Department of Pediatric Blood and Marrow Transplantation, Princess Máxima Center for Pediatric Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
Department of Pediatrics, Stem Cell Transplantation and Cellular Therapy, Memorial Sloan Kettering, New York, NY, USA.
Bone Marrow Transplant. 2021 Jun;56(6):1426-1432. doi: 10.1038/s41409-020-01201-w. Epub 2021 Jan 19.
The impact of conditioning regimen prior to hematopoietic cell transplant (HCT) in pediatric AML-patients is not well studied. We retrospectively analyzed the impact of Busulfan-Cyclophosphamide (BuCy), Busulfan-Cyclophosphamide-Melphalan (BuCyMel) and Clofarabine-Fludarabine-Busulfan (CloFluBu) in pediatric AML-patients, with similar upfront leukemia treatment (NOPHO-DBHconsortium), receiving an HCT between 2010 and 2015. Outcomes of interest were LFS, relapse, TRM and GvHD. 103 patients were included; 30 received BuCy, 37 BuCyMel, and 36 CloFluBu. The 5-years LFS was 43.3% (SE ± 9.0) in the BuCy group, 59.2 % (SE ± 8.1) after BuCyMel, and 66.7 % (SE ± 7.9) after CloFluBu. Multivariable Cox regression analysis showed a trend to lower LFS after BuCy compared to CloFluBu (p = 0.07). BuCy was associated with a higher relapse incidence compared to the other regimens (p = 0.06). Younger age was a predictor for relapse (p = 0.02). A strong correlation between Busulfan Therapeutic Drug Monitoring (TDM) and lower incidence of aGvHD (p < 0.001) was found. In conclusion, LFS after BuCyMel and CloFluBu was comparable, lower LFS was found after BuCy, due to higher relapse incidence. CloFluBu was associated with lower incidence of aGvHD, suggesting lower toxicity with this type of conditioning. This finding is also explained by the impact of Busulfan monitoring.
在儿科急性髓系白血病（AML）患者中，造血细胞移植（HCT）前预处理方案的影响尚未得到充分研究。我们回顾性分析了在接受类似初始白血病治疗（北欧儿科白血病-淋巴瘤研究组[NOPHO]-DBH 协作组）的儿科 AML 患者中，使用白消安-环磷酰胺（BuCy）、白消安-环磷酰胺-美法仑（BuCyMel）和克拉屈滨-氟达拉滨-白消安（CloFluBu）作为预处理方案对 HCT 结果的影响，这些患者均于 2010 年至 2015 年间接受 HCT。感兴趣的结局包括无事件生存（EFS）、复发、治疗相关死亡率（TRM）和移植物抗宿主病（GVHD）。共纳入 103 例患者，其中 30 例接受 BuCy、37 例接受 BuCyMel、36 例接受 CloFluBu。BuCy 组、BuCyMel 组和 CloFluBu 组的 5 年 EFS 分别为 43.3%（标准误±9.0）、59.2%（标准误±8.1）和 66.7%（标准误±7.9）。多变量 Cox 回归分析显示，与 CloFluBu 相比，BuCy 组的 EFS 较低，差异有统计学意义（p=0.07）。与其他方案相比，BuCy 与更高的复发率相关（p=0.06）。年龄较小是复发的预测因素（p=0.02）。发现白消安治疗药物监测（TDM）与 aGVHD 发生率降低之间存在很强的相关性（p<0.001）。总之，BuCyMel 和 CloFluBu 后的 EFS 相似，BuCy 后的 EFS 较低，原因是复发率较高。CloFluBu 与 aGVHD 发生率较低相关，提示这种预处理方案的毒性较低。这一发现也可以用白消安监测的影响来解释。
