Koteda Satoko, Nomura Kei, Hashiguchi Michitoshi, Kawaguchi Kuniki, Oku Eijiro, Osaki Koichi, Nakamura Takayuki, Mouri Fumihiko, Imamura Rie, Seki Ritsuko, Nagafuji Koji, Makimura Koichi, Okamura Takashi
Department of Medicine, Kurume University School of Medicine, Japan.
Rinsho Ketsueki. 2013 Mar;54(3):311-5.
A 62-year-old woman with acute lymphoblastic leukemia in first complete remission was treated with unrelated cord blood transplantation, but exhibited primary graft failure. She then underwent HLA-haploidentical peripheral blood stem cell transplantation from her daughter. The conditioning regimen consisted of fludarabine 30 mg/m(2)/day for 6 days, intravenous busulfan 3.2 mg/kg/day for 2 days, and thymoglobulin 1 mg/kg/day for 2 days. Voriconazole was administered to prevent fungal infections. The patient achieved prompt hematopoietic recovery. Fever was observed 21 days after the second transplant, followed by sigmoid colon perforation and a liver space occupying lesion (SOL). A filamentous fungus was detected in a percutaneous biopsy of the liver SOL. In spite of changing the antifungal drug from voriconazole to liposomal amphotericin B, the patient died on day 41. The fungus was identified as Mucor indicus, a type of zygomycete. Although Mucor indicus inhabits soil, an infectious disease is extremely rare, and breakthrough infection after voriconazole prophylaxis had not been reported until now. It is mandatory to consider preventive antifungal treatment for drug-resistant fungal infectious diseases in patients after neutrophilic recovery with a strongly immunocompromised state after a HLA-haploidentical transplant.
一名62岁处于首次完全缓解期的急性淋巴细胞白血病女性接受了非亲缘脐血移植治疗，但出现了原发性移植物功能衰竭。随后她接受了来自其女儿的HLA单倍型相合外周血干细胞移植。预处理方案包括氟达拉滨30mg/m²/天，共6天；静脉注射白消安3.2mg/kg/天，共2天；以及抗胸腺细胞球蛋白1mg/kg/天，共2天。给予伏立康唑预防真菌感染。患者造血功能迅速恢复。第二次移植后21天出现发热，随后出现乙状结肠穿孔和肝脏占位性病变（SOL）。在肝脏SOL的经皮活检中检测到丝状真菌。尽管将抗真菌药物从伏立康唑换为脂质体两性霉素B，患者仍在第41天死亡。该真菌被鉴定为印度毛霉，一种接合菌。尽管印度毛霉存在于土壤中，但其感染性疾病极为罕见，且此前尚未有关于伏立康唑预防后突破性感染的报道。对于HLA单倍型相合移植后中性粒细胞恢复且免疫状态严重受损的患者，必须考虑针对耐药真菌传染病的预防性抗真菌治疗。
