Department of Pediatrics, Weill Cornell Medical College, New York, New York.
Pediatr Blood Cancer. 2014 Jul;61(7):1289-94. doi: 10.1002/pbc.24976. Epub 2014 Feb 12.
Cyclophosphamide-based conditioning regimens and allogeneic hematopoietic stem cell transplantation (AlloHSCT) from matched related donors (MRD) has resulted in the highest survival rates in children and adolescents with acquired severe aplastic anemia (SAA). Time to transplant has consistently been associated with decreased overall survival. Reduced toxicity conditioning and AlloHSCT has been used successfully in other pediatric non-malignant diseases.
We piloted a risk-adapted AlloHSCT approach, using fludarabine and anti-thymocyte globulin based conditioning with high (200 mg/kg) and low (60 mg/kg) dose cyclophosphamide as upfront treatment in newly diagnosed pediatric patients with acquired SAA incorporating alternative donor sources, including cord blood. Average risk for non-engraftment patients with <10 transfusions received low dose cyclophosphamide (60 mg/kg); High Risk, those with ≥10 transfusions received conditioning regimen with higher intensity cyclophosphamide (200 mg/kg).
Seventeen patients were enrolled and underwent AlloHSCT including 12 males and 5 females with mean age of 8 years (range 3-16), and median follow-up time of 39 months (range 1-135). Donor sources included MRD BM (6/6 [n = 9], 5/6 [n = 2]) and unrelated CB (5/6 [n = 4], 4/6 [n = 2]). Five year OS was 67.6% (37.9-85.4). Three secondary graft failures (17.6%) occurred in the low dose cyclophosphamide arm.
Upfront treatment with risk-adapted cyclophosphamide conditioning AlloSCT is well tolerated for the management of newly diagnosed pediatric and adolescent patients with acquired SAA. However, the increased risk of graft rejection in the lower dose arm warrants additional research regarding the optimal intensity of cyclophosphamide-based conditioning regimen to reduce toxicity without increasing graft failure.
环磷酰胺为基础的预处理方案和异基因造血干细胞移植（AlloHSCT）来自匹配的亲缘供者（MRD）已导致儿童和青少年获得性严重再生障碍性贫血（SAA）的最高生存率。移植时间一直与总生存率降低有关。在其他儿科非恶性疾病中，已成功使用减少毒性预处理和 AlloHSCT。
我们采用风险适应的 AlloHSCT 方法，在新诊断的儿童获得性 SAA 患者中使用氟达拉滨和抗胸腺细胞球蛋白为基础的预处理，并用高（200mg/kg）和低（60mg/kg）剂量环磷酰胺作为一线治疗，包括替代供者来源，如脐带血。对于非植入患者，平均风险<10 次输血者接受低剂量环磷酰胺（60mg/kg）；高风险者，接受高强度环磷酰胺（200mg/kg）预处理方案。
17 例患者接受了 AlloHSCT，包括 12 例男性和 5 例女性，平均年龄为 8 岁（范围 3-16），中位随访时间为 39 个月（范围 1-135）。供者来源包括 MRD BM（6/6 [n=9]，5/6 [n=2]）和无关 CB（5/6 [n=4]，4/6 [n=2]）。5 年 OS 为 67.6%（37.9-85.4）。在低剂量环磷酰胺组中发生了 3 例继发性移植物失败（17.6%）。
在新诊断的儿童和青少年获得性 SAA 患者中，采用风险适应的环磷酰胺预处理 AlloSCT 作为一线治疗是可以耐受的。然而，低剂量组中移植物排斥的风险增加需要进一步研究以确定最佳强度的环磷酰胺为基础的预处理方案，以降低毒性而不增加移植物失败的风险。
