米卡芬净联合伏立康唑治疗血液肿瘤侵袭性真菌病患者的临床分析

目的∶探讨米卡芬净联合伏立康唑治疗血液肿瘤侵袭性真菌病（invasive fungal disease,IFD）患者的临床疗效及安全性。方法∶回顾性分析 2019年6月至2020年6月中国医学科学院肿瘤医院深圳医院接受米卡芬净联合伏立康唑抗真菌治疗的30例 IFD患者的临床资料,设为观察组,并选择同期单药应用伏立康唑抗真菌治疗的30 例IFD患者设为对照组,两组患者基数水平相当具有可比性,评价观察组和对照组的疗效及不良反应。结果∶观察组治疗中位时间16.5天（7~52天）,治疗有效率86.7%,发生不良反应率16.7%,对照组治疗中位时间22天（7~56 天）,治疗有效率63.3%,发生不良反应率20% ,观察组治疗中位时间少于对照组,治疗有效率高于对照组.差异均有统计学意义（P<0.05）。不良反应发生率略小于对照组,差异无统计学意义（P>0.05）。结论∶米卡芬净联合伏立康唑治疗IFD安全有效,值得临床选择。     

泊沙康唑预防或挽救性治疗血液病患者侵袭性真菌病的临床研究

目的 探讨泊沙康唑预防或挽救性治疗血液病患者侵袭性真菌病(IFD)的疗效及安全性.方法 回顾性分析2014年2月至2015年2月接受泊沙康唑预防或挽救性治疗IFD的25例血液病患者临床资料,患者平均年龄32.6岁(16～64岁).其中18例接受了泊沙康唑预防性治疗,7例接受了泊沙康唑挽救性治疗.结果 18例接受预防性治疗的患者在治疗期间或治疗结束后12周内,均没有出现IFD的临床表现(即无突破性真菌感染的病例),预防性治疗的平均疗程为21 d(14～35 d).7例接受挽救性治疗的患者均为伏立康唑治疗无效或不耐受者,挽救性治疗的总有效率为6/7,其中4例治愈,2例有效.所有患者中没有发现与泊沙康唑相关的明显不良反应.结论 泊沙康唑用于预防或挽救性治疗血液病患者IFD,均能够获得较好的临床疗效.     

泊沙康唑预防性抗真菌治疗在血液系统恶性肿瘤患者中的应用

目的 研究血液系统恶性肿瘤患者中预防性使用泊沙康唑抗真菌治疗的有效性和安全性.方法 回顾性分析2014年2月至2017年4月上海瑞金医院102例血液系统恶性肿瘤患者化疗期间预防性使用泊沙康唑抗真菌治疗的效果,采用Spearman进行相关性分析.结果 102例血液系统恶性肿瘤患者化疗期间,给予泊沙康唑预防性治疗后,2例(1.96%)发生侵袭性真菌感染.2例患者治疗期间发生死亡,但与泊沙康唑治疗无关.11例患者因不良反应停用泊沙康唑,不良反应导致的停药率为10.8%;2例侵袭性真菌感染抗真菌治疗失败和1例未确诊侵袭性真菌病患者停用泊沙康唑,泊沙康唑整体停药率为13.7%(14/102).泊沙康唑使用时间与住院时间、中性粒细胞缺乏时间均无相关性(rs=-0.02,P=0.853;rs=0.167,P=0.113),住院时间与中性粒细胞缺乏时间呈正相关(rs=0.448,P=0.000).结论 泊沙康唑用于血液系统恶性肿瘤患者侵袭性真菌病的预防性治疗,有效性和安全性均较佳.     

伏立康唑和伊曲康唑治疗老年恶性肿瘤合并肺部真菌感染的疗效观察

目的评价伏立康唑和伊曲康唑治疗老年恶性肿瘤合并肺部真菌感染的临床疗效和安全性。方法回顾性分析60例老年恶性肿瘤合并肺部真菌感染患者的临床资料,其中29例患者采用伏立康唑注射液治疗(伏立康唑组),31例患者采用伊曲康唑注射液治疗(伊曲康唑组),比较两种治疗方式的临床有效率和不良反应。结果伏立康唑组患者的有效率和不良反应率发生率分别为82.8%和13.8%,伊曲康唑组患者的有效率和不良反应发生率分别为70.9%和25.8%,两组患者比较,差异有统计学意义(P<0.05)。结论伏立康唑治疗老年恶性肿瘤合并肺部真菌感染的临床疗效优于伊曲康唑,安全性好,值得临床进一步推广。     

