A Systematic Review to Assess the Relationship between Disseminated Cerebral Aspergillosis, Leukemias and Lymphomas, and Their Respective Therapeutics

Abstract

Disseminated disease following invasive pulmonary aspergillosis (IPA) remains a significant contributor to mortality amongst patients with hematologic malignancies (HMs). At the highest risk of mortality are those with disseminated disease to the central nervous system, known as cerebral aspergillosis (CA). However, little is known about the risk factors contributing to disease amongst HM patients. A systematic review using PRISMA guidelines was undertaken to define HM patient subgroups, preventative measures, therapeutic interventions, and outcomes of patients with disseminated CA following IPA. The review resulted in the identification of 761 records, of which 596 articles were screened, with the final inclusion of 47 studies and 76 total patients. From included articles, the proportion of CA was assessed amongst HM patient subgroups. Further, pre-and post-infection characteristics, fungal species, and mortality were evaluated for the total population included and HM patient subgroups. Patients with acute myeloid leukemia and acute lymphoid lymphoma, patients receiving corticosteroids as a part of their HM therapeutic regimen, and anti-fungal prophylaxis constitute the top identified patient populations at risk for disseminated CA. Overall, information presented here indicates that measures for the prevention of IPA should be taken in higher-risk HM patient subgroups. Specifically, the type of anti-fungal therapy used should be carefully considered for those patients with IPA and increased risk for cerebral dissemination. Additional reports detailing patient characteristics are needed to define further the risk of developing disseminated CA from IPA in patients with HMs.

Development of a murine model to study the cerebral pathogenesis of Aspergillus fumigatus

“…Studying disseminated aspergillosis in the context of corticosteroid use is clinically relevant, given that 25%–50% of patients with CA are being treated with corticosteroids for hematological malignancies, graft versus host disease, or transplant therapy ( 17 , 18 ). However, we found that corticosteroid-treated mice were highly susceptible to intravenous challenge with A. fumigatus but interexperimental variability made this model untenable to evaluate the pathogenesis of CA.…”

Neuroimmune Responses in a New Experimental Animal Model of Cerebral Aspergillosis

“…In a recent systematic review, we identified acute myeloid leukemia (AML) as the primary hematologic malignancy associated with CA disseminating from IPA ( 27 ). The induction chemotherapy often employed in AML is a “7 + 3” regimen with the chemotherapeutic drugs cytarabine and daunorubicin (both drugs administered for the first 3 days, with cytarabine alone given for an additional 4 days) ( 28 ).…”