Department of Hematology and Bone marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milano, Italy; Cellular Therapy and Immunobiology Working Party, Leiden, The Netherlands.
EBMT Paediatric Diseases Working Party, Paris, France.
Transplant Cell Ther. 2021 May;27(5):424.e1-424.e9. doi: 10.1016/j.jtct.2021.01.016. Epub 2021 Jan 21.
HLA-haploidentical transplantation (haplo-HCT) using post-transplantation-cyclophosphamide (PT-Cy) is a feasible procedure in children with malignancies. However, large studies on Haplo-HCT with PT-Cy for childhood acute lymphoblastic leukemia (ALL) are lacking. We analyzed haplo-HCT outcomes in 180 children with ALL. Median age was 9 years, and median follow-up was 2.7 years. Disease status was CR1 for 24%, CR2 for 45%, CR+3 for 12%, and active disease for 19%. All patients received PT-Cy day +3 and +4. Bone marrow (BM) was the stem cell source in 115 patients (64%). Cumulative incidence of 42-day engraftment was 88.9%. Cumulative incidence of day-100 acute graft-versus-host disease (GVHD) grade II-IV was 28%, and 2-year chronic GVHD was 21.9%. At 2 years, cumulative incidence of nonrelapse mortality (NRM) was 19.6%. Cumulative incidence was 41.9% for relapse and 25% for patients in CR1. Estimated 2-year leukemia free survival was 65%, 44%, and 18.8% for patients transplanted in CR1, CR2, CR3+ and 3% at 1 year for active disease. In multivariable analysis for patients in CR1 and CR2, disease status (CR2 [hazard ratio {HR} = 2.19; P = .04]), age at HCT older than 13 (HR = 2.07; P = .03) and use of peripheral blood stem cell (PBSC) (HR = 1.98; P = .04) were independent factors associated with decreased overall survival. Use of PBSC was also associated with higher NRM (HR = 3.13; P = .04). Haplo-HCT with PT-Cy is an option for children with ALL, namely those transplanted in CR1 and CR2. Age and disease status remain the most important factors for outcomes. BM cells as a graft source is associated with improved survival.
HLA 单倍体移植（haplo-HCT）联合移植后环磷酰胺（PT-Cy）在恶性肿瘤儿童中是一种可行的方法。然而，缺乏儿童急性淋巴细胞白血病（ALL）采用haplo-HCT 联合 PT-Cy 的大型研究。我们分析了 180 例 ALL 患儿的 haplo-HCT 结果。中位年龄为 9 岁，中位随访时间为 2.7 年。疾病状态为 CR1 期 24%，CR2 期 45%，CR+3 期 12%，活动期 19%。所有患者均于+3 天和+4 天接受 PT-Cy。115 例患者（64%）以骨髓（BM）作为干细胞来源。42 天植入的累积发生率为 88.9%。100 天急性移植物抗宿主病（GVHD）Ⅱ-Ⅳ级的累积发生率为 28%，2 年慢性 GVHD 为 21.9%。2 年时，非复发死亡率（NRM）的累积发生率为 19.6%。CR1 期患者的累积复发率为 41.9%，CR1 期患者为 25%。移植后 CR1、CR2、CR3+和活动期患者的 2 年无白血病生存率分别为 65%、44%和 18.8%，1 年时活动期患者为 3%。在 CR1 和 CR2 患者的多变量分析中，疾病状态（CR2 [风险比 {HR} = 2.19；P =.04]）、HCT 时年龄大于 13 岁（HR = 2.07；P =.03）和外周血干细胞（PBSC）的使用（HR = 1.98；P =.04）是与总生存期降低相关的独立因素。PBSC 的使用也与较高的 NRM 相关（HR = 3.13；P =.04）。haplo-HCT 联合 PT-Cy 是 ALL 患儿的一种选择，特别是移植后处于 CR1 和 CR2 期的患儿。年龄和疾病状态仍然是影响结局的最重要因素。作为移植物来源的 BM 细胞与生存改善相关。
