急性白血病患者肺部曲霉菌病的手术治疗及再发预防

 目的 报告4例合并肺部曲霉菌病的急性白血病病例。方法 4例患者均接受外科手术切除病灶,手术标本行常规HE染色。3例患者手术后接受抗真菌药物的再发预防。结果 4例患者均成功切除肺部曲霉菌球,组织病理检查的结果证实为曲霉菌感染,预防治疗使得所有患者成功接受进一步的化疗或造血干细胞移植。结论 手术治疗是合并肺部曲霉菌感染的急性白血病患者重要的辅助治疗手段,积极的再发预防可以保护患者接受进一步的化疗或造血干细胞移植。     

儿童急性淋巴细胞白血病化疗后合并结核性脑膜炎一例并文献复习

目的 探讨儿童急性淋巴细胞白血病(ALL)化疗后合并结核性脑膜炎(TBM)的临床特点及诊治.方法 回顾性分析福建医科大学附属协和医院2014年9月收治的1例ALL维持化疗中合并肺结核及TBM患儿的临床资料,并复习相关文献.结果 患儿,男性,11岁,确诊ALL 27个月,维持化疗中,出现中性粒细胞缺乏伴发热,予抗感染、抗真菌及甲泼尼龙治疗后,体温一度正常;1个月后再次发热,伴咳嗽、头痛,予抗感染、抗真菌治疗无好转,头痛加剧,并出现颈项强直,肺部CT示上肺及下肺背段炎症,脑脊液结核TB-DNA、结核分枝杆菌培养均阳性,确诊继发性肺结核、结核性脑膜炎,予规则抗结核治疗1.5年,病情治愈.结论 儿童ALL合并TBM的早期诊断是难点,及时、长疗程抗结核治疗,适当兼顾白血病化疗,仍可取得较好的抗结核病疗效,且不影响白血病预后.     

儿童白血病侵袭性肺真菌感染六例临床分析

 【摘要】　目的　探讨儿童白血病侵袭性肺真菌感染的临床特点及治疗方法。方法　6例急性淋巴细胞白血病患儿在化疗过程中出现中性粒细胞缺乏,引发侵袭性肺真菌感染,6例均经临床诊断,予早期经验性抗真菌治疗。结果　4例治愈,1例因经济原因放弃治疗,1例死亡。结论　儿童白血病侵袭性肺真菌感染应早期给予经验性抗真菌治疗,卡泊芬净安全性好,疗效可靠,可作为一线用药。     

毛细胞白血病合并肺孢子菌肺炎和Sweet综合征一例

目的 探讨毛细胞白血病同时合并肺孢子菌肺炎和Sweet综合征的临床特点、诊断治疗及相互关系.方法 分析1例毛细胞白血病合并肺孢子菌肺炎和Sweet综合征的诊治过程并复习文献.结果 患者为51岁男性,以毛细胞白血病入院治疗,住院期间持续发热、咳嗽、呼吸困难,皮肤散在红色斑疹.肺部CT提示多发片状、斑片状及结节状实变影,边缘模糊以及胸腔积液；经广谱抗生素、抗真菌（不含棘白菌素类药）治疗无效,使用磺胺类药治疗后发热、咳嗽以及皮疹症状较前好转,出院随诊发热、皮疹已消失.结论 毛细胞白血病出现不明原因感染征象,且应用广谱抗生素、抗真菌药（不含棘白菌素类药）无效时,考虑肺孢子菌肺炎等机会性感染可能,毛细胞白血病伴有CD4＋细胞数≤200 /mm3或存在免疫功能受抑为诱发肺孢子菌感染的高危险因素；另外毛细胞白血病若出现皮肤散在斑疹,特别是同时合并肺孢子菌肺炎时,应考虑Sweet综合征可能性.     

