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高剂量粒细胞输注对念珠菌血症癌症患者的影响:491例念珠菌属血流感染病例的回顾性病例对照分析

Impact of high-dose granulocyte transfusions in patients with cancer with candidemia: retrospective case-control analysis of 491 episodes of Candida species bloodstream infections.

作者信息

Safdar Amar, Hanna Hend A, Boktour Maha, Kontoyiannis Dimitrios P, Hachem Ray, Lichtiger Benjamin, Freireich Emil J, Raad Issam I

机构信息

Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.

出版信息

Cancer. 2004 Dec 15;101(12):2859-65. doi: 10.1002/cncr.20710.

Abstract

BACKGROUND

The efficacy and feasibility of donor granulocyte transfusion therapy (GTX) have changed considerably over the past four decades. The authors sought to determine the impact of high-dose (approximately 5.5 x 10(10) cells) GTX in patients with candidemia.

METHODS

The authors' case-control retrospective analysis comprised 491 consecutive patients treated at The University of Texas M. D. Anderson Cancer Center (Houston,TX) from 1993 to 2000. The cohort included 29 patients with Candida species bloodstream infection who had received GTX and 462 who had not.

RESULTS

Both groups were comparable in age, gender, APACHE II score, recent chemotherapy received, broad-spectrum antibiotics, systemic corticosteroids, radiotherapy, intravascular catheter, and concordant antifungal therapy (P > or = 0.1). The patients who received GTX compared with those who did not had a higher incidence of underlying leukemia (86% vs. 29%, P <0.001), persistent neutropenia (59% vs. 18%, P <0.001), non-Candida albicans candidemia (Candida glabrata, 35%; Candida krusei, 31%: 90% vs. 67%, P=0.01), and breakthrough invasive mycosis (62% vs. 23%, P <0.001). Neutropenia was more prolonged in patients who received GTX (28 vs. 10 days, P <0.001). Also, more of the patients who received GTX had received hematopoietic stem cell transplantations (28% vs. 13%, P = 0.03), exposure (within 4 weeks) to antifungals (79% vs. 38%, P <0.001), and stays in critical care units (62% vs. 40%, P=0.02). The overall attributable mortality rate for 25 evaluable recipients of GTX was 48% (n=12), compared with 45% (n=115) of 254 evaluable patients in the control group (P=0.5). Of the 158 patients with leukemia, 25 (16%) had received GTX. In patients with leukemia, more of those who had received GTX experienced disseminated candidiasis (44% vs. 26%; P <0.07) and persistent neutropenia (68% vs. 43%, P <0.02), had candidemia that was more prolonged (> 72 hours, P <0.02), and had more stays in critical care units (68% vs. 44%, P <0.03). On the bases of a reduced multivariate model, a significantly increased risk of death was found for patients with hematopoietic stem cell transplantation (odds ratio [OR]=2.51; 95% confidence interval [95% CI], 0.99-6.31; P <0.05), for patients with persistent neutropenia (OR=4.57; 95% CI, 1.99-10.47; P <0.0003), and for patients with leukemia who also had prolonged candidemia (OR=3.59; 95% CI, 1.61-7.98; P <0.002), disseminated candidiasis (OR=5.19; 95% CI, 2.17-12.42; P <0.0002), or non-C. albicans candidemia (OR=5.02; 95% CI, 1.07-23.64; P <0.04). In patients with leukemia, death was attributable to candidemia in 50% of the GTX recipients, compared with 59% of the non-GTX patients who had received antifungal therapy alone (P=0.4).

CONCLUSIONS

Despite the presence of multiple predictors of increased mortality, high-dose GTX therapy in these high-risk patients with cancer was associated with better than expected survival rates.

摘要

背景

在过去的四十年里,供体粒细胞输注疗法(GTX)的疗效和可行性发生了很大变化。作者试图确定高剂量(约5.5×10¹⁰个细胞)GTX对念珠菌血症患者的影响。

方法

作者的病例对照回顾性分析包括1993年至2000年在德克萨斯大学MD安德森癌症中心(休斯顿,德克萨斯州)接受治疗的491例连续患者。该队列包括29例接受GTX的念珠菌属血流感染患者和462例未接受GTX的患者。

结果

两组在年龄、性别、急性生理与慢性健康状况评分系统II(APACHE II)评分、近期接受的化疗、广谱抗生素、全身性皮质类固醇、放疗、血管内导管以及一致的抗真菌治疗方面具有可比性(P≥0.1)。与未接受GTX的患者相比,接受GTX的患者潜在白血病的发生率更高(86%对29%,P<0.001)、持续性中性粒细胞减少症的发生率更高(59%对18%,P<0.001)、非白色念珠菌念珠菌血症(光滑念珠菌,35%;克柔念珠菌,31%:90%对67%,P=0.01)以及突破性侵袭性真菌病的发生率更高(62%对23%,P<0.001)。接受GTX的患者中性粒细胞减少症持续时间更长(28天对10天,P<0.001)。此外,接受GTX的患者中更多人接受了造血干细胞移植(28%对13%,P = 0.03)、(在4周内)接触抗真菌药物(79%对38%,P<0.001)以及入住重症监护病房(62%对40%,P=0.02)。25例可评估的GTX接受者的总体归因死亡率为48%(n = 12),而对照组254例可评估患者的死亡率为45%(n = 115)(P = 0.5)。在158例白血病患者中,25例(16%)接受了GTX。在白血病患者中,接受GTX的患者更多出现播散性念珠菌病(44%对26%;P<0.07)和持续性中性粒细胞减少症(68%对43%,P<0.02),念珠菌血症持续时间更长(>72小时,P<0.02),并且入住重症监护病房的次数更多(68%对44%,P<0.03)。基于简化的多变量模型,发现接受造血干细胞移植的患者死亡风险显著增加(比值比[OR]=2.51;95%置信区间[95%CI],0.99 - 6.31;P<0.05),持续性中性粒细胞减少症患者(OR = 4.57;95%CI,1.99 - 10.47;P<0.0003),以及患有白血病且念珠菌血症持续时间延长的患者(OR = 3.59;95%CI,1.61 - 7.98;P<0.002)、播散性念珠菌病患者(OR = 5.19;95%CI,2.17 - 12.42;P<0.0002)或非白色念珠菌念珠菌血症患者(OR = 5.02;95%CI,1.07 - 23.64;P<0.04)。在白血病患者中,50%的GTX接受者的死亡归因于念珠菌血症,而仅接受抗真菌治疗的非GTX患者中这一比例为59%(P = 0.4)。

结论

尽管存在多种死亡率增加的预测因素,但在这些高危癌症患者中,高剂量GTX治疗与优于预期的生存率相关。

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