Pediatric Hemato-Oncology, La Paz University Hospital, idiPAZ Research Institute, Madrid, Spain; Pediatric Hemato-Oncology, La Paz University Hospital, Madrid, Spain.
Pediatric Hemato-Oncology, Hospital Gregorio Marañón, Madrid, Spain.
Transplant Cell Ther. 2023 Nov;29(11):702.e1-702.e11. doi: 10.1016/j.jtct.2023.08.016. Epub 2023 Aug 16.
Increasing data on treosulfan-based conditioning regimens before hematopoietic stem cell transplantation (HSCT) demonstrate the consistent benefits of this approach, particularly regarding acute toxicity. This study aimed to describe the results of treosulfan-based conditioning regimens in children, focusing on toxicity and outcomes when used to treat both malignant and nonmalignant diseases. This retrospective observational study of pediatric patients treated in Spain with treosulfan-based conditioning regimens before HSCT was based on data collection from electronic clinical records. We studied a total of 160 treosulfan-based conditioning HSCTs to treat nonmalignant diseases (n = 117) or malignant diseases (n = 43) in 158 children and adolescents. The median patient age at HSCT was 5.1 years (interquartile range, 2 to 10 years). The most frequent diagnoses were primary immunodeficiency (n = 42; 36%) and sickle cell disease (n = 42; 36%) in the nonmalignant disease cohort and acute lymphoblastic leukemia (n = 15; 35%) in the malignant disease cohort. Engraftment occurred in 97% of the patients. The median times to neutrophil engraftment (17 days versus 14 days; P = .008) and platelet engraftment (20 days versus 15 days; P = .002) were linger in the nonmalignant cohort. The 1-year cumulative incidence of veno-occlusive disease was 7.98% (95% confidence interval [CI], 4.6% to 13.6%), with no significant differences between cohorts. The 1-year cumulative incidence of grade III-IV acute graft-versus-host disease (GVHD) was higher in the malignant disease cohort (18% versus 3.2%; P = .011). Overall, the malignant cohort had both a higher total incidence (9% versus 3%; P < .001) and a higher 2-year cumulative incidence (16% versus 1.9%; P < .001) of total chronic GVHD. The 2-year cumulative transplantation-related mortality was 15%, with no difference between the 2 cohorts. The 5-year overall survival was 80% (95% CI, 72% to 86%) and was higher in the nonmalignant cohort (87% versus 61%; P = .01). The 2-year cumulative incidence of relapse was 25% in the malignant cohort. The 5-year cumulative GVHD-free, relapse-free survival rate was 60% (95% CI, 51% to 70%) and was higher in the nonmalignant cohort (72% versus 22%; P < .001). A treosulfan-based radiation-free conditioning regimen is feasible, achieving a high engraftment rate and 5-year overall survival, and is an emerging option for the first HSCT in nonmalignant diseases.
基于三氟尿苷的预处理方案在造血干细胞移植（HSCT）前的数据不断增加，证明了这种方法的一致益处，特别是在急性毒性方面。本研究旨在描述儿童中基于三氟尿苷的预处理方案的结果，重点是在治疗恶性和非恶性疾病时的毒性和结局。这项对西班牙接受基于三氟尿苷的预处理方案的儿科患者进行的回顾性观察性研究基于电子临床记录中的数据收集。我们研究了 158 名儿童和青少年中 160 例接受基于三氟尿苷的预处理 HSCT 治疗非恶性疾病（n=117）或恶性疾病（n=43）的情况。HSCT 时患者的中位年龄为 5.1 岁（四分位距，2 至 10 岁）。最常见的诊断是非恶性疾病组的原发性免疫缺陷（n=42；36%）和镰状细胞病（n=42；36%），恶性疾病组为急性淋巴细胞白血病（n=15；35%）。97%的患者发生了植入。中性粒细胞植入的中位时间（17 天比 14 天；P=0.008）和血小板植入的中位时间（20 天比 15 天；P=0.002）在非恶性组中更长。静脉阻塞性疾病的 1 年累积发生率为 7.98%（95%置信区间，4.6%至 13.6%），两个队列之间无显著差异。恶性疾病组 1 年累积发生率为 3 级至 4 级急性移植物抗宿主病（GVHD）较高（18%比 3.2%；P=0.011）。总体而言，恶性组的总发生率（9%比 3%；P<0.001）和 2 年累积发生率（16%比 1.9%；P<0.001）均较高。总慢性 GVHD 的 2 年累积移植相关死亡率为 15%，两个队列之间无差异。5 年总生存率为 80%（95%置信区间，72%至 86%），非恶性组更高（87%比 61%；P=0.01）。恶性组的 2 年累积复发率为 25%。恶性疾病组 5 年无 GVHD、无复发生存率为 60%（95%置信区间，51%至 70%），非恶性组更高（72%比 22%；P<0.001）。无放疗的基于三氟尿苷的预处理方案是可行的，可实现高植入率和 5 年总生存率，并且是治疗非恶性疾病的首例 HSCT 的一种新兴选择。