G-CSF联合GM-CSF及高剂量G-CSF治疗急性髓系白血病化疗后中性粒细胞缺乏的疗效观察

目的:探讨高剂量G-CSF方案和G-CSF联合GM-CSF方案治疗及预防急性髓细胞白血病化疗后粒细胞减少的临床疗效与安全性。方法:回顾性分析53例接受化疗的急性髓系白血病患者,对比常规剂量G-CSF、高剂量G-CSF以及G-CSF联合GM-CSF在化疗后的应用,观察中性粒细胞绝对值、中性粒细胞减少持续时间、中性粒细胞减少伴发热发生概率及各组治疗不良反应的区别。结果:高剂量G-CSF组与G-CSF联合GM-CSF组较标量G-CSF组中位ANC减少的持续时间明显缩短,中性粒细胞减少合并感染的发生率明显减少,高剂量G-CSF组与G-CSF联合GM-CSF组之间无统计学差异,三组之间安全性相仿。结论:G-CSF联合GM-CSF方案以及高剂量G-CSF方案治疗及预防急性髓细胞白血病化疗后粒细胞减少安全有效。     

伏立康唑注射液治疗血液肿瘤化疗后合并侵袭性肺部真菌感染的临床疗效

目的:分析伏立康唑注射液在血液肿瘤化疗后合并侵袭性肺部真菌感染（IPFI）经验性抗感染治疗的有效性和安全性。方法:回顾性分析2017年7月至2019年7月中国医学科学院肿瘤医院深圳医院合并IPFI的55例血液肿瘤患者应用伏立康唑注射液治疗的临床经验，其中男34例，女21例，中位年龄43.5岁（16～75岁），观察患者应用伏立康唑注射液治疗后的临床疗效和不良反应。结果:本组55例患者诊断为IPFI感染，其中确诊6例、临床诊断24例、拟诊25例，全部患者均有典型的CT影像学表现，使用伏立康唑注射液治疗的中位时间是18.5天（7～56天），应用伏立康唑注射液过程中有12例患者出现一过性幻觉，没有其它药物不良反应。最终全组患者有48例治愈、7例死亡，总有效率为87.3%。结论:伏立康唑注射液治疗IPFI疗效好，不良反应轻微，值得临床进一步应用。     

微移植联合化疗治疗老年急性髓系白血病临床观察

目的:观察微移植联合化疗治疗老年急性髓系白血病患者的临床疗效及安全性.方法:回顾性分析我院35例老年急性髓系白血病患者经单纯诱导化疗(n=16)或联合微移植(n=19)的治疗过程及转归情况.结果:微移植联合化疗组14例(73.7%)完全缓解(CR),单纯诱导化疗组6例(37.5%)CR;微移植组中性粒细胞、血小板中位恢复时间分别为11.5 d、16 d,而单纯诱导化疗组则分别为15 d、22 d(P<0.05);微移植组无重症感染及相关死亡发生,单纯化疗组因重症感染死亡3例.结论:微移植联合化疗治疗老年急性髓系白血病提高了疾病缓解率,降低了化疗相关死亡率.     

两种药物对儿童急性白血病合并真菌感染的临床疗效观察

目的探讨泊沙康唑和伊曲康唑预防及治疗儿童急性白血病合并侵袭性真菌感染的疗效。方法回顾性分析接受常规化疗的57例白血病患儿,分别应用口服伊曲康唑及泊沙康唑预防及治疗侵袭性真菌感染,分别对两组的不良反应及临床疗效进行比较。结果泊沙康唑组CR率和总有效率均高于伊曲康唑组,但差异无统计学意义(P>0.05);泊沙康唑组不良反应发生率较伊曲康唑组增高,差异无统计学意义(P>0.05),具体不良反应方面,泊沙康唑组肝功能损害发生率明显高于伊曲康唑组,差异有统计学意义(P<0.05),而在神经毒性、视觉障碍、肾功能损害及消化道反应方面,两组间差异无统计学意义(P>0.05)。结论泊沙康唑预防及治疗侵袭性真菌感染有效率高于伊曲康唑,其肝功能损害的不良反应同时也高于伊曲康唑。     

