Within our nationwide registry, we identified aKITD816V mutation (KITD816Vpos.)in 280/299 (94%) patients with advanced systemic mastocytosis (AdvSM). Age, cytopenias and the presence of additional somatic mutations confer inferior overall survival (OS). However, little is known about the characteristics ofKITD816V-negative (D816Vneg.) AdvSM. In 19 D816Vneg.patients, a combination of clinical, morphological and genetic features revealed three subgroups: (a)KITD816H- or Y-positive SM (KITD816H/Ypos.,n= 7), predominantly presenting as mast cell leukemia (MCL; 6/7 patients), (b) MCL with negativeKITsequencing (KITneg.MCL,n= 7) and (c)KITneg.SM with associated hematologic neoplasm (KITneg.SM-AHN,n= 5). Although >70% of patients in the two MCL cohorts (KITD816H/Ypos.andKITneg.) were classified as low/intermediate risk according to prognostic scoring systems (PSS), treatment response was poor and median OS was shorter than in aKITD816Vpos.MCL control cohort (n= 29; 1.7 vs. 0.9 vs. 2.6 years;p< 0.04). TheKITneg.SM-AHN phenotype was dominated by the heterogeneous AHN (low mast cell burden, presence of additional mutations) with a better median OS of 4.5 years. We conclude that (i) in MCL, negativity for D816V is a relevant prognostic factor and (ii) PSS fail to correctly classify D816Vneg.patients.
在我们全国性的注册研究中，我们在299例晚期系统性肥大细胞增多症（AdvSM）患者中的280例（94%）中检测到KITD816V突变（KITD816V阳性）。年龄、血细胞减少以及存在其他体细胞突变与较差的总生存期（OS）相关。然而，对于KITD816V阴性（D816V阴性）AdvSM的特征知之甚少。在19例D816V阴性患者中，结合临床、形态学和遗传学特征，我们识别出三个亚组：（a）KITD816H或Y阳性SM（KITD816H/Y阳性，n=7），主要表现为肥大细胞白血病（MCL；6/7的患者），（b）KIT测序阴性的MCL（KIT阴性MCL，n=7），以及（c）伴有相关血液肿瘤的KIT阴性SM（KIT阴性SM-AHN，n=5）。尽管在两个MCL队列（KITD816H/Y阳性和KIT阴性）中，超过70%的患者根据预后评分系统（PSS）被归类为低/中危，但治疗反应不佳，中位OS短于KITD816V阳性MCL对照组（n=29；分别为1.7年 vs. 0.9年 vs. 2.6年；p < 0.04）。KIT阴性SM-AHN表型以异质性的AHN（肥大细胞负荷低，存在其他突变）为主，其中位OS较好，为4.5年。我们得出结论：（i）在MCL中，D816V阴性是一个相关的预后因素；（ii）PSS未能正确分类D816V阴性患者。
肿瘤(癌症)患者之家