Ellis R, Boggild M
Walton Centre for Neurology and Neurosurgery, Neurological Sciences, Liverpool, UK.
Mult Scler. 2009 Apr;15(4):505-8. doi: 10.1177/1352458508100967. Epub 2009 Feb 27.
Therapy-related acute leukaemia (TRAL) is a concern for neurologists and patients when considering treatment with Mitoxantrone for multiple sclerosis (MS). The timing of this complication, risk, mortality and relationship to exposure remain uncertain.
We searched literature for publications relating to Mitoxantrone in MS, reviewed publication references and handsearched abstract lists to identify case-series reporting follow-up and complications of treatment with Mitoxantrone. We combined this with our local database of 250 cases treated since 1997. We also identified all reported individual cases of TRAL and extracted data reporting exposure (dose or mg/m(2)), timing and outcome of TRAL.
Case-series including 5472 patients were identified; mean dose of Mitoxantrone was 74.2 mg/m(2) (range:12-120 mg/m(2)). TRAL was diagnosed in 0.30% (1 in 333). In 34 TRAL cases, sufficient data was available to inform analysis of exposure. Onset was a median of 18.5 months following Mitoxantrone treatment (range:4-60). Acute Myelocytic Leukaemia and Acute Promyelocytic Leukaemia represented 46.4% each of the leukaemia subtypes. Six of 25 TRAL patients, where outcome was reported, died (24%). Over 80% of cases occurred in patients exposed to >60 mg/m(2), with a relative risk of 1.44 (CI95%:1.18-1.70) when comparing total dose >60 mg/m(2) against <60 mg/m(2) strongly suggesting a relationship between risk of TRAL and total dose.
在考虑使用米托蒽醌治疗多发性硬化症（MS）时，治疗相关的急性白血病（TRAL）是神经科医生和患者关注的问题。这种并发症的发生时间、风险、死亡率以及与暴露的关系仍不确定。
我们检索了有关米托蒽醌治疗MS的文献，查阅了出版物参考文献并手工检索摘要列表，以确定报告米托蒽醌治疗随访和并发症的病例系列。我们将此与我们自1997年以来治疗的250例患者的本地数据库相结合。我们还确定了所有报告的TRAL个体病例，并提取了报告TRAL暴露（剂量或mg/m²）、发生时间和结果的数据。
确定了包括5472例患者的病例系列；米托蒽醌的平均剂量为74.2mg/m²（范围：12 - 120mg/m²）。TRAL的诊断率为0.30%（333例中有1例）。在34例TRAL病例中，有足够的数据用于暴露分析。发病时间中位数为米托蒽醌治疗后18.5个月（范围：4 - 60个月）。急性髓细胞白血病和急性早幼粒细胞白血病各占白血病亚型的46.4%。在报告了结果的25例TRAL患者中，有6例死亡（24%）。超过80%的病例发生在暴露剂量>60mg/m²的患者中，将总剂量>60mg/m²与<60mg/m²进行比较时，相对风险为1.44（95%CI：1.18 - 1.70），强烈提示TRAL风险与总剂量之间存在关联。
