Pediatric Hematology-Immunology and Rheumatology Unit, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; INSERM U1163 and Institut Imagine, Paris, France; Paris-Descartes University, Sorbonne Paris Cité, Paris, France.
Pediatric Hematology-Immunology and Rheumatology Unit, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; Paris-Descartes University, Sorbonne Paris Cité, Paris, France; Biotherapy Department, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
Biol Blood Marrow Transplant. 2019 Jul;25(7):1363-1373. doi: 10.1016/j.bbmt.2019.03.009. Epub 2019 Mar 12.
Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for some inherited disorders, including selected primary immunodeficiencies (PIDs). In the absence of a well-matched donor, HSCT from a haploidentical family donor (HIFD) may be considered. In adult recipients high-dose post-transplant cyclophosphamide (PTCY) is increasingly used to mitigate the risks of graft failure and graft-versus-host disease (GVHD). However, data on the use of PTCY in children (and especially those with inherited disorders) are scarce. We reviewed the outcomes of 27 children transplanted with an HIFD and PTCY for a PID (n = 22) or osteopetrosis (n = 5) in a single center. The median age was 1.5 years (range, .2 to 17). HSCT with PTCY was a primary procedure (n = 21) or a rescue procedure after graft failure (n = 6). The conditioning regimen was myeloablative in most primary HSCTs and nonmyeloablative in rescue procedures. After a median follow-up of 25.6 months, 24 of 27 patients had engrafted. Twenty-one patients are alive and have been cured of the underlying disease. The 2-year overall survival rate was 77.7%. The cumulative incidences of acute GVHD grade ≥ II, chronic GVHD, and autoimmune disease were 45.8%, 24.2%, and 29.6%, respectively. There were 2 cases of grade III acute GVHD and no extensive cGVHD. The cumulative incidences of blood viral replication and life-threatening viral events were 58% and 15.6%, respectively. There was evidence of early T cell immune reconstitution. In the absence of an HLA-identical donor, HIFD HSCT with PTCY is a viable option for patients with life-threatening inherited disorders.
异基因造血干细胞移植（HSCT）是某些遗传性疾病的潜在治愈方法，包括一些原发性免疫缺陷病（PID）。在没有匹配供体的情况下，可能会考虑来自单倍体家族供体（HIFD）的 HSCT。在成人受者中，越来越多地使用高剂量移植后环磷酰胺（PTCY）来降低移植物失败和移植物抗宿主病（GVHD）的风险。然而，关于 PTCY 在儿童（尤其是遗传性疾病患儿）中的应用的数据很少。我们回顾了在一家中心接受 HIFD 和 PTCY 治疗的 27 例 PID（n=22）或成骨不全症（n=5）患儿的移植结果。中位年龄为 1.5 岁（范围，0.2 至 17 岁）。HSCT 联合 PTCY 是主要治疗手段（n=21）或移植物失败后的挽救治疗（n=6）。预处理方案在大多数原发性 HSCT 中为清髓性，在挽救性治疗中为非清髓性。中位随访 25.6 个月后，27 例患者中有 24 例植入。21 例患者存活且疾病治愈。2 年总生存率为 77.7%。急性 GVHD Ⅱ级及以上、慢性 GVHD 和自身免疫性疾病的累积发生率分别为 45.8%、24.2%和 29.6%。有 2 例 3 级急性 GVHD，无广泛 cGVHD。血液病毒复制和危及生命的病毒事件的累积发生率分别为 58%和 15.6%。有早期 T 细胞免疫重建的证据。在没有 HLA 匹配供体的情况下，HIFD 联合 PTCY 是危及生命的遗传性疾病患者的可行选择。