双膦酸盐联合化疗治疗多发性骨髓瘤骨并发症的临床观察

目的 比较唑来膦酸联合化疗及伊班膦酸联合化疗预防和治疗多发性骨髓瘤(MM)骨并发症的效果及其安全性.方法 选择2005年3月至2008年3月中山大学附属第一医院治疗的MM患者77例,按照用药情况分为唑来膦酸联合化疗组24例,伊班膦酸联合化疗组26例.单纯化疗组27例.结果唑来膦酸联合化疗组、伊班膦酸联合化疗组和单纯化疗组患者发生1次骨相关事件(SRE)的比例分别为25.0%、26.9%、48.1%(P=0.145).唑来膦酸联合化疗组、伊班膦酸联合化疗组发生脊柱压缩性骨折(VCF)的比例分别为4.2%和7.7%,少于单纯化疗组的14.8%(P=0.115).三组的中位首次发生SRE时间(T-SRE)分别为7.5、6.5和4.5个月(P＜0.001).唑来瞵酸联合化疗组止痛有效率为66.7%,伊班膦酸联合化疗组有效率为69.2%,单纯化疗组为29.6%,差异有统计学意义(P=0.028).唑来膦酸联合化疗组治疗后的血钙水平低于伊班膦酸联合化疗组(P=0.016),降至正常水平所需时间也较伊班膦酸联合化疗组短(P=0.04).唑来膦酸联合化疗组和伊班瞵酸联合化疗组的不良反应发牛率低,两组不良反应发生率差异无统计学意义(P＞0.05).结论 应用双瞵酸盐可减少MM患者SRE的发生率和VCF.唑来膦酸在减少VCF发生率、减轻骨痛上与伊班膦酸类似,优于单纯化疗组;唑来膦酸在降低血钙水平方面优于伊班膦酸.唑来膦酸临床应用不良反应少.患者均可耐受.     

伊曲康唑在预防淋巴瘤患儿应用利妥昔单抗治疗期间继发感染中的作用

目的 分析伊曲康唑在预防淋巴瘤患儿应用利妥昔单抗治疗期间继发感染中的应用价值.方法 将114例淋巴瘤患儿根据治疗方法不同分为对照组(n=55,利妥昔单抗治疗)与观察组(n=59,伊曲康唑+利妥昔单抗治疗).比较两组患儿治疗期间感染率、炎性因子水平及不良反应发生情况.结果 对照组患儿在利妥昔单抗治疗期间感染率高于观察组,...     

Voriconazole is effective as secondary antifungal prophylaxis in leukemia patients with prior pulmonary fungal disease: case series and review of literature

Although previous invasive fungal diseases (IFD) pose a significant risk of reactivation during successive chemotherapies in patients with acute leukemia, and secondary antifungal prophylaxis is regarded as mandatory, much remains unknown about the optimal strategy including the efficacy of voriconazole. During January 2006 and October 2008, a total of 15 patients with acute leukemia had pulmonary IFD (4 probable and 11 possible cases) before or during chemotherapy. After successful treatment of primary IFD with oral voriconazole, all of them received voriconazole during a total of 35 courses of successive chemotherapy. All but one patient successfully accomplished planned treatment without suspected IFD or significant toxicity despite profound neutropenia. We retrieved the previous reports of myelosuppressive therapies after IFD using various secondary prophylaxes, and showed that voriconazole is the most effective drug to suppress IFD relapses.     

Epidemiology and outcome of invasive fungal disease in children after hematopoietic cell transplantation or treated for malignancy: Impact of national programme of antifungal prophylaxis

The objective of the study was the analysis of incidence and outcome of invasive fungal disease (IFD) in children treated for malignancy (PHO, paediatric hematology‐oncology) or undergoing hematopoietic cell transplantation (HCT) over a period of six consecutive years in nationwide study. A total number of 5628 patients with newly diagnosed malignancies and 971 patients after HCT (741 allo‐HCT and 230 auto‐HCT) were screened for infectious complications in biennial reports. IFD incidence was lower among PHO patients: 8.8% vs 21.2% (P < .0001) and survival from IFD was better: 94.2% vs 84.1% (P < .0001). Auto‐HCT patients had lower incidence (10.9% vs 24.4%) and lower mortality than allo‐HCT patients. Introduction of national antifungal prophylaxis programme in HCT and acute leukaemia patients decreased incidence of IFD in HCT (from 23.1% to 13.4%) and AML on conventional chemotherapy (from 36% to 23%) but not in ALL patients during chemotherapy. In multivariate analysis, the incidence of IFD was higher in patients after HCT, diagnosed for ALL, AML or NHL, and in patients > 10 years old. Factors contributing to death with infection were as follows: undergoing HCT, diagnosis of acute leukaemia (ALL or AML) and duration of treatment of infection > 21 days. In conclusion, the incidence of IFD in allo‐HCT and in AML patients on chemotherapy has decreased after introduction of national programme of antifungal prophylaxis, while the incidence of IFD in ALL patients on chemotherapy did not change significantly. The outcome of IFD both in PHO and HCT patients has largely improved in comparison with historical international data.     

