Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology 'L. and A. Seràgnoli', University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy.
Leukemia. 2015 Jun;29(6):1344-9. doi: 10.1038/leu.2015.87. Epub 2015 Mar 24.
We investigated the influence of molecular status on disease characteristics and clinical outcome in young patients (⩽ 40 years) with World Health Organization (WHO)-defined essential thrombocythemia (ET) or early/prefibrotic primary myelofibrosis (early-PMF). Overall, 217 patients with ET (number 197) and early-PMF (number 20) were included in the analysis. Median follow-up time was 10.2 years. The cumulative incidence of thrombosis, hemorrhages and disease evolution into myelofibrosis/acute leukemia were 16.6%, 8.6% and 3% at 15 years, respectively. No differences were detectable between ET and early-PMF patients, although the latter cohort showed a trend for worse combined-event free survival (EFS). Mutation frequency were 61% for JAK2V617F, 25% for CALR and 1% for MPLW515K, and were comparable across WHO diagnosis; however, JAK2V617F allele burden was higher in the early-PMF group. Compared with JAK2V617F-positive patients, CALR-mutated patients displayed higher platelet count and lower hemoglobin level. CALR mutations significantly correlated with lower thrombotic risk (9.1% versus 21.7%, P = 0.04), longer survival (100% versus 96%, P = 0.05) and better combined-EFS (86% versus 71%, P = 0.02). However, non-type 1/type 2 CALR mutations ('minor' mutations) and abnormal karyotype were found to correlate with increased risk of disease evolution. At last contact, six patients had died; in five cases, the causes of death were related to the hematological disease and occurred at a median age of 64 years (range: 53-68 years). Twenty-eight patients (13%) were unmutated for JAK2, CALR and MPL: no event was registered in these 'triple-negative' patients.
我们研究了分子状态对年轻患者（年龄 ⩽ 40 岁）中世界卫生组织（WHO）定义的原发性血小板增多症（ET）或早期/纤维化前期原发性骨髓纤维化（早期-PMF）的疾病特征和临床结局的影响。总体而言，纳入了 217 例 ET（197 例）和早期-PMF（20 例）患者进行分析。中位随访时间为 10.2 年。15 年时血栓形成、出血和疾病演变为骨髓纤维化/急性白血病的累积发生率分别为 16.6%、8.6%和 3%。尽管后者队列的联合无事件生存（EFS）呈下降趋势，但在 ET 和早期-PMF 患者之间未检测到差异。JAK2V617F 的突变频率为 61%，CALR 为 25%，MPLW515K 为 1%，在 WHO 诊断中无差异；然而，早期-PMF 组 JAK2V617F 等位基因负荷更高。与 JAK2V617F 阳性患者相比，CALR 突变患者的血小板计数更高，血红蛋白水平更低。CALR 突变与较低的血栓形成风险显著相关（9.1%比 21.7%，P = 0.04）、更长的生存时间（100%比 96%，P = 0.05）和更好的联合 EFS（86%比 71%，P = 0.02）。然而，非 1/2 型 CALR 突变（“次要”突变）和异常核型与疾病进展风险增加相关。最后一次随访时，有 6 例患者死亡；在 5 例中，死亡原因与血液疾病有关，中位年龄为 64 岁（范围：53-68 岁）。28 例（13%）患者 JAK2、CALR 和 MPL 均未突变：这些“三阴性”患者未发生任何事件。