儿童肾母细胞瘤合并肺转移的临床特点和治疗

目的:探讨儿童肾母细胞瘤合并肺转移的临床特征和治疗经验。方法:回顾性分析北京儿童医院血液病中心收治的10例儿童肾母细胞瘤合并肺转移的临床特征和治疗经验。结果:本组10例儿童肾母细胞瘤合并肺转移患者中4岁以下3例,中位年龄5岁半,最小年龄3月,最大11岁;病程最短10天,最长1例为化疗7年肺转移复发。临床表现:腹部肿物8例(80%),血尿2例(20%),咳嗽、咳痰表现6例(60%),发热2例(20%)。影像学检查:所有患儿确诊肾母细胞瘤后行瘤灶评估检查,B超左肾受累6例(60%),右肾受累2例(20%),双肾受累2例(20%);胸部CT提示肺部结节影,2例患儿单侧肺受累;8例患儿为双肺受累有结节影,其中2例患儿有胸腔积液。临床分期:3例患儿为复发,首次确诊肾母分期I期1例(10%),Ⅱ期2例(20%),余7例患儿为首次确诊,Ⅳ期5例(50%),V期2例(20%)。病例分型:胚芽型5例,间叶型2例,上皮型1例,混合型2例。治疗:本组10例患儿全部经手术切除瘤灶,诊断明确根据COG-I方案化疗,10例患者中1例患儿化疗2疗程失访。7例患儿化疗2疗程评估有效,1例患儿化疗6月病情进展放弃治疗。1例患儿化疗评估瘤灶进展换方案。2例患儿放疗。结论:儿童肾母细胞瘤合并肺转移多属晚期,发病年龄大。表现为腹部肿物,血尿,咳嗽、咳痰表现,病理分型为预后良好型,手术、化疗治疗有一定效果。     

急性白血病化疗后合并结核感染临床分析

目的 探讨急性白血病化疗后合并结核感染的临床特点、诊断、治疗和转归.方法 回顾性分析了我院198例急性白血病患者中合并结核感染的4例患者的临床资料,并进行相关文献复习.结果 198例急性白血病患者中有4例(2.02%)合并结核感染,其中急性髓系白血病及急性淋巴细胞白血病各2例,均存在应用化疗药物及化疗后骨髓抑制期白细胞减少等易感因素,临床表现为发热、咳嗽等,给予抗结核治疗后,3例病情比较稳定,目前随访均处于完全缓解中,1例因白血病复发死亡.结论 急性白血病化疗后易合并结核感染,发病率高于正常人群,其临床特点不典型,抗结核治疗后疗效确切,不影响患者的长期生存.     

儿童急性早幼粒细胞白血病合并分化综合征及颅内出血一例并文献复习

目的:提高对儿童急性早幼粒细胞白血病（APL）合并分化综合征（DS）及颅内出血诊治的认识。方法:总结2020年10月12日深圳市儿童医院收治的1例APL合并DS及颅内出血患儿诊治经过，并复习相关文献。结果:患儿，男性，12岁，应用维甲酸及三氧化二砷过程中出现DS并颅内出血，暂停用维甲酸，采用糖皮质激素防治DS，联合化疗及对症治疗后病情好转。结论:APL合并DS及颅内出血病情凶险，建议暂停维甲酸，应用激素并联合化疗、对症治疗可改善预后。     

AB型胸腺瘤伴多发皮下转移1例并文献复习

目的：探讨胸腺瘤的临床、病理、诊疗方法及预后。方法：总结1例AB型胸腺瘤伴多发胸腹壁皮下转移患者的临床资料及诊疗过程,并复习国内外文献。结果：患者男性,25岁,因侵袭性胸腺瘤术后复发并上腔静脉综合征急诊入院,肿瘤生长速度快、病情危急,遂予超分割放射治疗,纵隔占位照射DT 30Gy/20fx/12d,治疗过程中,患者胸腹壁无明显诱因下出现多发性结节灶,质硬,活动尚可,活检病理提示低度恶性肿瘤,考虑为＂胸腺瘤＂术后累及胸腹壁。予2周期TP方案静脉化疗后皮下转移灶逐渐增大、增多。行外周血基因检测,结果示外周血MGMT甲基化阳性,调整治疗方案予干扰素,300万单位,肌肉注射,每周3次;同时口服司莫司汀胶囊,50mg/（w.6w）,治疗过程中查体、复查胸部CT提示皮下转移灶逐渐变小,甚至消失,患者病情控制。结论：胸腺瘤依据病理学检查确诊,其治疗以手术为主,术后复发或病灶呈侵袭性生长常规行放射治疗,对具有特殊临床表现、难治性病例,可考虑基因指导下个体化治疗方式。     

