Prophylaxis of invasive aspergillosis with voriconazole or caspofungin during building work in patients with acute leukemia

Background

Invasive aspergillosis is a common life-threatening infection in patients with acute leukemia. The presence of building work near to hospital wards in which these patients are cared for is an important risk factor for the development of invasive aspergillosis. This study assessed the impact of voriconazole or caspofungin prophylaxis in patients undergoing induction chemotherapy for acute leukemia in a hematology unit exposed to building work.

Design and Methods

This retrospective cohort study was carried out between June 2003 and January 2006 during which building work exposed patients to a persistently increased risk of invasive aspergillosis. This study compared the cumulative incidence of invasive aspergillosis in patients who did or did not receive primary antifungal prophylaxis. The diagnosis of invasive aspergillosis was based on the European Organization for Research and Treatment of Cancer/Mycosis Study Group criteria.

Results

Two-hundred and fifty-seven patients (213 with acute myeloid leukemia, 44 with acute lymphocytic leukemia) were included. The mean age of the patients was 54 years and the mean duration of their neutropenia was 21 days. Eighty-eight received antifungal prophylaxis, most with voriconazole (n=74). The characteristics of the patients who did or did not receive prophylaxis were similar except that pulmonary antecedents (chronic bronchopulmonary disorders or active tobacco use) were more frequent in the prophylaxis group. Invasive aspergillosis was diagnosed in 21 patients (12%) in the non-prophylaxis group and four (4.5%) in the prophylaxis group (P=0.04). Pulmonary antecedents, neutropenia at diagnosis and acute myeloid leukemia with high-risk cytogenetics were positively correlated with invasive aspergillosis, whereas primary prophylaxis was negatively correlated. Survival was similar in both groups. No case of zygomycosis was observed. The 3-month mortality rate was 28% in patients with invasive aspergillosis.

Conclusions

This study suggests that antifungal prophylaxis with voriconazole could be useful in acute leukemia patients undergoing first remission-induction chemotherapy in settings in which there is a high-risk of invasive aspergillosis.     

Real‐time PCR on the first galactomannan‐positive serum sample for diagnosing invasive aspergillosis in liver transplant recipients

Abstract: Invasive aspergillosis (IA) is a life‐threatening complication of liver transplantation. Detection of circulating galactomannan (GM) in serum samples is a method to improve the microbiological diagnosis in patients at risk for IA. However, the assay is hampered by false‐positive results. The search for circulating Aspergillus DNA in the first GM‐positive sample could improve the specificity of the test. Among 484 liver transplant recipients followed in a single center over 4 years, 25 patients had at least 1 GM‐positive serum sample. The threshold of GM positivity was a ratio ≥1. These 25 patients were classified by the clinicians as probable IA (n=11), possible IA (n=2), and no IA (n=12) using the EORTC/MSG criteria with blinding to the polymerase chain reaction (PCR) results. After 1 mL aliquots of the first GM‐positive serum sample were thawed, 2 independent DNA extractions were performed using the MagNA Pure Compact apparatus. Real‐time amplification targeted at Aspergillus fumigatus mitochondrial DNA was performed on 10 μL of the final eluate in duplicate in the 2 independent DNA extractions using a LightCycler instrument. A sample was considered positive when the crossing point was ≤43 cycles in at least 2 out of the 4 replicates. Among the 13 probable or possible IA, 8 patients were PCR positive. The other 12 patients who had no IA were all PCR negative. Our data suggest that a concomitant real‐time PCR performed on the first GM‐positive sample improves the specificity of the first GM‐positive assay result.     

Unusual radiological presentation and rapid fatal progression of invasive pulmonary aspergillosis in an immunocompetent young patient

Invasive aspergillosis occurs very rarely in immunocompetent hosts. We describe a 21-year-old female with no obvious immunosuppression or underlying lung disease, who presented with minimal symptoms and bilateral hilar prominence on chest X-ray. Invasive aspergillosis was diagnosed on an open lung biopsy. She deteriorated in the ensuing 2 weeks and died of a sudden massive haemoptysis. This initial radiological abnormality and the rapid clinical course of the disease in young immunocompetent patients have not been previously reported.     

