Aflac Cancer Center and Blood Disorders Service, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.
Bone Marrow Transplant. 2011 Jan;46(1):27-33. doi: 10.1038/bmt.2010.60. Epub 2010 Mar 22.
Busulfan influences engraftment and toxicities during hematopoietic stem cell transplantation (HSCT). We report our single-institution experience of targeted busulfan therapy for myeloablative, matched sibling donor (MSD) HSCT for sickle cell disease (SCD) and assess the relationships of busulfan levels to engraftment and toxicities. Twenty-seven patients with SCD underwent MSD HSCT from 1993 to 2007, 25 with busulfan measurements. The conditioning regimen was busulfan (initial dose 0.875 mg/kg for 16 doses), CY and antithymocyte globulin. Busulfan area under curve (AUC) was determined with the first dose, and dose adjustments were made to target the desired AUC range. Median AUC was 963 μmol min/L (range 780-1305 μmol min/L). Engraftment occurred in all cases: 21 (84%) full donor chimerism (> 95% donor cells), 4 (16%) partial donor chimerism. Hepatic veno-occlusive disease (VOD) occurred in 8 (32%) patients. Lower AUC was seen with partial donor chimerism (862 ± 73 μmol min/L) versus full donor chimerism (AUC 1018 ± 122 μmol min/L) (P = 0.022). VOD was not associated with busulfan AUC (P = 0.153). Of 25 patients, 24 survived with median follow-up of 4.9 years. Our experience shows that targeting busulfan AUC above the range used in previous multicenter trials appears safe and may contribute to sustained engraftment in SCD.
白消安会影响造血干细胞移植（HSCT）中的植入和毒性。我们报告了我们在单中心进行的针对骨髓清除性、匹配的同胞供体（MSD）HSCT 治疗镰状细胞病（SCD）的靶向白消安治疗经验，并评估了白消安水平与植入和毒性的关系。1993 年至 2007 年，27 例 SCD 患者接受了 MSD HSCT，其中 25 例进行了白消安测量。预处理方案为白消安（初始剂量 0.875mg/kg，共 16 剂）、环磷酰胺和抗胸腺细胞球蛋白。通过第一剂确定白消安的 AUC，并进行剂量调整以达到所需的 AUC 范围。中位数 AUC 为 963μmol min/L（范围 780-1305μmol min/L）。所有病例均发生植入：21 例（84%）完全供者嵌合体（>95%供体细胞），4 例（16%）部分供者嵌合体。8 例（32%）患者发生肝静脉闭塞性疾病（VOD）。部分供者嵌合体（862±73μmol min/L）的 AUC 低于完全供者嵌合体（AUC 1018±122μmol min/L）（P=0.022）。VOD 与白消安 AUC 无关（P=0.153）。25 例患者中，24 例存活，中位随访时间为 4.9 年。我们的经验表明，靶向白消安 AUC 高于先前多中心试验使用的范围似乎是安全的，并可能有助于 SCD 的持续植入。
