泊沙康唑初级预防急性髓系白血病诱导化疗后发生侵袭性真菌病的临床评估

目的观察泊沙康唑口服悬液初级预防急性髓系白血病(AML)患者诱导化疗后发生侵袭性真菌病(IFD)的疗效及毒副反应。方法收集2016年5月至2018年5月宁波市鄞州人民医院血液科收治的所有符合入选和排除标准的初诊AML患者206例(除外急性早幼粒细胞白血病、入院后接受静脉抗真菌或诱导化疗前1个月发生IFD、合并重要脏器功能不全、年龄>65岁),其中诱导化疗期间使用泊沙康唑口服悬液进行初级预防IFD的患者47例(泊沙康唑组),使用伏立康唑片进行初级预防IFD的患者61例(伏立康唑组),未进行初级预防IFD的患者98例(对照组)。对各组临床资料进行回顾性分析,比较3组诱导化疗期间IFD的发生率及泊沙康唑口服悬液、伏立康唑片的药物安全性。结果(1)泊沙康唑组出现5例(10.6%)IFD,均为拟诊病例;伏立康唑组出现11例(18.0%)IFD,其中拟诊7例,临床诊断3例,确诊1例;对照组出现35例(35.7%)IFD,其中拟诊19例,临床诊断11例,确诊5例。泊沙康唑组和伏立康唑组IFD的发生率均明显低于对照组(P值均<0.05)。泊沙康唑组IFD的发生率低于伏立康唑组,但差异无统计学意义(P>0.05)。(2)泊沙康唑组不良事件发生率明显低于伏立康唑组[12.8%(6/47)比32.8%(20/61),P<0.05]。结论(1)AML诱导化疗期间使用泊沙康唑口服悬液或伏立康唑片进行初级预防,可以明显减少IFD的发生率;(2)AML诱导化疗期间使用泊沙康唑口服悬液和伏立康唑片进行初级预防IFD的疗效相当,但泊沙康唑口服悬液安全性更好。     

急性白血病化疗后继发肺部真菌感染一例

<正>病例资料患者女性,42岁,因咽痛、牙龈肿痛、发热20余天于2017年5月13日入院。既往否认肝炎、结核及手术史。查体:体温37.8℃,贫血貌,齿龈增生,头颈部浅表淋巴结可触及肿大。咽部略充血、红肿,双肺、心脏、腹部查体未见异常。     

Epidural abscess in the spine extended from pulmonary zygomycosis during consolidation chemotherapy for acute lymphoblastic leukemia

A 37-year-old woman with acute lymphoblastic leukemia developed fever and pneumonia during persistent neutropenia after consolidation chemotherapy. Pneumonia was rapidly followed by the formation of abscess in adjacent subcutaneous tissues, muscles and bones. She subsequently developed sudden onset of paraplegia and loss of all sensation below Th4. Epidural abscess was detected by MRI. Emergency drainage was performed, but the patient died 4 days after the operation. Rhizopus oryzae grew from culture of the epidural abscess. Since the incidence of zygomycosis appears to have increased over the recent years, clinicians should be aware of the possibility of zygomycosis in case of any infection that is resistant to antibiotics.     

Treatment with voriconazole for invasive fungal infection during chemotherapy for leukemia: doses and plasma concentration of voriconazole in children

We report on 4 children with invasive fungal infections complicated with leukemia who responded to voriconazole (VRCZ). In 3 children aged 1-6 years, the plasma VRCZ concentration was low and clinically ineffective after its administration at a dose of 4 mg/kg. Good plasma concentrations could be attained by increasing the dose to 5.3-12 mg/kg, and clinical effects were observed. In the other 13-year-old male, an adequate plasma concentration could be obtained after VRCZ administration at a dose of 4 mg/kg. Concerning adverse effects, transient visual abnormality developed in only 1 child. VRCZ may be effective and safe not only in adults but also in children with invasive fungal infection during chemotherapy for leukemia. Though the dose in adults is 3-4 mg/kg, the dose/weight in children should be higher because of the greater clearance. Since there are also individual differences in drug metabolism, the dose in children should be individually adjusted based on the plasma concentration.     