Chronic systemic aspergillosis in a patient with acute myeloid leukemia

 Systemic aspergillosis is a well-recognized complication of chemotherapy-induced neutropenia. In this report a patient with acute myeloid leukemia is described in whom a chronic aspergillosis with systemic involvement developed after recovery from neutropenia following intensive chemotherapy and allogeneic bone marrow transplantation. The clinical features of a chronic course of systemic aspergillosis suggest a distinct clinical entity comparable to chronic systemic candidiasis. Received: 13 November 1997 / Accepted: 11 February 1998     

Successful treatment with micafungin of invasive pulmonary aspergillosis in acute myeloid leukemia,with renal failure due to amphotericin B therapy

Invasive aspergillosis is an important factor in the morbidity and mortality of patients suffering from hematologic disorders treated with chemotherapy. Treatment with amphotericin B is often limited because of toxicity, particularly nephrotoxicity. We describe a case of invasive pulmonary Aspergillus fumigatus infection in acute myeloid leukemia with renal failure due to amphotericin B therapy, which responded to treatment with a new antifungal agent, micafungin. Micafungin appears to be an effective and safe therapy for Aspergillus infections with renal failure due to amphotericin B.     

Primary hepatic aspergillosis following induction chemotherapy for acute leukemia

Invasive aspergillosis (IA) contributes significantly to the burden of infectious complications in heavily immunosuppressed patients with acute leukemia. The infection is typically acquired via inhalation into the respiratory tract, and the lungs are most commonly involved. However, disseminated disease may occur and reports of isolated extrapulmonary infection suggest the gastrointestinal tract is likely an additional portal of entry for this organism. We describe a case of primary hepatic aspergillosis in a patient with acute myelogenous leukemia. The patient did not respond to medical therapy with antifungals and ultimately required surgical exploration and drainage. IA should be considered in an immunosuppressed patient with hepatic abscesses and may require a combined surgical and medical approach to therapy.     

Successful treatment of invasive pulmonary aspergillosis in an immunocompetent host

Immunocompromised individuals are susceptible to pulmonary Aspergillus infection, but invasive Aspergillus infection is extremely rare in the presence of normal immunity. A case of invasive pulmonary aspergillosis in an immunocompetent 57-year-old female who was successfully treated with liposomal amphotericin-B is reported here.     

Inflammatory pseudotumor of the lung following invasive aspergillosis in a patient with chronic graft-vs.-host disease

Inflammatory myofibroblastic tumor (IMT) is an uncommon cause of solitary or multifocal lung nodules and can also be rarely found in various other extrapulmonary sites. Although this pseudotumor is benign, it can be locally very aggressive. The pathogenesis of IMT remains unclear; autoimmune or infectious origins have been hypothesized, so far. Here, we report a case of inflammatory pseudotumor of the lung secondary to invasive pulmonary aspergillosis in a patient with chronic graft-vs.-host disease. The 42-year-old patient presented with coughing and hemoptysis as major clinical signs 1 yr after successful HLA-identical stem cell transplantation. Aspergillus fumigatus was cultured from the bronchoscopic lavage, but intensive antifungal treatment could only initially improve the clinical situation. Diagnostic re-evaluation by open-chest biopsy surprisingly revealed an inflammatory pseudotumor responsible for clinical and radiographical deterioration. Both clinical and radiographical signs resolved under long-term steroids and secondary antifungal prophylaxis.     

Atypical invasive aspergillosis in a neutropenic child

Invasive aspergillosis (IA) is an aggressive disease with a high mortality rate requiring a high index of clinical suspicion in susceptible patients. We report an atypical presentation of IA, not previously published. A 2-year-old girl with underlying neuroblastoma developed IA, which manifested as fungal pneumonia associated with an intrabronchial polypoid mass.     

52例侵袭性肺曲霉菌病临床分析

目的分析侵袭性肺曲霉菌病(IPA)的临床特征。方法对52例IPA患者的基础疾病、宿主因素、临床特征、治疗及转归进行回顾性分析。结果原发性IPA共8例,均获治愈;44例继发性IPA患者,治愈35例,死亡9例。恶性肿瘤放化疗、器官移植、慢性阻塞性肺病急性加重者中,继发性IPA的发病率较高,其临床表现主要有发热、咳嗽、咳痰、喘息、呼吸困难、咯血。IPA患者的肺CT改变呈多样性,并呈动态演变。结论原发性IPA一般预后良好,继发性IPA好发于免疫缺陷的患者,临床表现缺乏特异性,肺CT具备一定的特征,结合宿主因素,为早期治疗提供诊断依据,从而改善预后。     

Nosocomial invasive aspergillosis in a heart transplant patient acquired during a break in the HEPA air filtration system

We report a case of nosocomially acquired invasive aspergillosis (IA) in a low-risk heart transplant recipient due to a break in the air conditioning system. A high overload of Aspergillus spores in the intensive care unit room led this patient to acquire IA. Identical environmental and patient isolates allowed our hypothesis to be confirmed and a very precise incubation time to be estimated.     

