Bhoopalan Senthil Velan, Wlodarski Marcin, Reiss Ulrike, Triplett Brandon, Sharma Akshay
Department of Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee.
Pediatr Blood Cancer. 2021 Oct;68(10):e29177. doi: 10.1002/pbc.29177. Epub 2021 Jun 4.
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.
We performed a retrospective analysis on pediatric patients with DKC who underwent HCT at our institution between 2008 and 2019.
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.
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.
先天性角化不良（DKC）中的骨髓衰竭呈进行性发展，异基因造血细胞移植（HCT）是唯一的治愈性治疗方法。然而，由于黏膜、血管、肺部和肝脏的脆弱性，HCT后的结果并不理想，化疗预处理和移植物抗宿主病（GVHD）会加剧这些脆弱性。这些毒性可以通过降低预处理方案的强度来减轻。
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。
我们确定了9例患者（中位年龄5.7岁），他们接受了基于氟达拉滨的减低强度预处理（RIC）方案的HCT。GVHD预防措施包括他克莫司加霉酚酸酯（MMF）（n = 8）、他克莫司/喷司他丁（n = 1）或环孢素/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）。通过肺活量测定法测量的6例患者的肺功能在HCT后的观察期间保持稳定。6例患者（67%）存活，中位随访时间为73.5个月。
由于清髓性预处理后的毒性，RIC正成为DKC中HCT的标准方法。这些结果表明，RIC方案对DKC患者是可行且安全的，并且在HCT后的中短期内不会加速肺部损伤。
