Alsultan Abdulrahman, Abujoub Rodina, Elbashir Enas, Essa Mohammed F
Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Oncology Center, King Saud University Medical City, Riyadh, Saudi Arabia.
Clin Transplant. 2022 Nov;36(11):e14787. doi: 10.1111/ctr.14787. Epub 2022 Aug 19.
Allogeneic hematopoietic stem cell transplantation (HSCT) provides a cure for patients with sickle cell disease (SCD). This study describes the effect of conditioning regimen intensity on HSCT outcomes among children younger than 14 years with SCD.
Transplants from HLA-matched related donors (MRD) and unrelated donors (MUD) using either myeloablative conditioning (MAC) regimens or reduced intensity conditioning (RIC) regimens were considered. Event-free survival (EFS) was the primary endpoint. Secondary endpoints included overall survival (OS) and occurrence of GVHD.
48 SCD patients underwent HSCT, 45 (93.8%) patients had MRD, 1 (2.1%) had 9/10 related donor, and 2 (4.1%) had MUD. The median age at transplant was 8.6 years (range, 3.1-13.8). Conditioning regimens were myeloablative (MAC) in 41 (85.4%) patients and of reduced intensity in 7 (14.6%) patients. EFS at 2 years was 100% among MAC group compared to 29% in the RIC group (p < .001). The median follow-up was 43.4 months (range 26.8-134). All events in the RIC group were secondary graft failure. However, OS was 100% in both groups at 2 years. Acute GVHD II-IV was diagnosed in 2 (4.1%) patients. Chronic GVHD occurred in 2 (4.1%) patients. GVHD did not occur in patients who underwent MUD HSCT.
MAC in children with SCD is well tolerated and associated with an excellent outcome for HLA-matched HSCT in SCD. There was a high rate of secondary graft failure with the use of RIC. Future studies are needed to optimize RIC regimens in HSCT of children with SCD.
异基因造血干细胞移植（HSCT）为镰状细胞病（SCD）患者提供了治愈的可能。本研究描述了预处理方案强度对14岁以下SCD儿童HSCT预后的影响。
考虑采用清髓性预处理（MAC）方案或减低强度预处理（RIC）方案，从人类白细胞抗原（HLA）匹配的相关供者（MRD）和无关供者（MUD）进行移植。无事件生存期（EFS）是主要终点。次要终点包括总生存期（OS）和移植物抗宿主病（GVHD）的发生情况。
48例SCD患者接受了HSCT，45例（93.8%）患者有MRD，1例（2.1%）有9/10相合的相关供者，2例（4.1%）有MUD。移植时的中位年龄为8.6岁（范围3.1 - 13.8岁）。41例（85.4%）患者采用清髓性预处理（MAC）方案，7例（14.6%）患者采用减低强度预处理方案。MAC组2年时的EFS为100%，而RIC组为29%（p <.001）。中位随访时间为43.4个月（范围26.8 - 134个月）。RIC组的所有事件均为继发性移植物失败。然而，两组2年时的OS均为100%。2例（4.1%）患者诊断为急性GVHD II - IV级。2例（4.1%）患者发生慢性GVHD。接受MUD HSCT的患者未发生GVHD。
SCD儿童采用MAC预处理耐受性良好，且与HLA匹配的HSCT在SCD中的良好预后相关。使用RIC时继发性移植物失败率较高。未来需要开展研究以优化SCD儿童HSCT中的RIC方案。