First case of disseminatedMycobacterium avium infection following chemotherapy for childhood acute myeloid leukemia

Summary A 14-year-old girl of Indian origin with acute myeloid leukemia (AML) is presented, who was diagnosed at the age of twelve. Antileukemic chemotherapy had to be discontinued after 6 weeks because of persistent high fever and the emergence of liver and spleen abscesses. Serologic and biopsy findings were consistent with disseminated candidiasis; however, a liver biopsy also revealed granulomatous lesions with caseous degeneration. No acid-fast bacilli could be detected. Upon antifungal treatment the patient's condition improved, but fever spells and high inflammatory blood parameters persisted. One year after the diagnosis of AML was established,Mycobacterium avium was cultured from bone marrow aspirates. The patient's cellular immunity was severely compromised at that time as reflected by the marked depression of T-lymphocyte counts, in particular of CD4-positive cells. HIV and other lymphotropic virus infections were subsequently excluded. After 5 months of specific treatment the patient recovered from mycobacterial infection and remains in first remission of AML. Opportunistic infections have rarely been diagnosed in oncologic patients to date, while data on T-cell function in AML is sparse. Fever of unknown origin should prompt the search for infectious agents unusual to date in this patient group.

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Erster Fall einer disseminiertenMycobacterium avium-Infektion nach Chemotherapie wegen akuter myeloischer Leukämie im Kindesalter

Zusammenfassung Der Fall eines 14jährigen Mädchens indischen Ursprungs wird dargestellt, bei dem im Alter von 12 Jahren eine akute myeloische Leukämie (AML) diagnostiziert wurde. Die Chemotherapie mußte nach sechs Wochen wegen anhaltend hohen Fiebers und des Auftretens von Leber- und Milzabszessen abgebrochen werden. Serologische wie histologische Befunde sprachen für eine disseminierte Candida-Infektion; es fanden sich aber auch Granulome mit zentraler Verkäsung in der Leberbiopsie. Säurefeste Stäbchen konnten nicht nachgewiesen werden. Der Zustand der Patientin besserte sich unter fungistatischer Therapie, jedoch persistierten Fieberschübe und hohe Serumentzündungsparameter. Erst ein Jahr nach Manifestation der AML konnte eine Infektion mitMycobacterium avium aus Knochenmarksaspiraten diagnostiziert werden. Bei der Untersuchung der zellulären Immunität fand sich ein ausgeprägter Mangel an T-Lymphozyten und speziell an CD4-positiven Zellen. Eine Infektion mit HIV und anderen lymphotropen Viren konnte ausgeschlossen werden. Nach fünf Monaten spezifischer Therapie erholte sich die Patientin, sie ist in anhaltender Remission der AML. Opportunistische Infektionen wurden bisher bei onkologischen Patienten selten diagnostiziert; andererseits bietet die Literatur wenig Information über T-Zellfunktion bei AML. Bei Fieber unklarer Ursache müssen auch bislang selten diagnostizierte Infektionen in dieser Patientengruppe in Erwägung gezogen werden.

     