乳腺癌合并肺孤立性结节外科治疗的临床分析

为了探讨外科治疗在乳腺癌合并肺孤立性结节诊断及治疗中的作用,对13例乳腺癌根治术同期行肺孤立性结节手术切除的临床资料进行回顾性分析。结果:手术治疗的13例患者中,肺孤立性病灶的病理结果6例为原发性肺癌,5例为乳腺癌肺转移,2例为良性病变;手术方式:1998年以前患者采用小切口开胸手术(4例),之后的患者采用胸腔镜辅助小切口手术(9例)。术后并发症为皮下气肿和支气管胸膜瘘,无手术死亡。初步研究结果提示,乳腺癌合并的肺孤立性结节并不都是肺转移瘤,乳腺癌合并肺孤立性结节应该尽可能取得病理诊断,得到正确的治疗。     

成年急性白血病化疗前后合并肝功异常的临床分析

本文分析了55例急性白血病合并肝功异常病人化疗后肝功变化及疾病转归情况,认为尽管肝功异常的原因、发生时间及程度不同,化疗并不会影响疾病的总体预后。提示临床医生不必对白血病合并肝功异常病人的化疗产生过多疑虑。     

Hepatosplenic candidiasis in children with acute leukemia

Three children with acute lymphoblastic leukemia developed disseminated fungal disease predominantly involving the liver and spleen. The three patients were undergoing induction chemotherapy and had neutropenia when they presented prolonged fever not responsive to antibiotics. Once neutropenia was recovered, hepatosplenomegaly leukocytosis, elevated serum alkaline phosphatase, and hypoechoic areas in the spleen and liver ultrasound were observed. All fungal blood cultures were negative, with the diagnosis being confirmed by histologic study. One of the patients died without achieving control of the candidiasis. The other two patients received prolonged antifungal treatment concurrently with chemotherapy and both are alive, one of them cured and in complete remission. The increasing frequency of this infection in recent years and the importance of a prompt and prolonged administration of antifungal therapy to obtain the cure are discussed.     

Successful unrelated cord blood transplantation in Philadelphia chromosome positive acute lymphoblastic leukemia during pulmonary aspergillosis treated by anti-fungal therapy, granulocyte colony-stimulating factor-mobilized granulocytes and surgical resection: case report.

A 3-year-old girl with Philadelphia chromosome positive acute lymphoblastic leukemia developed pulmonary aspergillosis during severe neutropenia by re-induction therapy. She was treated by intravenous fluconazole, oral itraconazole with plasma level monitoring and surgical resection of the focus for 3 months after clinical diagnosis of fungal infection was made. Once she had recovered from surgery we attempted to induce remission with anti-fungal treatment. She developed fever and neutropenia and appeared unlikely to remit with conventional chemotherapy. Unrelated one-antigen-mismatched cord blood (CB) transplantation was performed 2 months after the induction therapy. Her pulmonary aspergillosis was reactivated during subsequent conditioning. Anti-fungal drugs were switched to amphotericin B and granulocyte colony-stimulating factor-mobilized granulocyte concentrates were transfused. She obtained engraftment and has maintained complete hematological and molecular remission without signs of aspergillus infection for 13 months so far after transplantation. Even very high-risk transplantation in pediatric patients could be successfully supported by carefully designed intense comprehensive medical care.     

Chronic disseminated candidiasis in patients with acute leukemia: emphasis on diagnostic definition and treatment