Therapy-related acute myeloid leukemia after single-agent treatment with fludarabine for chronic lymphocytic leukemia

A 70-year-old man with B-cell chronic lymphocytic leukemia (CLL) received single-agent treatment with the purine analogue fludarabine, which led to complete remission. After 8 years, he presented with pancytopenia. Marrow examination showed acute myeloid leukemia (AML) with trilineage myelodysplasia (MDS). Cytogenetic analysis showed an unbalanced der(1;7)(p10;q10) that resulted effectively in deletion 7q; confirming the diagnosis of therapy-related AML (t-AML). No residual CLL was present. Together with previous reports of secondary cancers after fludarabine treatment and the association of monosomy 7/7q- with another purine analogue azathioprine, results suggest that t-AML might develop after fludarabine therapy.     

Invasive pulmonary aspergillosis in non‐neutropenic patients with and without underlying disease: A single‐centre retrospective analysis of 52 subjects

Background and objective: Invasive pulmonary aspergillosis (IPA) remains a life‐threatening infection in patients with prolonged neutropenia. Few data are available on IPA in non‐neutropenic patients without underlying immunocompromising conditions. Methods: All non‐neutropenic patients managed at the institution for a proven and probable IPA over the last 10 years were reviewed retrospectively, and the difference between non‐neutropenic patients with and without underlying disease was investigated. Results: Among 52 cases of IPA analysed here, 33 were histologically proven; 19 were probable. Forty‐two (80.8%) patients had underlying diseases; 10 (19.2%) patients had no any underlying diseases. There is a significant difference in seasonal distribution among patients with underlying conditions (P = 0.026), but no seasonal difference was found in the other group (P = 0.622). The only significant difference in symptoms between the two groups was fever (P = 0.015). Radiological findings were non‐specific in the two groups. Despite treatment, the overall crude mortality rate among 52 patients was 39%. The overall mortality rate in patients with underlying disease was 45%, while that in patients without underlying conditions was 11%. A Cox multivariate analysis showed that organ failure (hazard ratios: 8.739, 95% CI: 3.770–20.255; P = 0.000) was independently associated with overall mortality. Conclusions: Clinical features of IPA are not well known in non‐neutropenic patients, especially in those without underlying conditions. In this study, organ failure was associated with a lower rate of survival of non‐neutropenic patients with IPA.     

How I investigate acute myeloid leukemia

Acute myeloid leukemia (AML) is a neoplasm of immature myeloid cells and is associated with a wide variety of clinical presentations, morphological features, immunophenotypes, and genetic findings. Recent advances in identification of cytogenetic abnormalities and mutations have provided novel insights into the pathogenesis of AML. Based on the above‐mentioned parameters, the World Health Organization (WHO) classified AML into 25 subtypes, including 2 provisional entities, which differ in prognosis and treatment. In addition, certain mutations are associated with germline predisposition and increase the risk of inherited AML, which warrants family screening. Therefore, precise diagnosis and classification of AML are the most important steps in patient management. Both these steps require incorporation of history, clinical presentation, and laboratory results with studies performed by a pathologist. Pathologist‐initiated studies include morphologic evaluation on the bone marrow aspirate and/or core biopsy, immunophenotyping by flow cytometry and/or immunohistochemistry, cytogenetic analysis by karyotyping and/or fluorescence in situ hybridization, and molecular testing using gene panels and/or next‐generation sequencing. A similar approach is employed during follow‐up of patients after beginning treatment. Here, we describe in detail the various aspects of the workup, including purpose, limitations, and practice guidelines for the different studies. The process of choosing appropriate materials for the different studies is also addressed. We also provide an algorithm for the workup and risk stratification of AML based on guidelines recommended by the WHO, College of American Pathologists, National Comprehensive Cancer Network, American Society of Clinical Oncology, European Society of Medical Oncology, and the European LeukemiaNet.