Timed sequential chemotherapy for advanced acute myeloid leukemia

Timed sequential chemotherapy (TSC) combining mitoxantrone on days 1–3, etoposide on days 8–10 and cytarabine on days 1–3 and 8–10, was administered to 240 patients with advanced acute myelogenous leukemia (AML). Sixty one percent of patients, with a 95% confidence interval (CI) ranging from 54 to 67%, achieved complete remission (CR), including 47% (CI: 38–55%) of refractory patients and 78% (CI: 70–86%) of late first relapse patients (p < 0.0001). Thirty percent of patients did not respond to therapy and 9% died from toxicity. Median duration of neutropenia was 32 days and of thrombocytopenia 29 days. Severe non hematologic toxicity included sepsis in 45% of patients and mucositis in 27%. Post-remission therapy varied but included maintenance chemotherapy in most patients, a second course of TSC in 27, autologous stem cell transplantation in 17 and allogeneic transplantation in 20. Median survival of patients who were not transplanted was 7 months with 13% (CI: 7–19%) survival at 5 years. Median disease-free survival (DFS) was 9 months with 13% (CI: 6–20%) DFS at 5 years. Previous refractoriness was the main factor associated with poor prognosis for achieving CR, DFS and survival in a multivariate analysis. There was no difference in DFS between patients receiving the different modalities of intensive post-remission therapy. These results confirm initial reports on TSC and show that some patients with first relapse off therapy can enjoy prolonged DFS using chemotherapy only.     

Timed sequential chemotherapy for advanced acute myeloid leukemia

Timed sequential chemotherapy (TSC) combining mitoxantrone on days 1–3, etoposide on days 8–10 and cytarabine on days 1–3 and 8–10, was administered to 240 patients with advanced acute myelogenous leukemia (AML). Sixty one percent of patients, with a 95% confidence interval (CI) ranging from 54 to 67%, achieved complete remission (CR), including 47% (CI: 38–55%) of refractory patients and 78% (CI: 70–86%) of late first relapse patients (p < 0.0001). Thirty percent of patients did not respond to therapy and 9% died from toxicity. Median duration of neutropenia was 32 days and of thrombocytopenia 29 days. Severe non hematologic toxicity included sepsis in 45% of patients and mucositis in 27%. Post-remission therapy varied but included maintenance chemotherapy in most patients, a second course of TSC in 27, autologous stem cell transplantation in 17 and allogeneic transplantation in 20. Median survival of patients who were not transplanted was 7 months with 13% (CI: 7–19%) survival at 5 years. Median disease-free survival (DFS) was 9 months with 13% (CI: 6–20%) DFS at 5 years. Previous refractoriness was the main factor associated with poor prognosis for achieving CR, DFS and survival in a multivariate analysis. There was no difference in DFS between patients receiving the different modalities of intensive post-remission therapy. These results confirm initial reports on TSC and show that some patients with first relapse off therapy can enjoy prolonged DFS using chemotherapy only.     

Impact of invasive fungal disease on the chemotherapy schedule and event-free survival in acute leukemia patients who survived fungal disease: a case-control study

Patients with acute leukemia who initially survive invasive fungal disease must receive chemotherapy or go on to transplant. Many centers change subsequent chemotherapy to decrease the risk of fungal reactivation. This case-control study compared acute leukemia patients (n=28) who developed a proven or probable fungal disease and survived four weeks later, to patients who did not (n=78), and assessed the impact of fungal disease on the chemotherapy regimens, and overall and event-free survival. Chemotherapy changes (i.e. delays, dose-reduction) were more frequent in the fungal (68%) than in the control group (24%) (P<0.001). Although there was no difference in overall and event-free survival between groups, they were both lower for proven fungal disease cases when compared to controls (HR 2.4, 95% CI 1.1-1.5, and HR 2.9, 95% CI 1.4-5.6, respectively). Patients with invasive fungal disease, even though they initially survive, undergo significant changes to their chemotherapy therapy. This impacts on the survival of patients with proven fungal disease.     

初治急性白血病诱导化疗期间侵袭性真菌感染临床分析

目的 分析初治急性白血病惠者的侵袭性真菌感染发生率并探讨其危险因素.方法 回顾性分析2007年1月至2008年6月北京大学人民医院血液科一个病房连续收治的80例初治急性白血病患者的临床资料.结果 急性白血病诱导化疗期间真菌感染发生率为13.8%.发生真菌感染的危险因素有老年、高白细胞以及使用广谱抗生素时间较长.结论 初治急性白血病诱导化疗期间的真菌感染发生率较高,在高危患者中有必要进行真菌感染预防.     