BACKGROUND: Chronic disseminated candidiasis (CDC) is a form of invasive fungal infection that occurs most commonly in patients with acute leukemia treated with chemotherapy. Recent studies have provided evidence for diagnostic alternatives to invasive procedures and more therapeutic options for the management of this complication. In order to put diagnostic criteria and methodological approach to the disease into the perspective of developing strategies for therapy, all relevant studies published in the English literature over the last 30 years were examined. MATERIALS AND METHODS: The English-language articles located through MEDLINE (1966 to present) and from selected bibliographies. RESULTS: There is increased recognition of CDC as complication of treatment with chemotherapy in patients with acute leukemia. Liver biopsy may not always be revealing or feasible to perform in some patients. Among the imaging modalities, magnetic resonance imaging has obtained preeminence as a non-invasive tool for the diagnosis of hepatosplenic fungal infections. Administration of amphotericin B (Amp B) in relatively large cumulative doses is needed to ensure appropriate control of the infection and prevention of future relapse. Patients intolerant of, or refractory to conventional Amp B have been successfully salvaged using fluconazole or lipid formulations of Amp B. A constellation of clinical, laboratory and radiologic parameters should be used to determine response and efficacy of therapy. There is sufficient evidence to support the safety and feasibility of continuing chemotherapy for acute leukemia in conjunction with antifungal treatment in patients diagnosed with CDC. CONCLUSION: The development of CDC in patients with acute leukemia does not preclude further chemotherapy or constitute contraindication for bone marrow transplantation. Knowledge of the course and pattern of evolution of the disease and adopting aggressive therapeutic approach will likely reduce the morbidity and mortality from this complication.     

Invasive Aspergillosis in Neutropenic Patients with Hematological Disorders

Between 1983-1988, 72 patients with acute leukemia and 4 with aplastic anemia were treated in the Hematology Unit of The Chaim Sheba Medical Center. Ten patients with acute leukemia developed invasive pulmonary aspergillosis and 2 with aplastic anemia developed invasive aspergillosis of the nose and paranasal sinuses. These infections were diagnosed during a period of profound neutropenia while these patients were receiving broad spectrum antibiotics. The diagnosis of pulmonary aspergillosis was based on positive sputum cultures in 4 cases and on the appearance of typical clinical and radiologic features in six. In 2 culture-positive and in one culture-negative patient, the diagnosis was confirmed at autopsy. Thus, the diagnosis was definitive in 5 patients and probable in the remaining five patients. The 5 patients who achieved remission responded to antifungal treatment and recovered, while of the 5 who eventually died from the fungal infection, 4 did not achieve remission, and one died while in complete remission. In the 2 patients with aplastic anemia, aspergillosis was detected in cultures from necrotic nasal tissue. Both patients remained neutropenic, failed to respond to antifungal treatment and died within a short time after diagnosis. From this experience it appears that invasive aspergillosis in neutropenic patients is potentially curable if treated early by amphotericin B, provided that the neutrophil count recovers.     

Diagnosis and treatment of fungal infections in patients with hematologic malignancies

A diagnosis of deep-seated mycosis was made in 54 patients with hematologic malignancies, severe neutropenia and fever, based on a set of clinical and laboratory criteria. Standardized antifungal treatment was started in 31 patients who seven days after onset of fever had not responded to antibiotics; the fungal infection was cured in 13, all of whom had a simultaneous remission of neutropenia, whereas the other 18 who did not respond to antifungal treatment, all had a falling or static neutrophil count. None of the 23 patients who were given no or inadequate antifungal treatment survived regardless of the neutrophil count and/or phase of the hematologic disease. We discuss the suitability of utilizing empirical criteria for a diagnosis of disseminated fungal infection as a basis for starting antifungal therapy in this type of patient.     

Rapid improvement of osseous sarcoidosis after the treatment of pulmonary aspergillosis by itraconazole

Osseous sarcoidosis is relatively uncommon, and treatment with corticosteroids is not always effective. Moreover, patients with an advanced stage of pulmonary sarcoidosis are sometimes infected with aspergillus in the cavities of the pulmonary lesions, and long-term use of corticosteroids should be prohibited to prevent the development of fatal invasive pulmonary aspergillosis. Here, we described a unique case of osseous sarcoidosis with pulmonary aspergillosis, showing a rapid improvement of the osseous symptoms just after the administration of the antifungal agent, itraconazole. Itraconazole is likely to become a candidate among new therapeutic agents for osseous sarcoidosis.     

