Invasive Pulmonary Aspergillosis in Acute Leukemia: Current Issues for Pathogenesis, Diagnosis and Treatment

Abstract

Invasive pulmonary aspergillosis (IPA) is a frequently life-threatening fungal infection that complicates acute leukemia patients following conventional chemotherapy and bone marrow transplantation. The mortality rate reaches 50% in leukemic patients during chemotherapy-induced neutropenia and can exceed 90% in bone marrow transplantation patients. Despite advances in antimicrobial therapy and supportive care, IPA remains a major clinical problem in patients with acute leukemia. Current issues for IPA in adults are reviewed.

Double Invasive Fungal Infection and Typhlitis in Children With Acute Lymphoblastic Leukemia

“…The most relevant predisposing factors to the development of invasive aspergillosis in immunocompromised patients are construction work, cytotoxic chemotherapy, prolonged neutropenia, and corticosteroids or other immunosuppressive therapies [4,11,12]. Patients with bronchial asthma are also at high risk for invasive pulmonary aspergillosis due to inhaled or systemic corticosteroid therapy [13][14][15].…”

“…Prolonged or recurrent neutropenic fever, nonproductive cough, pleuritic pain, and later hemoptysis are usually present in the course of invasive pulmonary aspergillosis, reflecting the potential of Aspergillus to invade blood vessels [11,12]. Two patterns of pulmonary hemorrhage may develop: the first is that of hemorrhagic infarction due to vascular invasion; the second pattern is the formation of mycotic aneurysms during recovery from neutropenia, where rupture can cause potentially fatal hemoptysis [11].…”

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“…It is carried by air and overcomes the defensive abilities of upper respiratory tract and penetrates up to distal alveolar spaces. Thereafter, it germinates into angioinvasive filamentous hyphae that produce local tissue damage, hemorrhage, infarction and coagulative necrosis [ 6 , 15 - 17 ].…”

“…Sudden onset of shortness of breath, pleuritic chest pain, hemopthysis, pulmonary infiltrates, and fever un-responsive to broad-spectrum antibiotics constitute the characteristic clinical picture of the disease [ 15 , 16 ]. Early diagnosis of IPA remains difficult mainly because clinical signs and symptoms are not specific, culture and microscopy of lower respiratory tract specimens have low sensitivity, and histopathological examination of infected tissue is not easy due to often-poor condition and underlying coagulation abnormalities of patient [ 15 ]. Chest radiograph findings are not sensitive and specific for IPA, and also it may be normal in up to 10% [ 6 ].…”

“…HRCT scan is the most sensitive radiological method to detect early changes of IPA. "Halo sign" which correlates with hemorrhage and edema surrounding an infarct by thrombosis occurs early in the course of infection and is highly suggestive of IPA in patients with neutropenia and leukemia [ 6 , 15 - 17 ]. Air crescent sign, which is a central necrotic nodule with circumferential air density, develops mainly at the time of BM recovery.…”