Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
Pediatr Blood Cancer. 2011 Mar;56(3):444-51. doi: 10.1002/pbc.22836.
Severe congenital neutropenia (SCN) is an immunodeficiency characterized by disturbed myelopoiesis and an absolute neutrophil count (ANC) <0.5 × 10(9)/L. SCN is also a premalignant condition; a significant proportion of patients develop myelodysplastic syndrome or leukemia (MDS/L). Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for SCN.
Since 2004, eight HSCT have been performed in seven patients at our center. The indications were transformation to MDS/L (n = 2), granulocyte colony-stimulating factor receptor (CSF3R) mutation(s) (n = 2), granulocyte colony-stimulating factor (G-CSF) resistance (n = 2), and at the patient's own request (n = 1).
The mean age at transplantation was 13 years (2.8-28 years) (mean follow-up 32 months, range 21-60). Three patients harbored ELANE mutations, three HAX1 mutations, and in one patient no causative mutation was identified. Two of the ELANE mutations were novel mutations. Three patients initially received myeloablative conditioning and four had reduced intensity conditioning (RIC). Three grafts were from HLA-identical siblings, three from matched unrelated donors and two were cord blood units. Engraftment occurred in all patients. Two of seven (29%) patients died; both had MDS/L and both were among the three that underwent myeloablative conditioning. One patient has chronic GVHD 2 years post-transplant.
The role of HSCT should be explored further in patients with SCN. In particular, the influence of the conditioning regime needs to be evaluated in a larger cohort of patients.
严重先天性中性粒细胞减少症（SCN）是一种免疫缺陷，其特征为骨髓生成紊乱和绝对中性粒细胞计数（ANC）<0.5×10(9)/L。SCN 也是一种癌前状态；相当一部分患者会发展为骨髓增生异常综合征或白血病（MDS/L）。异基因造血干细胞移植（HSCT）是 SCN 的唯一治愈性治疗方法。
自 2004 年以来，我们中心对 7 名患者进行了 8 次 HSCT。适应证为转化为 MDS/L（n=2）、粒细胞集落刺激因子受体（CSF3R）突变（n=2）、粒细胞集落刺激因子（G-CSF）耐药（n=2）和患者自身要求（n=1）。
移植时的平均年龄为 13 岁（2.8-28 岁）（平均随访 32 个月，范围 21-60）。3 名患者携带 ELANE 突变，3 名携带 HAX1 突变，1 名患者未发现致病突变。2 个 ELANE 突变是新的突变。3 名患者最初接受了清髓性预处理，4 名患者接受了强度降低的预处理（RIC）。3 个移植物来自 HLA 匹配的同胞，3 个来自匹配的无关供体，2 个来自脐带血单位。所有患者均发生移植物植入。7 名患者中的 2 名（29%）死亡；均患有 MDS/L，且均为接受清髓性预处理的 3 名患者之一。1 名患者在移植后 2 年患有慢性移植物抗宿主病。
应进一步探讨 HSCT 在 SCN 患者中的作用。特别是，需要在更大的患者队列中评估预处理方案的影响。
