儿童异基因造血干细胞移植后真菌感染

Invasive Fungal Infection after Allogeneic Hematopoietic Stem Cell Transplantation in Children

目的观察儿童异基因造血干细胞移植（Allo-HSCT）后侵袭性真菌感染（IFIs）的发生情况,对其发生率、临床表现、危险因素及其预后进行分析,为临床能够更好的预防和治疗IFIs提供参考。方法收集Allo-HSCT患儿41例。男24例,女17例;年龄2-13岁。重型β珠蛋白生成障碍贫血26例,肾上腺脑白质营养不良1例,其他血液病14例。骨髓移植20例,外周血干细胞移植19例,骨髓加脐血移植2例。血缘相关供者移植14例,非血缘相关供者移植27例。预处理方案以白消安加环磷酰胺加抗胸腺免疫球蛋白为主,部分加用全身放疗、氟达拉滨、塞替哌或沙可来新。移植物抗宿主病（GVHD）的预防以环孢素加霉酚酸酯为基础。痰、血、咽拭子、尿、大便培养检测41例患儿IFIs发生情况。结果41例患儿Allo-HSCT后,5例患儿发生了IFIs,IFIs的总发生率为12.2%（5/41例）。其中确诊病例1例（2.4%）,临床诊断病例2例（4.9%）,拟诊病例2例（4.9%）。IFIs发生时间为移植术第9-120天,3例（60%）发生在移植1个月内。曲霉菌感染2例,念珠菌感染1例。大剂量激素治疗组IFIs发生率高于未接受大剂量激素治疗组（χ^2=8.201P=0.004）;含有塞替哌预处理方案患儿IFIs发生率高于未包含的患儿组（χ^2=9.549P=0.002）。不同年龄、基础疾病、移植方式、GVHD的发生患儿间IFIs发生率比较差异无统计学意义。治疗总有效率为40%,确诊病例的有效率为100%,临床诊断病例的有效率为0,拟诊病例的有效率为50%。结论IFIs是Allo-HSCT的重要并发症,大剂量激素治疗和含有塞替哌的预处理为发生IFIs的危险因素。曲霉菌和念珠菌是Allo-HSCT最常见致病菌,以曲霉菌为主。

Objective To explore the incidence, clinical status, risk factors and outcomes of invasive fungal infections （IFIs） after allogeneic hematopoietic stem cell transplantation （ Allo - HSCT） in pediatric patients. Methods Forty - one Patients who were underwent Allo - HSCT were selected from 2005 to 2006. Of 41 patients, 24 were boys and 17 were girls, aged 2 - 13 years old, Twenty - six cases with 15 - thalassemia, 1 case with adrenoleukodystrophy, and the left 14 cases with other hematologic disorders. Twenty patients underwent bone marrow transplantation, 19 patients underwent peripheral blood stem cell transplantation,2 patients underwent bone marrow transplantation and cord blood transplantation, Fourteen patients received Allo - HSCT from HLA - matched sibling donors or HLA mis - matched parents, 27 patients received Allo - HSCT from unrelated donors, Based on different types of transplant, patients were conditioned with busulfan, cyclophospha- mide and Anti -thymocyte immune globulin. Fludalabine, total body irration, thiotepa or melphalan was used additionly in some cases. Cyclosporine A and mycophnolate mofetil were used as prophylaxis of graft versus host disease （GVHD）. Results IFIs was observed in 5 cases （5/41 cases,12.2% ） ,this comprised cases of proven,probable and possible IFIs at rates of 2.4% ,4.9% ,4, 9%. The time of IFIs was 9 - 120 d after transplantation, the majority of IFIs in 3/5 cases （60%） children occurred within the first month. The difference of IFIs between pa- tients who recived high - dose corticosterold and those with no or conventional - dose corticosteroid was significant （ Χ^2 = 8.201 P = 0. 004） ;Regarding conditioning regimens, the IFIs of patients who with Thiotepa （TT） was significanthy higher than that of compared with those without TT（ Χ^2 = 9.549 P = 0.002）. The total effective rate was 40%. The effective rates of the patients with confimed diagnosis, clinical diagnosis,and with recommended diagnosis respectively were 100% ,0 and 50% respectively. Conclusions IFIs is an important complication after Allo - HSCT, and the high - dose corticosteroid therapy and conditioning regimens with TT are the risky factors for IFIs. Aspergillus is the main pathogen bacteria.