - 1.32）。在年龄60岁和核型不良的患者中，既往MDS或tAML不影响总体结局，而非MDS-sAML与年龄和细胞遗传学风险组的生存率较低相关（不良风险细胞遗传学：1年校正RR，1.47; 95% CI，1.23 - 1.76; 60岁患者：1年校正RR，1.31; 95%CI为1.06 ~ 1.61）。结论原发性AML、sAML和tAML在生物学和病理学上是不同的AML亚型。非MDS-sAML患者的结局令人沮丧，与年龄和细胞遗传学无关。既往骨髓疾病、年龄和细胞遗传学是决定预后的关键因素，应纳入这些患者的治疗建议。(C)2015年美国临床肿瘤学会
PurposeSecondary and therapy-related acute myeloid leukemia (sAML and tAML, respectively) remain therapeutic challenges. Still, it is unclear whether their inferior outcome compared with de novo acute myeloid leukemia (AML) varies as a result of previous hematologic disease or can be explained by differences in karyotype and/or age.Patients and MethodsIn a Danish national population-based study of 3,055 unselected patients with AML diagnosed from 2000 to 2013, we compared the frequencies and characteristics of tAML, myelodysplastic syndrome (MDS)-sAML, and non-MDS-sAML (chronic myelomonocytic leukemia and myeloproliferative neoplasia) versus de novo AML. Limited to intensive therapy patients, we compared chance of complete remission by logistic regression analysis and used a pseudo-value approach to compare relative risk (RR) of death at 90 days, 1 year, and 3 years, overall and stratified by age and karyotype. Results were given crude and adjusted with 95% CIs.ResultsOverall, frequencies of sAML and tAML were 19.8% and 6.6%, respectively. sAML, but not tAML, was associated with low likelihood of receiving intensive treatment. Among intensive therapy patients (n = 1,567), antecedent myeloid disorder or prior cytotoxic exposure was associated with decreased complete remission rates and inferior survival (3-year adjusted RR for MDS-sAML, non-MDS-sAML, and tAML: RR, 1.14; 95% CI, 1.02 to 1.32; RR, 1.27; 95% CI, 1.16 to 1.34; and RR, 1.16; 95% CI, 1.03 to 1.32, respectively) compared with de novo AML. Among patients 60 years old and patients with adverse karyotype, previous MDS or tAML did not impact overall outcomes, whereas non-MDS-sAML was associated with inferior survival across age and cytogenetic risk groups (adverse risk cytogenetics: 1-year adjusted RR, 1.47; 95% CI, 1.23 to 1.76; patients 60 years old: 1-year adjusted RR, 1.31; 95% CI, 1.06 to 1.61).ConclusionOur results support that de novo AML, sAML, and tAML are biologically and prognostically distinct subtypes of AML. Patients with non-MDS-sAML have dismal outcomes, independent of age and cytogenetics. Previous myeloid disorder, age, and cytogenetics are crucial determinants of outcomes and should be integrated in treatment recommendations for these patients. (C) 2015 by American Society of Clinical Oncology