Fatal hemophagocytic syndrome in a patient with panniculitis-like T-cell lymphoma and no clinical evidence of disease

Panniculitis-like T-cell lymphoma is an uncommon type of extranodal T-cell lymphoma which presents clinically with subcutaneous nodules. The clinical course can either be indolent or rapidly progressive, often complicated by hemophagocytic syndrome. We report a patient with primary subcutaneous disease and initial complete response to combination chemotherapy. The patient experienced an early relapse which responded to salvage chemotherapy. However, she died shortly thereafter with hemophagocytic syndrome, polymicrobial sepsis and systemic fungal infection. At autopsy there was no evidence of lymphoma in the bone marrow or other organs. We emphasize that a fatal hemophagocytic syndrome can occur despite minimal or even without evidence: of clinically active lymphoma as demonstrated by autopsy in this case.     

Amphotericin B lipid complex for the treatment of patients with acute leukemia and hepatosplenic candidiasis

Hepatosplenic candidiasis (HSC) is an emerging complication of the treatment of patients with acute leukemia. Treatment of this infection can be very difficult and data on the duration of antifungal therapy are not available. We evaluated the efficacy of amphotericin B lipid complex (ABLC) for the treatment of five patients with acute leukemia and HSC. The dose of the administered ABLC ranged between 5 and 11 mg/kg per day and the median duration of therapy was 4.3 months. Four patients had complete response to the above treatment with resolution of fever and improvement in the radiologic findings. One patient refused to continue treatment and subsequently died with relapsed leukemia and disseminated Candida infection. Preliminary data suggest that ABLC is a well-tolerated and effective treatment for HSC and should be considered for phase II trials as front line treatment for this type of deep seated fungal infections.     

Cost-effectiveness analysis of antifungal treatment for patients on chemotherapy

Invasive fungal infections are fatal complications for patients on chemotherapy, and antifungal prophylactic treatment has been commonly recommended. Because its clinical and economic impact is not well known, we evaluated cost-effectiveness of anti-fungal treatment for patients who were neutropoenic as a result of chemotherapy. We constructed a hypothetical cohort of 40-year-old patients with acute myelogenic leukemia to evaluate years of life survived (YLS), costs (US$), and incremental cost-effectiveness ratio (US$/YLS). The following treatment strategies for fungal infections were compared: (1) prophylactic fluconazole strategy: oral fluconazole administration concurrently with chemotherapy; (2) empirical amphotericin B strategy: empirical intravenous amphotericin B administration at the point where fever is detected; and (3) no prophylaxis strategy: intravenous micafangin administration at the point where fungal infections is diagnosed. Baseline analyses showed that prophylactic fluconazole strategy involved higher costs but also longer YLSs (25,900 US$ and 24.08 YLS). The incremental cost-effectiveness ratio of prophylactic fluconazole strategy was 625 US$/YLS compared to no prophylaxis strategy, and 652 US$/YLS compared to empirical amphotericin B strategy. Baseline result was found to be robust through sensitivity analyses. Our study showed that concurrent administration of oral fluconazole during induction chemotherapy appears to ensure clinical benefits together with acceptable cost-effectiveness.     

Posaconazole prophylaxis in patients with acute myelogenous leukaemia--results from an observational study

Patients with acute myelogenous leukaemia (AML) and neutropenia after chemotherapy are at high risk for life-threatening invasive fungal disease (IFD), in particular, invasive aspergillosis (IA). The aim of the study was to evaluate data on characteristics, risk factors, complications and additional antifungal treatment of patients with AML receiving posaconazole prophylaxis (PP) after chemotherapy in an actual clinical setting. A retrospective single-centre observational study on 40 patients with AML, median age 66 years, was conducted. PP 200 mg three times daily was given routinely. After 76 cycles of remission induction chemotherapy followed by PP, median duration of 31 days (range 6-61 days), no fatal case occurred. The majority of patients had at least one additional risk factor for IFD and during 32 cycles (42.1%), three risk factors were present. During 40 therapy cycles (52.6%), fever of unknown origin occurred. Pneumonia was diagnosed after 23 cycles (30.3%), thereof one case of proven IA (1.3%). PP was interrupted in 25 cycles (32.9%) and was followed by systemic antifungal therapy with different agents, with a median duration 15 days (range: 6-32 days). PP appears to be an effective and well-tolerated protection against IFD for AML patients under natural clinical conditions.