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Abstract：
BACKGROUND: Bone marrow failure in dyskeratosis congenita (DKC) is progressive, and allogeneic hematopoietic cell transplantation (HCT) is the only curative treatment. However, outcomes after HCT are suboptimal because of mucosal, vascular, pulmonary, and hepatic fragility, which can be exacerbated by chemotherapy conditioning and graft-versus-host disease (GVHD). These toxicities can be mitigated by reducing the intensity of the conditioning regimen.
METHODS: We performed a retrospective analysis on pediatric patients with DKC who underwent HCT at our institution between 2008 and 2019.
RESULTS: We identified nine patients (median age, 5.7 years) who underwent HCT with a fludarabine-based reduced-intensity conditioning (RIC) regimen. GVHD prophylaxis consisted of tacrolimus plus mycophenolate mofetil (MMF) (n = 8), tacrolimus/pentostatin (n = 1), or cyclosporine/MMF (n = 1). The median time to neutrophil engraftment was 19 days (range, 13-26 days), and the median time to platelet engraftment was 18 days (range, 17-43 days). Lung function, as measured by spirometry in six patients, remained stable during post-HCT observation. Six patients (67%) remain alive, with a median follow-up of 73.5 months.
CONCLUSIONS: Because of toxicity after myeloablative conditioning, RIC is becoming standard for HCT in DKC. These results suggest that RIC regimen is feasible and safe for patients with DKC and does not accelerate pulmonary damage in the short-to-medium term after HCT.
METHODS: We performed a retrospective analysis on pediatric patients with DKC who underwent HCT at our institution between 2008 and 2019.
RESULTS: We identified nine patients (median age, 5.7 years) who underwent HCT with a fludarabine-based reduced-intensity conditioning (RIC) regimen. GVHD prophylaxis consisted of tacrolimus plus mycophenolate mofetil (MMF) (n = 8), tacrolimus/pentostatin (n = 1), or cyclosporine/MMF (n = 1). The median time to neutrophil engraftment was 19 days (range, 13-26 days), and the median time to platelet engraftment was 18 days (range, 17-43 days). Lung function, as measured by spirometry in six patients, remained stable during post-HCT observation. Six patients (67%) remain alive, with a median follow-up of 73.5 months.
CONCLUSIONS: Because of toxicity after myeloablative conditioning, RIC is becoming standard for HCT in DKC. These results suggest that RIC regimen is feasible and safe for patients with DKC and does not accelerate pulmonary damage in the short-to-medium term after HCT.
摘要：
背景：先天性角化不良（DKC）的骨髓衰竭是进行性的，异基因造血细胞移植（HCT）是唯一的治疗方法。然而,由于粘膜，HCT后的结局欠佳，血管,肺,肝脏脆弱,化疗和移植物抗宿主病（GVHD）可能会加剧这种情况。这些毒性可以通过降低调理方案的强度来减轻。
方法：我们对2008年至2019年在我们机构接受HCT的DKC儿科患者进行了回顾性分析。
结果：我们确定了9名患者（中位年龄，5.7年）接受了基于氟达拉滨的降低强度预处理（RIC）方案的HCT。GVHD预防包括他克莫司加霉酚酸酯（MMF）（n=8），他克莫司/喷他汀（n=1），或环孢菌素/MMF（n=1）。中性粒细胞植入的中位时间为19天（范围，13-26天），血小板植入的中位时间为18天(范围，17-43天）。肺功能,通过肺活量测定法对六名患者进行测量，在HCT后观察期间保持稳定。6名患者（67%）仍然存活，中位随访时间为73.5个月。
结论：由于清髓性预处理后的毒性，RIC正在成为DKC中HCT的标准。这些结果表明，RIC方案对于DKC患者是可行且安全的，并且在HCT后的中短期不会加速肺损伤。
方法：我们对2008年至2019年在我们机构接受HCT的DKC儿科患者进行了回顾性分析。
结果：我们确定了9名患者（中位年龄，5.7年）接受了基于氟达拉滨的降低强度预处理（RIC）方案的HCT。GVHD预防包括他克莫司加霉酚酸酯（MMF）（n=8），他克莫司/喷他汀（n=1），或环孢菌素/MMF（n=1）。中性粒细胞植入的中位时间为19天（范围，13-26天），血小板植入的中位时间为18天(范围，17-43天）。肺功能,通过肺活量测定法对六名患者进行测量，在HCT后观察期间保持稳定。6名患者（67%）仍然存活，中位随访时间为73.5个月。
结论：由于清髓性预处理后的毒性，RIC正在成为DKC中HCT的标准。这些结果表明，RIC方案对于DKC患者是可行且安全的，并且在HCT后的中短期不会加速肺损伤。