Amphotericin B lipid complex as prophylaxis of invasive fungal infections in patients with acute myelogenous leukemia and myelodysplastic syndrome undergoing induction chemotherapy

BACKGROUND: The optimal antifungal prophylactic regimen for patients with acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (MDS) undergoing induction chemotherapy has yet to be identified. A prospective historical control study evaluated the efficacy and safety of amphotericin B lipid complex (ABLC) in this patient population. METHODS: Newly diagnosed patients with AML or high-risk MDS who were undergoing induction chemotherapy received prophylactic ABLC 2.5 mg/kg intravenously 3 times weekly. This treatment group was compared with a historical control group that had similar baseline characteristics and received prophylactic liposomal amphotericin B (L-AmB) 3 mg/kg 3 times weekly. The primary endpoint was the incidence of documented or suspected fungal infections during and up to 4 weeks after cessation of prophylaxis. Reported adverse events were used to assess tolerability. RESULTS: The overall efficacy of antifungal prophylaxis was similar in patients who received ABLC and patients who received L-AmB (P=0.95). Among 131 ABLC-treated patients and 70 L-AmB-treated patients who were assessed for efficacy and safety, 49% of patients in each group completed therapy without developing a documented or suspected fungal infection. Documented fungal infections occurred in 5% of ABLC-treated patients and in 4% of L-AmB-treated patients. Alternative antifungal strategies were required because of persistent fever or pneumonia of unknown pathogen in 28% and 32% of ABLC-treated and L-AmB-treated patients, respectively. Grade 3 and 4 adverse events, therapy discontinuations due to adverse events, and survival rates also were similar between treatment groups. CONCLUSIONS: ABLC and L-AmB appeared to have similar efficacy and were tolerated well as antifungal prophylaxis in patients with AML and high-risk MDS who were undergoing induction chemotherapy.     

XELOX和FOLFOX4新辅助化疗方案治疗局部晚期胃癌的安全性和有效性

目的:探讨XELOX和FOLFOX4新辅助化疗方案治疗局部晚期胃癌的安全性和有效性。方法:选择我院2014年1月至2015年1月收治的局部晚期胃癌患者100例,将患者随机分为观察组（n=50）和对照组（n=50）,观察组给予XELOX方案化疗,对照组给予FOLFOX4方案化疗。观察两组患者主要临床结局和不良反应。结果:两组患者2年死亡率和复发率均无统计学差异［(32.00% vs 42.00%,P=0.300)和(70.00% vs 84.00%,P=0.096)］。观察组患者无进展生存期显著长于对照组(P=0.022)。两组患者入院时健康相关的生存质量(SF-36)差异无统计学意义(81.56±6.66 vs 81.58±7.03,P=0.988)。与对照组比较,观察组1个月和3个月后健康相关的生存质量(SF-36)均显著提高［(75.34±6.67 vs 71.66±7.35,P=0.010)和(68.24±6.44 vs 62.68±9.12,P=0.001)］。观察组恶心、呕吐、神经毒性等不良反应显著低于对照组,但手足综合征显著高于对照组,差异均有统计学意义(P＜0.05)。结论:XELOX化疗方案可延长局部晚期胃癌患者无进展生存期,不良反应较少,但手足综合征发生率较高。     

甲磺酸伊马替尼联合VDLD化疗方案治疗急性淋巴细胞白血病患儿的疗效及对T细胞免疫功能的影响

目的探讨甲磺酸伊马替尼联合VDLD化疗方案治疗急性淋巴细胞白血病患儿的疗效及对T细胞免疫功能的影响。方法将74例急性淋巴细胞白血病患儿按照随机数字表法均分为2组,对照组37例采用VDLD化疗方案治疗,观察组37例采用甲磺酸伊马替尼联合VDLD化疗方案治疗。比较2组的近期疗效、血常规及凝血指标、T细胞免疫功能变化及不良反应发生情况。结果观察组近期总有效率为91.9%,显著高于对照组的73.0%(P<0.05)。治疗前2组血常规及凝血指标差异常率比较差异均无统计学意义(P>0.05),治疗后观察组患儿血常规中血红蛋白、白细胞计数、红细胞计数、血小板计数异常率显著低于对照组(P<0.05),凝血指标中纤维蛋白原异常率显著低于对照组(P<0.05)。治疗前2组CD3+、CD4+、CD4+/CD8+比较差异无统计学意义(P>0.05),治疗后观察组患儿以上各项水平显著高于对照组(P<0.05)。2组不良反应发生率比较差异均无统计学意义(P>0.05)。结论甲磺酸伊马替尼联合VDLD化疗方案治疗急性淋巴细胞白血病患儿的近期疗效满意,能够显著改善患儿的血常规及凝血指标,提高免疫功能,并且用药安全性可靠。     

