Donadieu Jean, Fenneteau Odile, Beaupain Blandine, Beaufils Sandrine, Bellanger Florence, Mahlaoui Nizar, Lambilliotte Anne, Aladjidi Nathalie, Bertrand Yves, Mialou Valérie, Perot Christine, Michel Gérard, Fouyssac Fanny, Paillard Catherine, Gandemer Virginie, Boutard Patrick, Schmitz Jacques, Morali Alain, Leblanc Thierry, Bellanné-Chantelot Christine
AP-HP Registre Français des Neutropénies Congénitales, Hôpital Trousseau, Service d’Hémato-oncologie Pédiatrique, APHP, Paris, France.
Haematologica. 2012 Sep;97(9):1312-9. doi: 10.3324/haematol.2011.057489. Epub 2012 Apr 4.
Patients with the Shwachman-Diamond syndrome often develop hematologic complications. No risk factors for these complications have so far been identified. The aim of this study was to classify the hematologic complications occurring in patients with Shwachman-Diamond syndrome and to investigate the risk factors for these complications.
One hundred and two patients with Shwachman-Diamond syndrome, with a median follow-up of 11.6 years, were studied. Major hematologic complications were considered in the case of definitive severe cytopenia (i.e. anemia <7 g/dL or thrombocytopenia <20 × 10(9)/L), classified as malignant (myelodysplasia/leukemia) according to the 2008 World Health Organization classification or as non-malignant.
Severe cytopenia was observed in 21 patients and classified as malignant severe cytopenia (n=9), non-malignant severe cytopenia (n=9) and malignant severe cytopenia preceded by non-malignant severe cytopenia (n=3). The 20-year cumulative risk of severe cytopenia was 24.3% (95% confidence interval: 15.3%-38.5%). Young age at first symptoms (<3 months) and low hematologic parameters both at diagnosis of the disease and during the follow-up were associated with severe hematologic complications (P<0.001). Fifteen novel SBDS mutations were identified. Genotype analysis showed no discernible prognostic value. CONCLUSIONS Patients with Shwachman-Diamond syndrome with very early symptoms or cytopenia at diagnosis (even mild anemia or thrombocytopenia) should be considered at a high risk of severe hematologic complications, malignant or non-malignant. Transient severe cytopenia or an indolent cytogenetic clone had no deleterious value.
施瓦赫曼 - 戴蒙德综合征患者常出现血液学并发症。目前尚未确定这些并发症的危险因素。本研究的目的是对施瓦赫曼 - 戴蒙德综合征患者发生的血液学并发症进行分类，并研究这些并发症的危险因素。
对102例施瓦赫曼 - 戴蒙德综合征患者进行研究，中位随访时间为11.6年。确诊为严重血细胞减少（即贫血<7 g/dL或血小板减少<20×10⁹/L）时考虑为主要血液学并发症，根据2008年世界卫生组织分类分为恶性（骨髓增生异常综合征/白血病）或非恶性。
21例患者出现严重血细胞减少，分类为恶性严重血细胞减少（n = 9）、非恶性严重血细胞减少（n = 9）以及非恶性严重血细胞减少先于恶性严重血细胞减少（n = 3）。严重血细胞减少的20年累积风险为24.3%（95%置信区间：15.3% - 38.5%）。首发症状时年龄较小（<3个月）以及疾病诊断时和随访期间血液学参数较低与严重血液学并发症相关（P<0.001）。鉴定出15种新的SBDS突变。基因型分析未显示出明显的预后价值。结论：施瓦赫曼 - 戴蒙德综合征患者如果症状出现非常早或诊断时存在血细胞减少（即使是轻度贫血或血小板减少），应被视为发生严重血液学并发症（恶性或非恶性）的高危人群。短暂的严重血细胞减少或惰性细胞遗传学克隆无不良影响。
