Pagano Livio, Mele Luca, Fianchi Luana, Melillo Lorella, Martino Bruno, D'Antonio Domenico, Tosti Maria Elena, Posteraro Brunella, Sanguinetti Maurizio, Trapè Giulio, Equitani Francesco, Carotenuto Mario, Leone Giuseppe
Department of Hematology, Catholic University, largo Francesco Vito 1, 00168 Rome, Italy.
Haematologica. 2002 May;87(5):535-41.
To evaluate the characteristics of patients affected by hematologic malignancies who developed a chronic disseminated candidiasis (CDC), and to ascertain the factors that influenced the outcome, in a retrospective study conducted between January 1990 and December 2000, in 4 Hematology Divisions.
CDC was diagnosed by clinical features combined with radiological and/or histologic and/or microbiological data.
Twenty-eight patients (male/female 14/14; average age 42 years, range 12-67) developed a CDC. Twenty had acute myeloid leukemia, 5 had acute lymphocytic leukemia and 3 had non-Hodgkin's lymphoma. All patients received chemotherapy, including cytarabine for 21 of them (75%). Before the infection, 22 patients (79%) were neutropenic (absolute neutrophil count < 0.5 x 10(9)/L) for an average of 20 days (8-36), but at CDC diagnosis only 3 patients (11%) were neutropenic. Twenty-two patients (75%) received antifungal prophylaxis for an average of 15 days (10-60). Before diagnosis of CDC, 9 patients (32%) had a candidemia. The sites compromised by CDC were: liver in 27 patients (96%) and/or spleen in 11 patients (38%). Ten patients had other organs involved: lung in 6 patients (21%), kidney in 4 patients (14%), other sites 2 patients (7%). Abdominal ultrasonography was positive in 96% of patients (27/28), and abdominal computed tomography-scan was positive in 100% of cases in which it was performed (21/21). Liver biopsy was positive in 10/15 patients (67%). The main signs and symptoms were: fever 86%, abdominal pain 54%, diarrhea 32%, tenderness 25%, vomiting 25%, jaundice 29%, dysphagia 7%. Among chemical analyses, the most sensitive test was alkaline phosphatase, with a 3-5-fold increase in 24 patients (86%); an increase of liver transaminases and g-glutamyl transferase was observed in less than 50% of patients. By 30 days after diagnosis 4 patients had died, 1 from infection, and 3 progression of the hematologic malignancy without signs of active CDC. Within 3 months from diagnosis 14 out of the remaining 24 patients (58%) received further chemotherapy: in particular, 2 patients underwent transplantation procedures.
In our experience CDC is not a fatal complication of patients with hematologic malignancy, on the contrary to that observed for other fungal infections (i.e. aspergillosis, candidemia), characterized by a higher mortality rate. The major problem of this fungal complication is correlated to the delay in the following treatment for the hematologic malignancy with a high risk of progression of malignancy.
在1990年1月至2000年12月期间,于4个血液科开展的一项回顾性研究中,评估发生慢性播散性念珠菌病(CDC)的血液系统恶性肿瘤患者的特征,并确定影响预后的因素。
根据临床特征结合放射学和/或组织学和/或微生物学数据诊断CDC。
28例患者(男/女14/14;平均年龄42岁,范围12 - 67岁)发生了CDC。其中20例患有急性髓性白血病,5例患有急性淋巴细胞白血病,3例患有非霍奇金淋巴瘤。所有患者均接受了化疗,其中21例(75%)接受了阿糖胞苷治疗。感染前,22例患者(79%)出现中性粒细胞减少(绝对中性粒细胞计数<0.5×10⁹/L),平均持续20天(8 - 36天),但在CDC诊断时仅有3例患者(11%)为中性粒细胞减少。22例患者(75%)接受了平均15天(10 - 60天)的抗真菌预防。在CDC诊断前,9例患者(32%)发生了念珠菌血症。受CDC累及的部位有:27例患者(96%)肝脏和/或11例患者(38%)脾脏。10例患者有其他器官受累:6例患者(21%)肺部,4例患者(14%)肾脏,2例患者(7%)其他部位。腹部超声检查96%的患者(27/28)呈阳性,腹部计算机断层扫描在进行检查的所有病例(21/21)中均呈阳性。肝活检15例患者中有10例(67%)呈阳性。主要体征和症状有:发热86%,腹痛54%,腹泻32%,压痛25%,呕吐25%,黄疸29%,吞咽困难7%。在化学分析中,最敏感的检测指标是碱性磷酸酶,24例患者(86%)升高3 - 5倍;不到50%的患者观察到肝转氨酶和γ-谷氨酰转移酶升高。诊断后30天内,4例患者死亡,1例死于感染,3例死于血液系统恶性肿瘤进展且无活动性CDC迹象。诊断后3个月内,其余24例患者中有14例(58%)接受了进一步化疗:特别是2例患者接受了移植手术。
根据我们的经验,与其他真菌感染(如曲霉病、念珠菌血症)不同,CDC并非血液系统恶性肿瘤患者的致命并发症,后者具有较高的死亡率。这种真菌并发症的主要问题与血液系统恶性肿瘤后续治疗的延迟相关,存在恶性肿瘤进展的高风险。