Secondary antifungal prophylaxis in paediatric allogeneic haematopoietic stem cell recipients
Secondary antifungal prophylaxis in paediatric allogeneic haematopoietic stem cell recipients
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DOI：
10.1093/jac/dkm521
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发表时间：
2008-03-01
影响因子：
5.2
通讯作者：
Groll, Andreas H.
中科院分区：
文献类型：
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作者：
Allinson, Katherine;Kolve, Hedwig;Groll, Andreas H.
目的：侵袭性肺曲霉菌病（IPA）是急性白血病患者感染性疾病的一个重要原因。虽然先前的IPA不是随后的异基因造血干细胞移植（HSCT）的禁忌症，但在粒细胞减少症和免疫抑制期间的管理仍然具有挑战性。（11-18岁）急性白血病患者和既往可能（4）或很可能（7）IPA病史患者接受脂质体阿朴霉素B治疗（LAMB; 1 mg/kg，每日一次），从预处理方案开始直至植入和能够口服药物，随后口服伏立康唑（200 mg，每日两次）直至风险期结束。9例患者有一个很好的部分反应（> 50%减少肺浸润）和两个有一个完整的反应之前HSCT.Results：静脉治疗LAMB的中位持续时间为30天（范围，19-36），其次是口服伏立康唑的中位数为152天（范围，19-210）。1例患者提前停用LAMB，2例和2例患者分别因不良事件/新禁忌症暂时或永久停用伏立康唑。在移植后+180天，8名患者存活，6名完全，1名接近完全和持续的肺浸润消退;除1名外，所有患者均持续血液学缓解。3例患者死于复发性白血病（2例）或难治性移植物衰竭（1例）;其中1例患者保持完全缓解，2例患者死于继发性可能（1例）或很可能（1例）IPA。这两名患者已停止伏立康唑早期和发展IPA在肺领域参与在primary epission.Conclusions：这一前瞻性儿科系列支持的概念，即二级抗真菌预防可能或可能的IPA可以安全地实现在同种异体造血干细胞移植。在没有慢性移植物抗宿主病的情况下，突破性感染似乎与复发性白血病/移植物衰竭和植入后预防的持续时间较短相关。
Objectives: Presumed or proven invasive pulmonary aspergillosis (IPA) is an important cause of infectious morbidity in patients with acute leukaemia. Although prior IPA is not a contraindication for subsequent allogeneic haematopoietic stem cell transplantation (HSCT), its management during granulocytopenia and immunosuppression remains challenging.Patients and methods: In the absence of an evidence-based approach, 11 adolescents (11-18 years) with acute leukaemia and a history of antecedent possible (4) or probable (7) IPA received liposomal amphotericin B (LAMB; 1 mg/kg once a day) from the start of the conditioning regimen until engraftment and ability to take oral medication, followed by oral voriconazole (200 mg twice a day) until the end of the at-risk period. Nine patients had a good partial response (> 50% reduction in pulmonary infiltrates) and two had a complete response prior to HSCT.Results: The median duration of intravenous treatment with LAMB was 30 days (range, 19-36), followed by a median of 152 days (range, 19-210) of oral voriconazole. LAMB was discontinued early in one patient and voriconazole was transiently or permanently discontinued due to adverse events/new contraindications in two and two patients, respectively. At +180 days post-transplant, eight patients were alive, six with complete, and one each with near complete and ongoing resolution of pulmonary infiltrates; all but one were in continuing haematological remission. Three patients had succumbed either to recurrent leukaemia (two) or refractory graft failure (one); whereas one of these patients had maintained a complete response, two died with secondary possible (one) or probable (one) IPA. Both patients had discontinued voriconazole early and developed IPA in lung areas involved during the primary episode.Conclusions: This prospective paediatric series supports the notion that secondary antifungal prophylaxis for possible or probable IPA can be safely achieved in allogeneic HSCT. In the absence of chronic graft-versus-host disease, breakthrough infection appeared to be associated with recurrent leukaemia/graft failure and shorter duration of post-engraftment prophylaxis.