Pediatric Immunohematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy.
Biol Blood Marrow Transplant. 2010 May;16(5):622-8. doi: 10.1016/j.bbmt.2009.11.024. Epub 2009 Dec 4.
beta-thalassemia is a major health problem worldwide, and stem cell transplantation (SCT) is the only curative option. Oral Busulfan (Bu) based conditioning is widely used in this setting. Due to the variability of Bu systemic exposure, intravenous (i.v.) Bu has been proposed as a standard of care, with no need for drug monitoring and dose adjustment. Patients with beta-thalassemia from countries with limited resources might be at higher risk of erratic Bu metabolism because of liver dysfunction, severe iron overload, and specific ethnic/genetic features. We studied Bu pharmacokinetics in 53 children with advanced beta-thalassemia from Middle Eastern countries who underwent a total of 57 matched related donor SCTs. Forty-two percent of the children required dose adjustment because they did not achieve the therapeutic window after the first dose. With a Bu dose-adjustment policy, regimen-related toxicity was limited. At a median follow-up of 564 days, the probabilities of 2-year survival, current thalassemia-free survival, rejection, and treatment-related mortality were 96%, 88%, 21%, and 4%, respectively. Conditioning with i.v. Bu and dose adjustment is feasible and well tolerated, although recurrence of thalassemia remains an unsolved problem in children with advanced disease.
β-地中海贫血是全球范围内的一个重大健康问题，而干细胞移植（SCT）是唯一的治愈方法。在这种情况下，口服白消安（Bu）为基础的预处理方案被广泛应用。由于 Bu 全身暴露的可变性，静脉注射（i.v.）Bu 已被提议作为一种标准治疗方法，无需进行药物监测和剂量调整。来自资源有限国家的β-地中海贫血患者由于肝功能障碍、严重的铁过载和特定的种族/遗传特征，可能存在 Bu 代谢不稳定的更高风险。我们研究了来自中东国家的 53 名患有晚期β-地中海贫血的儿童的 Bu 药代动力学，这些儿童共进行了 57 次匹配的相关供体 SCT。由于第一次剂量后未达到治疗窗，42%的儿童需要调整剂量。通过 Bu 剂量调整方案，方案相关毒性是有限的。在中位数为 564 天的随访中，2 年生存率、当前无地中海贫血生存率、排斥反应和治疗相关死亡率的概率分别为 96%、88%、21%和 4%。虽然对于晚期疾病的儿童来说，地中海贫血的复发仍然是一个未解决的问题，但静脉注射 Bu 联合剂量调整的预处理是可行且耐受良好的。
