Lene Sofie Granfeldt Østgård, Mette Nørgaard, Eigil Kjeldsen, and Jan Maxwell Nørgaard, Aarhus University Hospital, Aarhus; Henrik Sengeløv, Mette Klarskov Andersen, and Lone Smidstrup Friis, The University Hospital Rigshospitalet, Copenhagen; Inge Høgh Dufva, Herlev University Hospital, Herlev; Claus Werenberg Marcher and Birgitte Preiss, Odense University Hospital, Odense; Marianne Severinsen, Aalborg University Hospital, Aalborg, Denmark; and Bruno C. Medeiros, Stanford University School of Medicine, Stanford, CA.
J Clin Oncol. 2015 Nov 1;33(31):3641-9. doi: 10.1200/JCO.2014.60.0890. Epub 2015 Aug 24.
Secondary 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.
In 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.
Overall, 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).
Our 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.
继发性和治疗相关性急性髓系白血病（分别为 sAML 和 tAML）仍然是治疗方面的挑战。然而，与新发急性髓系白血病（AML）相比，其预后较差是否是由于先前的血液疾病引起，或者是否可以通过核型和/或年龄的差异来解释，目前尚不清楚。
在一项丹麦全国性的、基于人群的研究中，纳入了 3055 例 2000 年至 2013 年期间诊断为 AML 的未经选择的患者，我们比较了 tAML、骨髓增生异常综合征相关的 sAML（MDS-sAML）和非 MDS-sAML（慢性髓单核细胞白血病和骨髓增生性肿瘤）与新发 AML 的发生频率和特征。在仅纳入接受强化治疗的患者中，我们通过逻辑回归分析比较完全缓解的机会，并使用伪值法比较 90 天、1 年和 3 年的死亡相对风险（RR），并根据年龄和核型进行分层。结果以粗率和 95%CI 表示。
总体而言，sAML 和 tAML 的发生率分别为 19.8%和 6.6%。sAML 但不是 tAML 与接受强化治疗的可能性较低相关。在接受强化治疗的患者（n=1567）中，先前的髓系疾病或先前的细胞毒性暴露与较低的完全缓解率和较差的生存相关（MDS-sAML、非 MDS-sAML 和 tAML 的 3 年调整 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，1.03 至 1.32），与新发 AML 相比。在年龄≥60 岁的患者和具有不良核型的患者中，先前的 MDS 或 tAML 并不影响总体预后，而非 MDS-sAML 在年龄和细胞遗传学风险组中与较差的生存相关（不良风险核型：1 年调整 RR，1.47；95%CI，1.23 至 1.76；年龄≥60 岁的患者：1 年调整 RR，1.31；95%CI，1.06 至 1.61）。
我们的结果支持 AML 的新发、sAML 和 tAML 是生物学和预后上不同的 AML 亚型。非 MDS-sAML 患者的预后极差，与年龄和细胞遗传学无关。先前的髓系疾病、年龄和细胞遗传学是影响预后的关键决定因素，应纳入这些患者的治疗建议中。
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