Voriconazole for both successful treatment of disseminated Trichosporon asahii infection and subsequent cord blood transplantation in an infant with acute myelogenous leukemia
Voriconazole for both successful treatment of disseminated Trichosporon asahii infection and subsequent cord blood transplantation in an infant with acute myelogenous leukemia
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DOI：
10.1038/bmt.2010.96
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发表时间：
2011-02
影响因子：
4.8
通讯作者：
K. Kudo;K. Terui;S. Sasaki;T. Kamio;T. Sato;E. Ito
中科院分区：
文献类型：
--
作者：
K. Kudo;K. Terui;S. Sasaki;T. Kamio;T. Sato;E. Ito
播散性丝孢酵母菌感染是一种罕见但危及生命的真菌感染，通常见于免疫功能低下的宿主，尤其是血液系统恶性肿瘤患者。1播散性毛孢子菌病的预后通常较差，死亡率约为80%。1尽管先前的报告表明伏立康唑（VRCZ）是有效的，但1-3关于VRCZ治疗儿科患者的临床数据有限。即使这种感染被成功治疗，后续的化疗和/或造血干细胞移植（HSCT）将是具有挑战性的。据我们所知，还没有关于播散性毛孢子菌病后HSCT成功的报道。在这里，我们报告使用VRCZ成功治疗了弥散性阿萨希毛孢子菌感染，并随后对患有急性髓细胞白血病的婴儿进行了脐带血移植。2007年3月，一名患有t（1; 22）（p13; q13）异常的急性巨核细胞白血病的5个月大女孩开始接受诱导化疗，并获得CR。她在第一个疗程的巩固化疗后继续CR，并于2007年6月接受了第二个疗程的阿糖胞苷，米托蒽醌和依托泊苷。在开始化疗后12天，她的白细胞计数降至0.05 109/L，并出现高烧。患者接受帕尼培南/倍他米隆、米诺环素、磷氟康唑和粒细胞CSF治疗，第二天发热消退。在第一次发热后4天，她再次发热，面部和躯干出现数个丘疹（第0天）。抗生素改为万古霉素和头孢匹罗，但高热持续。在第2天，报告她从第0天开始的血培养对酵母样真菌呈阳性，并将米卡芬净添加到化疗中。然而，高烧持续，第3天出现轻度呼吸窘迫。在第4天，酵母样真菌被鉴定为丝孢酵母属（Trichosporon species）和T.随后用PCR检测asahii DNA。结果表明，5-氟胞嘧啶、氟康唑、咪康唑、伊曲康唑、米卡芬净和VRCZ对T. asahii分离物的最低抑菌浓度分别为2、> 64、4、0.5、1、> 16和0.125 μg/mL。血清隐球菌抗原阳性，改为静注VRCZ（第1天6 mg/kg，每12 h 1次，第2天4 mg/kg，每12 h 1次）。虽然第6天和第8天血清β-D-葡聚糖呈一过性阳性，但患者的血培养在开始VRCZ治疗后变为阴性，第10天体温降至低烧，呼吸窘迫和呼吸窘迫改善。第11天的VRCZ血浆谷浓度为1.07 μg/mL。在第14天，她的白细胞计数和中性粒细胞计数分别增加到大于1.0 109/L和0.5 109/L，在第19天，她的低热消退。此时，血清隐球菌抗原仍为阳性，从第32天开始口服VRCZ（每12 h 4 mg/kg）。2007年8月，在丝孢酵母菌感染发作后6周，由于患有t（1; 22）（p13; q13）的婴儿AML预后不良，患者按计划接受了无关脐带血移植。在第109天，VRCZ给药从口服改为iv（4 mg/kg，每12 h一次），以预防丝孢酵母菌感染。移植前预处理包括在第208 - 205天iv BU 4 mg/kg/天（总剂量16 mg/kg）和在第204和203天iv美法仑70 mg/m2/天（总剂量140 mg/m2）。她接受了6/6 HLA匹配的脐带血，其中含有1.2 108/kg的总有核细胞和4.3 105/kg的CD 34+细胞。他克莫司和...
Disseminated Trichosporon infection is an uncommon but life-threatening fungal infection usually observed in immunocompromised hosts, especially in patients with hematological malignancies. 1 The outcome of disseminated trichosporonosis is usually poor, with a mortality rate of approximately 80%. 1 Although previous reports suggest that voriconazole (VRCZ) is efficacious, 1–3 clinical data on VRCZ therapy in pediatric patients are limited. 3, 4 Even if this infection is successfully treated, subsequent chemotherapy and/or hematopoietic SCT (HSCT) will be challenging. To our knowledge, there have been no reports on successful HSCT after disseminated trichosporonosis. Here, we report using VRCZ for both successful treatment of disseminated Trichosporon asahii infection and for subsequent cord blood transplantation in an infant with AML. In March 2007, a 5-month-old girl with acute megakaryoblastic leukemia with t (1; 22)(p13; q13) abnormality was started on induction chemotherapy and achieved a CR. She continued in CR after the first course of consolidation chemotherapy and received the second course consisting of cytarabine, mitoxantrone and etoposide in June 2007. At 12 days after the initiation of chemotherapy, her WBC count decreased to 0.05 Â 109/L and she developed high fever. She was treated with panipenem/betamipron, minocycline, fosfluconazole and granulocyte CSF, and her fever subsided on the following day. At 4 days after the first episode of fever, she became febrile again and several erythematous papules appeared on her face and trunk (day 0). The antibiotics were changed to vancomycin and cefpirome, but high fever persisted. On day 2, her blood culture from day 0 was reported to be positive for a yeastlike fungus and micafungin was added to the chemotherapy. However, high fever persisted and she had mild respiratory distress on day 3. On day 4, the yeast-like fungus was identified as Trichosporon species and T. asahii DNA was subsequently detected by PCR. The minimum inhibitory concentrations of amphotericin B, 5-fluorocytosine, fluconazole, miconazole, itraconazole, micafungin and VRCZ against the T. asahii isolate were 2,> 64, 4, 0.5, 1,> 16 and 0.125 μg/mL, respectively. Serum cryptococcal Ag was found to be positive and antifungal agents were changed to iv VRCZ (6 mg/kg every 12 h on the first day and 4mg/kg every 12h on the following days). Although serum β-D-glucan was transiently positive on day 6 and day 8, the patient’s blood cultures became negative afterVRCZ therapy was begun and her temperature decreased to a low-grade fever with improvement in exanthema and respiratory distress on day 10. The VRCZ trough plasma concentration on day 11 was 1.07 μg/mL. On day 14, her WBC count and neutrophil count increased to greater than 1.0 Â 109/L and 0.5 Â109/L, respectively, and on day 19 her low-grade fever subsided. At this time, the serum cryptococcal Ag was still positive and VRCZ was administered orally from day 32 (4 mg/kg every 12 h). In August 2007, 6 weeks after the onset of Trichosporon infection, the patient underwent unrelated cord blood transplantation as scheduled because of the poor prognosis of infant AML with t (1; 22)(p13; q13). On day À9, VRCZ administration was changed from oral to iv (4 mg/kg every 12h) for prophylaxis against Trichosporon infection. Pretransplant conditioning consisted of iv BU 4mg/kg/day on days À8 to À5 (total dose 16mg/kg) and melphalan 70 mg/m2/day on days À4 and À3 (total dose 140mg/m2). She received 6/6 HLA-matched cord blood containing 1.2 Â 108/kg total nucleated cells and 4.3 Â105/kg CD34þ cells. Tacrolimus and …