Registre des Neutropénies Chroniques, Centre de Référence des Neutropénies Chroniques, Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine, Hôpital Trousseau, APHP, Paris, F-75012, France.
IRCCS Giannina Gaslini and Università degli Studi di Genova, Genoa, Italy.
Bone Marrow Transplant. 2020 Aug;55(8):1614-1622. doi: 10.1038/s41409-020-0800-1. Epub 2020 Jan 28.
ELANE neutropenia is associated with myelodysplasia and acute leukemia (MDS-AL), and severe infections. Because the MDS-AL risk has also been shown to be associated with exposure to GCSF, since 2005, in France, patients receiving high daily GCSF doses (>15 μg/kg/day) are eligible for HSCT, in addition to classic indications (MDS-AL or GCSF refractoriness). We analyzed the effect of this policy. Among 144 prospectively followed ELANE-neutropenia patients enrolled in the French Severe Congenital Neutropenia Registry, we defined two groups according to period: "before 2005" for those born before 2005 and followed until 31/12/2004 (1588 person-years); and "after 2005" comprised of those born after 2005 or born before 2005 but followed after 2005 until 31/03/2019 (1327 person-years). Sixteen of our cohort patients underwent HSCT (14 long-term survivors) and six developed MDS-ALs. Six leukemic transformations occurred in the before-2005 group and none after 2005 (respective frequencies 3.8 × 10 vs. 0; P < 0.01), while four HSCTs were done before 2005 and 12 since 2005 (respective HSCT rates increased 2.5 × 10 vs. 9 × 10; P < 0.01). Our results support early HSCT for patients with ELANE mutations who received high GCSF doses, as it might lower the risk of leukemic transformation.
ELANE 中性粒细胞减少症与骨髓增生异常综合征和急性白血病 (MDS-AL) 以及严重感染有关。由于 MDS-AL 风险也与 GCSF 暴露有关，自 2005 年以来，在法国，接受高剂量每日 GCSF (>15μg/kg/天) 的患者除了经典适应症 (MDS-AL 或 GCSF 耐药性) 外，还符合 HSCT 的条件。我们分析了这项政策的效果。在法国严重先天性中性粒细胞减少症登记处前瞻性随访的 144 名 ELANE 中性粒细胞减少症患者中，我们根据时期将其分为两组：“2005 年之前”组，出生于 2005 年之前并随访至 2004 年 12 月 31 日 (1588 人年)；“2005 年之后”组，包括出生于 2005 年之后或出生于 2005 年之前但在 2005 年之后随访至 2019 年 3 月 31 日 (1327 人年)。我们的队列中有 16 名患者接受了 HSCT(14 名长期幸存者)，6 名患者发生了 MDS-AL。2005 年之前组有 6 例白血病转化，而 2005 年之后组没有发生白血病转化(各自的发生率分别为 3.8×10 和 0；P<0.01)，2005 年之前进行了 4 次 HSCT，2005 年之后进行了 12 次 HSCT(各自的 HSCT 率分别增加了 2.5×10 和 9×10；P<0.01)。我们的结果支持对接受高剂量 GCSF 的 ELANE 突变患者进行早期 HSCT，因为这可能降低白血病转化的风险。