阿帕替尼治疗晚期肺腺癌的有效性和安全性研究

目的:观察甲磺酸阿帕替尼治疗晚期肺腺癌的临床疗效及不良反应。方法:回顾性分析中国人民解放军总医院2017年1月至2018年7月收治的96例二线及以上服用阿帕替尼或单纯化疗治疗晚期肺腺癌患者的疗效及安全性。以化疗组（n=35）为对照组,阿帕替尼单用（n=32）或联合替吉奥（n=29）为观察组。结果:单纯化疗组中位无进展生存期（mPFS）为3.4个月,与化疗组相比,单用阿帕替尼组mPFS为3.17个月（P=0.830）,阿帕替尼联合替吉奥组为4.8个月(P=0.015)。服用阿帕替尼后出现的不良反应主要有乏力、高血压、蛋白尿和手足综合征。大多数不良反应经积极治疗均可缓解,只有2例患者分别因严重肝损伤和严重的手足综合征停药。三组3-4级不良反应发生率分别为20.00%（7/35）、15.62%（5/32）和17.24%（5/29）,P=0.893。结论:阿帕替尼可用于晚期肺腺癌的二线及以上治疗,不良反应可控制,阿帕替尼联合替吉奥方案在晚期肺腺癌患者显示出良好的临床疗效,使患者在二线或以上继续获益。     

CLAG方案治疗复发难治急性髓系白血病的疗效观察

目的:评价CLAG方案（2-CdA+Ara-C+G-CSF）治疗复发难治急性髓系白血病的疗效及安全性。方法:回顾性分析我中心2015年6月至2016年8月应用CLAG方案治疗的12例复发难治急性髓系白血病患者。结果:12例患者均系复发难治急性髓系白血病,根据NCCN急性髓系白血病指南（2017年第1版）细胞遗传学及分子生物学标记,进行危险度分级,其中预后良好组3例,预后中等组5例,预后不良组4例。所有患者均给予1疗程CLAG方案化疗,其中8例（72.7%）达到完全缓解（CR）,2例（18.2%）达到部分缓解（PR）,总有效率（OR）90.9%。所有患者均出现Ⅲ-Ⅳ级血液学毒性,主要毒副反应为粒细胞缺乏及血小板减少所导致的感染和出血,其中肺部感染8例（72.7%）,侵袭性真菌病5例（45.5%）,革兰阴性杆菌败血症2例（18.2%）。6例患者（54.5%）发生Ⅲ-Ⅳ级出血,1例因弥漫性肺泡出血早期死亡。化疗所致恶心呕吐、肝肾毒性、口腔黏膜炎等非血液学毒性均为Ⅰ-Ⅱ级。结论:CLAG方案治疗复发难治性急性髓系白血病有效率较高。化疗所致骨髓抑制较重,但合并感染、出血可控制,非血液学毒性轻微,安全性较好,可作为复发难治急性髓系白血病挽救性治疗的首选方案。     

Treatment cost of invasive fungal disease (Ifd) in patients with acute myelogenous leukaemia (Aml) or myelodysplastic syndrome (Mds) in German hospitals

Invasive fungal disease (IFD) causes increasing morbidity and mortality in haematological cancer patients. Reliable cost data for treating IFD in German hospitals is not available. Objective of the study was to determine the institutional cost of treating the IFD. Data were obtained by retrospective chart review in German hospitals. Patients had either newly diagnosed or relapsed acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS). Direct medical cost was calculated from hospital provider’s perspective. A total of 108 patients were enrolled at 5 tertiary care hospitals, 36 IFD patients and 72 controls. The vast majority of IFD patients (74%) were diagnosed with invasive aspergillosis. On average, the hospital stay for IFD patients was 12 days longer than in control patients. All patients in the IFD group and 89% of patients in the control group received antifungal drugs. Mean direct costs per patient were €51 517 in the IFD group and €30 454 in the control group. Incremental costs of €21 063 were dominated by cost for antifungal drugs (36%), hospital stay (32%) and blood products (23%). From the perspective of hospitals in Germany the economic burden of IFD in patients with AML or MDS is substantial. Therefore, prevention of IFD is necessary with respect to both clinical and economic reasons.