Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis
Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis
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DOI：
10.1182/blood-2014-05-579136
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发表时间：
2014-10-16
期刊：
影响因子：
20.3
通讯作者：
Vannucchi, Alessandro M.
中科院分区：
文献类型：
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作者：
Tefferi, Ayalew;Guglielmelli, Paola;Vannucchi, Alessandro M.
Janus激酶2（JAK 2）突变定义真性红细胞增多症（PV）。钙网蛋白（CALR）和骨髓增生性白血病病毒癌基因（MPL）突变对JAK 2未突变的原发性血小板增多症（ET）和原发性骨髓纤维化（PMF）具有特异性。我们研究了这些突变对长期疾病结局的影响。对来自马约诊所（n = 826）和意大利（n = 755）的1581例患者进行了研究。58%的马约患者随访至死亡; ET组中位生存期为19.8年（n = 292），PV组为13.5年（n = 267;风险比[HR]，1.8; 95%置信区间[CI]，1.4-2.2），PMF组为5.9年（n = 267; HR，4.5; 95% CI，3.5-5.7）。ET相对于PV的生存优势不受JAK 2/CALR/MPL突变状态的影响。ET患者的生存率低于年龄和性别匹配的美国人群（P <0.001）。在PMF（n = 428）中，而不是在ET（n = 576）中，生存和原始细胞转化（BT）受到突变状态的显著影响;结果在CALR突变患者中最好，在三阴性患者中最差：中位生存期，16年vs 2.3年（HR，5.1; 95% CI，3.2-8.0）和BT，分别为6.5%和25%（HR，7.6; 95% CI，2.8-20.2）。我们的结论是，预期寿命在形态学定义的ET显着减少，但仍然上级的PV，无论突变状态。在PMF中，JAK 2/CALR/MPL突变状态具有统计学意义。
Janus kinase 2 (JAK2) mutations define polycythemia vera (PV). Calreticulin (CALR) and myeloproliferative leukemia virus oncogene (MPL) mutations are specific to JAK2-unmutated essential thrombocythemia (ET) and primarymyelofibrosis (PMF). We examined the effect of these mutations on long-term disease outcome. One thousand five hundred eighty-one patients from the Mayo Clinic (n = 826) and Italy (n = 755) were studied. Fifty-eight percent of Mayo patients were followed until death; median survivals were 19.8 years in ET (n = 292), 13.5 PV (n = 267; hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.4-2.2), and 5.9 PMF(n = 267; HR, 4.5; 95% CI, 3.5-5.7). The survival advantage of ET over PV was not affected by JAK2/CALR/MPL mutational status. Survival in ET was inferior to the age-and sex-matched US population (P < .001). In PMF (n = 428), but not in ET (n = 576), survival and blast transformation (BT) were significantly affected by mutational status; outcome was best in CALR-mutated and worst in triple-negative patients: median survival, 16 vs 2.3 years (HR, 5.1; 95% CI, 3.2-8.0) and BT, 6.5% vs 25% (HR, 7.6; 95% CI, 2.8-20.2), respectively. We conclude that life expectancy in morphologically defined ET is significantly reduced but remains superior to that of PV, regardless of mutational status. In PMF, JAK2/CALR/MPL mutational status is prognostically informative.