El-Beshlawy Amal M, El-Alfy Mohsen S, Sari Teny T, Chan Lee L, Tricta Fernando
Hematology Department, Pediatric Hospital, Cairo University, Cairo, Egypt.
Eur J Haematol. 2014 Apr;92(4):337-40. doi: 10.1111/ejh.12241. Epub 2014 Jan 30.
Approximately 6% of patients with thalassemia receiving deferiprone develop neutropenia. Present practice is to monitor absolute neutrophil count (ANC) weekly and to interrupt treatment at the first sign of neutropenia, lest continuation lead to progressive neutrophil reduction. In a 6-month study evaluating the safety and efficacy of a liquid form of deferiprone in 100 children, ANC was initially checked weekly for all patients. For individuals experiencing mild neutropenia, deferiprone was continued but monitoring was increased to daily until resolution. Therapy was to be suspended only if the episode was prolonged or if it worsened. Four patients experienced single episodes of mild neutropenia, and two others each experienced two episodes. All eight episodes resolved within 4-7 d despite continued therapy. (One patient later developed agranulocytosis and had treatment terminated.) This study showed that not all cases of mild neutropenia during deferiprone therapy develop into agranulocytosis, and suggests that many may not be caused by deferiprone. Transient declines in ANC to levels defined as neutropenic are common even in healthy individuals, particularly children; and it could be that the frequent monitoring of ANC mandated during deferiprone therapy may reveal cases of transient neutropenia that would otherwise have gone undetected and resolved on their own without clinical consequences. In patients with thalassemia, several factors increase the probability of a transient fall in ANC. These findings raise the question of whether deferiprone should be routinely stopped in cases of mild neutropenia, provided that such patients have their ANC monitored more frequently during the neutropenic episode.
接受去铁酮治疗的地中海贫血患者中约6%会出现中性粒细胞减少。目前的做法是每周监测绝对中性粒细胞计数(ANC),并在中性粒细胞减少的首个迹象出现时中断治疗,以免继续治疗导致中性粒细胞持续减少。在一项为期6个月的研究中,评估了100名儿童使用液体形式去铁酮的安全性和有效性,所有患者最初每周检查一次ANC。对于出现轻度中性粒细胞减少的个体,继续使用去铁酮,但监测频率增加至每日一次,直至恢复正常。只有在病情持续或恶化时才暂停治疗。4名患者经历了单次轻度中性粒细胞减少发作,另外两名患者各经历了两次发作。尽管继续治疗,所有8次发作均在4 - 7天内缓解。(一名患者后来发展为粒细胞缺乏症并终止了治疗。)这项研究表明,去铁酮治疗期间并非所有轻度中性粒细胞减少病例都会发展为粒细胞缺乏症,并提示许多病例可能并非由去铁酮引起。即使在健康个体,尤其是儿童中,ANC短暂下降至定义为中性粒细胞减少的水平也很常见;可能是去铁酮治疗期间要求的频繁ANC监测发现了一些短暂性中性粒细胞减少病例,否则这些病例可能未被发现并自行缓解而无临床后果。在地中海贫血患者中,有几个因素会增加ANC短暂下降的可能性。这些发现提出了一个问题,即在轻度中性粒细胞减少的情况下,如果此类患者在中性粒细胞减少发作期间更频繁地监测ANC,是否应常规停用去铁酮。