Benign thymic hyperplasia after chemotherapy for acute myeloid leukemia

Thymic hyperplasia can occur after cytotoxic therapy for various malignancies. The possible cause could be rebound enlargement after initial atrophy caused by these drugs. During the treatment of hematological malignancies this could be a cause of great concern. We report here a case of thymic hyperplasia after chemotherapy for acute myeloid leukemia. Awareness of this unusual side-effect may prevent needless investigation and therapy.     

Massive hepatic infarction occurred during the myelosuppression after re-induction chemotherapy for acute myeloid leukemia

Since the liver has a duplicate blood supply through the hepatic artery and portal vein, hepatic infarction is considered a rare disease. A 51-year-old male with acute myeloid leukemia and diabetes mellitus developed fulminant hepatic infarction only a few days after administration of FLAGM chemotherapy. Our case was considered to have been caused by the almost complete obstruction of both the hepatic artery and portal vein by thrombi during a short period. Hepatic infarction should be recognized as a complication that may develop after salvage chemotherapy such as FLAGM inducing marked myelosuppression. Hepatic infarction after chemotherapy requires further analysis by evaluating a larger number of cases.     

Successful second allogeneic bone marrow transplantation in a relapsed acute myeloid leukemia patient with fungal liver abscess

Summary Disseminated fungal infection not infrequently complicates the course of allogeneic bone marrow transplantation (allo BMT) in severely immunocompromised patients, and the prognosis of BMT patients who develop systemic fungal infection is very poor. We describe a patient who developed disseminatedCandida albicans infection with liver abscess after the first allo BMT for acute myelogenous leukemia (FAB M2). The infection was successfully eradicated by the administration of miconazole and amphotericin B. However, 1 year after the first allo BMT, the patient suffered a relapse of acute myelogenous leukemia with fungal liver abscess. A second allo BMT, accelerating granulocyte recovery by recombinant human granulocyte colony-stimulating factor (rhG-CSF), was successfully performed and the fungal liver abscess resolved with a combination therapy of fluconazole and amphotericin B. The patient is alive and free of both leukemia and fungal disease more than 37 months after the first allo BMT and 25 months after the second allo BMT.     

国产伏立康唑治疗急性白血病合并侵袭性真菌感染的疗效观察

目的 观察国产伏立康唑治疗急性白血病合并侵袭性真菌感染(IFI)的临床疗效和安全性.方法 回顾性分析30例急性白血病合并IFI住院患者使用国产伏立康唑治疗的效果.结果 国产伏立康唑治疗30例IFI患者的总有效率为53.3%(16/30),5例患者出现不良反应,经处理后全部好转.结论 国产伏立康唑是治疗急性白血病合并IFI患者的有效药物,不良反应少,安全性高.     

D-index dose not predict the development of pulmonary infection in acute myeloid leukemia patients undergoing consolidation chemotherapy with high-dose cytarabine

The D-index is calculated as the area over the neutrophil curve during neutropenia. We investigated the impact of the D-index on pulmonary infection in 33 acute myeloid leukemia patients undergoing consolidation chemotherapy with high-dose cytarabine. There was no difference in the D-index between chemotherapies with and without pulmonary infection. The cumulative D-index (c-D-index) until the development of infection exceeded 4000 in four of five patients with pulmonary infection. Although there was no difference in the total D-index throughout the overall consolidation chemotherapy, the total D-index from induction to consolidation and the D-index at induction chemotherapy were higher in patients with pulmonary infection during consolidation than in those without it (P = 0.014 and 0.019, respectively). Our results showed that the cumulative effect of neutropenia might determine the risk of pulmonary infection in consolidation chemotherapy. We are planning a clinical trial of c-D-index-guided preemptive antifungal therapy.