Milá M, Rufach A, Dapena J L, Arostegui J I, Elorza I, Llort A, Sánchez de Toledo J, Díaz de Heredia C
Servicio de Oncología y Hematología Pediátricas, Hospital Materno-Infantil Vall d'Hebron, Barcelona, España.
An Pediatr (Barc). 2011 Dec;75(6):396-400. doi: 10.1016/j.anpedi.2011.05.017. Epub 2011 Jul 14.
Severe congenital neutropenia (SCN), a heterogeneous condition with onset at early ages, is characterised by primary myelopoiesis failure with an absolute neutrophil count (ANC) < 0.5 x10(9)/L, severe infections and risk of leukaemic transformation.
The aim of the study was to ascertain the long term outcome of patients with SCN.
The clinical features, diagnostic methods, treatment and outcome of 11 patients with SCN were analysed.
The median age at diagnosis was 4 months (range: 3 days-12 years). The primary clinical manifestation was severe infection. Median ANC at diagnosis: 0.2 x 10(9)/L (range: 0-0.37). Bone marrow aspirate showed maturation arrest at promyelocyte stage in all cases. Genetic studies revealed 3 mutations, two in ELA-2 gene and 1 in G6PC3 gene, showing a correlation between genotype and phenotype. Granulocyte Colony Stimulating Factor (G-CSF) was the first-line treatment in 9 patients; six of whom showed a good response at doses between 5 and 15 μg/kg/day for 3-7 days/week. The remaining 3 patients failed to respond to G-CSF and allogeneic stem cell transplantation (SCT) was indicated. Furthermore, SCT was the treatment of choice in two cases. Median follow-up of the cohort was 5 years (range: 1-10 years) with 100% survival and no cases of leukaemic transformation.
We conclude that genetic study is useful for establishing a correlation between genotype and phenotype. The treatment of choice for SCN is G-CSF to which 2/3 of patients should respond; while SCT is reserved for cases of poor response or those evolving to myelodysplastic syndrome (MDS) or leukaemia; thus close follow-up of this condition is essential.
严重先天性中性粒细胞减少症（SCN）是一种发病于幼年的异质性疾病，其特征为原发性骨髓造血功能衰竭，绝对中性粒细胞计数（ANC）<0.5×10⁹/L，严重感染以及白血病转化风险。
本研究旨在确定SCN患者的长期预后。
分析11例SCN患者的临床特征、诊断方法、治疗及预后。
诊断时的中位年龄为4个月（范围：3天至12岁）。主要临床表现为严重感染。诊断时的中位ANC：0.2×10⁹/L（范围：0至0.37）。所有病例骨髓穿刺显示早幼粒细胞阶段成熟停滞。基因研究发现3种突变，2种在ELA - 2基因，1种在G6PC3基因，显示出基因型与表型之间的相关性。粒细胞集落刺激因子（G - CSF）是9例患者的一线治疗药物；其中6例患者在剂量为5至15μg/kg/天、每周3至7天的情况下显示出良好反应。其余3例患者对G - CSF无反应，遂行异基因干细胞移植（SCT）。此外，2例患者选择SCT作为治疗方法。该队列的中位随访时间为5年（范围：1至10年），生存率为100%，无白血病转化病例。
我们得出结论，基因研究有助于建立基因型与表型之间的相关性。SCN的首选治疗方法是G - CSF，2/3的患者应会对此有反应；而SCT则用于反应不佳或发展为骨髓增生异常综合征（MDS）或白血病的病例；因此，对这种疾病进行密切随访至关重要。
