Individual outcome prediction for myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia from MDS after allogeneic hematopoietic cell transplantation
Individual outcome prediction for myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia from MDS after allogeneic hematopoietic cell transplantation
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DOI：
10.1007/s00277-017-3027-5
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发表时间：
2017-08-01
影响因子：
3.5
通讯作者：
Thol, Felicitas
中科院分区：
文献类型：
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作者：
Heuser, Michael;Gabdoulline, Razif;Thol, Felicitas
我们将分子数据与因骨髓增生异常综合征 (MDS) 或 MDS 继发性急性髓系白血病 (sAML) 接受同种异体造血细胞移植 (alloHCT) 的患者的可用预后因素进行整合，以评估其对预后的影响。对 304 名患者的 54 个基因的突变进行了测序。我们使用 Cox 多变量模型和竞争风险分析以及内部和交叉验证来确定总体生存 (OS)、累积复发率 (CIR) 和非复发死亡率 (NRM) 的预后因素。在多变量分析中，除了年龄超过 60 岁、缓解状态、IPSS-R 细胞遗传学风险、HCT-CI > 2 和女性供体性别之外，突变的 NRAS、U2AF1、IDH2 和 TP53 和/或复杂核型也是 OS 的重要预后标志物。突变的 NRAS、IDH1、EZH2 和 TP53 和/或复杂的核型是对 CIR 具有预后影响的遗传畸变。没有分子标记与 NRM 风险相关。当通过 Akaike 信息标准进行评估时，包含分子信息可以产生更好的 OS 和 CIR 风险预测模型。内部交叉验证证实了我们综合风险模型的稳健性。总之，我们建议将分子、细胞遗传学以及患者和移植相关的风险因素结合到一个综合风险模型中，以提供 alloHCT 后结果的个性化预测。
We integrated molecular data with available prognostic factors in patients undergoing allogeneic hematopoietic cell transplantation (alloHCT) for myelodysplastic syndrome (MDS) or secondary acute myeloid leukemia (sAML) from MDS to evaluate their impact on prognosis. Three hundred four patients were sequenced for mutations in 54 genes. We used a Cox multivariate model and competing risk analysis with internal and cross validation to identify factors prognostic of overall survival (OS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM). In multivariate analysis, mutated NRAS, U2AF1, IDH2, and TP53 and/or a complex karyotype were significant prognostic markers for OS besides age above 60 years, remission status, IPSS-R cytogenetic risk, HCT-CI > 2 and female donor sex. Mutated NRAS, IDH1, EZH2, and TP53 and/or a complex karyotype were genetic aberrations with prognostic impact on CIR. No molecular markers were associated with the risk of NRM. The inclusion of molecular information results in better risk prediction models for OS and CIR when assessed by the Akaike information criterion. Internal cross validation confirmed the robustness of our comprehensive risk model. In summary, we propose to combine molecular, cytogenetic, and patient- and transplantation-associated risk factors into a comprehensive risk model to provide personalized predictions of outcome after alloHCT.