Normal karyotype is a poor prognostic factor in myeloid leukemia of Down syndrome: a retrospective, international study
Normal karyotype is a poor prognostic factor in myeloid leukemia of Down syndrome: a retrospective, international study
复制标题
DOI：
10.3324/haematol.2013.089425
复制
发表时间：
2014-02-01
期刊：
影响因子：
10.1
通讯作者：
Zwaan, C. Michel
中科院分区：
文献类型：
--
作者：
Blink, Marjolein;Zimmermann, Martin;Zwaan, C. Michel
唐氏综合征的髓系白血病比散发性儿童急性髓系白血病预后好。大多数唐氏综合征的髓性白血病病例的特征是除了体质性21三体之外还存在其他细胞遗传学改变，但其潜在的预后影响尚不清楚。因此，我们对451例唐氏综合征髓性白血病患儿的临床特征、细胞遗传学、治疗和预后进行了一项国际回顾性研究。在将患者分配至亚组之前，对所有核型进行集中审查。整个队列的总体7年无事件生存率为78%（+/- 2%），总生存率为79%（+/- 2%），累积复发率为12%（+/- 2%），累积毒性死亡率为7%（+/- 1%）。结果估计显示不同细胞遗传学亚组之间存在较大差异。根据复发的累积发生率，我们可以将患者风险分层为两组：核型正常的病例（n=103）的累积复发发生率（21%+/- 4%）高于核型异常的病例（n=255），累积复发发生率为9%（+/- 2%）（P=0.004）。多变量分析显示，白色血细胞计数>= 20 × 10（9）/L和年龄>3岁是无事件生存率差的独立预测因素，而正常核型独立预测总生存率、无事件生存率和无复发生存率差。总之，本研究显示唐氏综合征髓性白血病患者的结局存在很大差异，并确定了预测临床结局的新预后组，因此可用于未来治疗方案的分层。
Myeloid leukemia of Down syndrome has a better prognosis than sporadic pediatric acute myeloid leukemia. Most cases of myeloid leukemia of Down syndrome are characterized by additional cytogenetic changes besides the constitutional trisomy 21, but their potential prognostic impact is not known. We, therefore, conducted an international retrospective study of clinical characteristics, cytogenetics, treatment, and outcome of 451 children with myeloid leukemia of Down syndrome. All karyotypes were centrally reviewed before assigning patients to subgroups. The overall 7-year event-free survival for the entire cohort was 78% (+/- 2%), with the overall survival rate being 79% (+/- 2%), the cumulative incidence of relapse 12% (+/- 2%), and the cumulative incidence of toxic death 7% (+/- 1%). Outcome estimates showed large differences across the different cytogenetic subgroups. Based on the cumulative incidence of relapse, we could risk-stratify patients into two groups: cases with a normal karyotype (n=103) with a higher cumulative incidence of relapse (21%+/- 4%) than cases with an aberrant karyotype (n=255) with a cumulative incidence of relapse of 9% (+/- 2%) (P=0.004). Multivariate analyses revealed that white blood cell count >= 20x10(9)/L and age >3 years were independent predictors for poor event-free survival, while normal karyotype independently predicted inferior overall survival, event-free survival, and relapse-free survival. In conclusion, this study showed large differences in outcome within patients with myeloid leukemia of Down syndrome and identified novel prognostic groups that predicted clinical outcome and hence may be used for stratification in future treatment protocols.