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基于年龄、绝对中性粒细胞计数和绝对淋巴细胞计数的全球适用的原发性血小板增多症“三重 A”风险模型。

A globally applicable "triple A" risk model for essential thrombocythemia based on Age, Absolute neutrophil count, and Absolute lymphocyte count.

机构信息

Divisions of Hematology and Hematopathology, Mayo Clinic, Rochester, Minnesota, USA.

Department of Experimental and Clinical Medicine, CRIMM, Center Research, and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy.

出版信息

Am J Hematol. 2023 Dec;98(12):1829-1837. doi: 10.1002/ajh.27079. Epub 2023 Sep 4.

Abstract

We examined the individual prognostic contribution of absolute neutrophil (ANC), lymphocyte (ALC), and monocyte (AMC) counts, on overall (OS), leukemia-free (LFS), and myelofibrosis-free (MFFS) survival in essential thrombocythemia (ET). Informative cases (N = 598; median age 59 years; females 62%) were retrospectively accrued from a Mayo Clinic database: JAK2 59%, CALR 27%, triple-negative 11%, and MPL 3%; international prognostic scoring system for ET (IPSET) risk high 21%, intermediate 42%, and low 37%; 7% (37/515) had abnormal karyotype and 10% (21/205) adverse mutations (SF3B1/SRSF2/U2AF1/TP53). At median 8.4 years, 163 (27%) deaths, 71 (12%) fibrotic, and 20 (3%) leukemic transformations were recorded. Multivariable analysis resulted in HR (95% CI) of 16.5 (9.9-27.4) for age > 70 years, 3.7 (2.3-6.0) for age 50-70 years, 2.4 (1.7-3.3) for ANC ≥8 × 10 /L, and 1.9 (1.4-2.6) for ALC <1.7 × 10 /L. The corresponding HR-based scores were 4, 2, 1, and 1, resulting in an new 4-tiered AgeAncAlc (AAA; triple A) risk model: high (5-6 points; median survival 8 years; HR 30.1, 95% CI 17.6-54), intermediate-2 (4 points; median 13.5 years; HR 12.7, 95% CI 7.1-23.0), intermediate-1 (2-3 points; median 20.7 years; HR 3.8, 95% CI 2.3-6.4) and low (0-1 points; median 47 years). The AAA model (Akaike Information Criterion [AIC] 621) performed better than IPSET (AIC 647) and was subsequently validated by an external University of Florence ET cohort (N = 485). None of the AAA variables predicted LFS while ALC <1.7 × 10 /L was associated with inferior MFFS (p = .01). Adverse mutations (p < .01) and karyotype (p < .01) displayed additional prognostic value without disqualifying the prognostic integrity of the AAA model. This study proposes a simple and globally applicable survival model for ET, which can be used as a platform for further molecular refinement. This study also suggests a potential role for immune-related biomarkers, as a prognostic tool in myeloproliferative neoplasms.

摘要

我们研究了绝对中性粒细胞(ANC)、淋巴细胞(ALC)和单核细胞(AMC)计数对原发性血小板增多症(ET)患者总生存期(OS)、白血病无进展生存期(LFS)和骨髓纤维化无进展生存期(MFFS)的个体预后贡献。从梅奥诊所数据库中回顾性收集了有意义的病例(N=598;中位年龄 59 岁;女性占 62%):JAK2 59%、CALR 27%、三阴性 11%、MPL 3%;国际预后评分系统(IPSET)高危 21%、中危 42%、低危 37%;7%(37/515)存在异常核型,10%(21/205)存在不良突变(SF3B1/SRSF2/U2AF1/TP53)。中位随访 8.4 年后,记录到 163 例(27%)死亡,71 例(12%)纤维化和 20 例(3%)白血病转化。多变量分析显示,年龄>70 岁(HR 95%CI 16.5[9.9-27.4])、50-70 岁(HR 3.7[2.3-6.0])、ANC≥8×10 /L(HR 2.4[1.7-3.3])和 ALC<1.7×10 /L(HR 1.9[1.4-2.6])的风险较高。相应的 HR 评分分别为 4、2、1 和 1,由此产生了新的 4 级 AgeAncAlc(AAA;三重 A)风险模型:高危(5-6 分;中位生存期 8 年;HR 30.1,95%CI 17.6-54)、中危-2(4 分;中位生存期 13.5 年;HR 12.7,95%CI 7.1-23.0)、中危-1(2-3 分;中位生存期 20.7 年;HR 3.8,95%CI 2.3-6.4)和低危(0-1 分;中位生存期 47 年)。AAA 模型(赤池信息量准则[AIC]621)的表现优于 IPSET(AIC647),随后通过佛罗伦萨大学的一个 ET 队列(N=485)进行了验证。AAA 模型中的任何一个变量都不能预测 LFS,而 ALC<1.7×10 /L 与较差的 MFFS 相关(p=0.01)。不良突变(p<0.01)和核型(p<0.01)显示了额外的预后价值,而不会影响 AAA 模型的预后完整性。这项研究提出了一个简单的、适用于全球的 ET 生存模型,可以作为进一步分子细化的平台。该研究还表明,免疫相关生物标志物可能作为骨髓增殖性肿瘤的一种预后工具。

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