Invasive Fungal Infections in Patients With Chronic Lymphoproliferative Disorders in the Era of Target Drugs

Abstract

This review summarizes the more recent evidence about epidemiology and risk factors for invasive fungal infections (IFI) in patients affected by Chronic Lymphocytic Leukemia (CLL), indolent Non Hodgkin Lymphoma (iNHL) and Multiple Myeloma (MM).Despite advances in the prognosis and treatment of hematological malignancies in recent years, susceptibility to infection remains a significant challenge to patient care. A large amount of data regarding patients with acute leukemia has been published while little information is available on the incidence of IFI in chronic lymphoproliferative disorders (CLD).New drugs are now available for treatment of lymphoproliferative disorders which may cause suppression of humoral immunity, cellular immunity, and deficiency of white blood cells, increasing the risk for infections which remain the leading cause of mortality in these patients.

Cerebral Invasive Aspergillosis in a Case of Chronic Lymphocytic Leukemia with Bruton Tyrosine Kinase Inhibitor

“…This will mandate either dose reduction or the interruption of CLL therapy, which will convey a higher risk of early CLL relapse if BTK is stopped in an incomplete remission state. One limitation to our report is the initial combination with obinutuzumab, as this agent contributes to more lymphodepletion and the suppression of humeral and cellular immunity [ 20 ]. The key learning points from this case are (1) to maintain a high index of suspicion when treating CLL patients with BTK inhibitors as single agents or in combination with anti-CD20 monoclonal antibodies, and (2) to request mycological studies when a tissue biopsy is performed, especially if the site of infection carries a high risk of complications, as the brain does.…”

Small-Molecule Protein Kinases Inhibitors and the Risk of Fungal Infections

“…There were a similar number of cases reported with ibrutinib monotherapy as combination therapy [19]. Steroid therapy, allogeneic stem cell transplantation, three or greater prior treatments, prolonged neutropenia, diabetes, and liver disease all represented additional risk factors for fungal infections [22][23][24]. Patients with Pneumocystis jirovecii pneumonia demonstrated normal CD4+ T cell counts and immunoglobulin levels, suggesting that a high level of clinical suspicion may be required to diagnose infections in these patients [25].…”

A Prospective Multicenter Cohort Surveillance Study of Invasive Aspergillosis in Patients with Hematologic Malignancies in Greece: Impact of the Revised EORTC/MSGERC 2020 Criteria

“…Over the last decades, advances in the treatment of hematologic malignancies have been paralleled by a growing prevalence and changing epidemiology of invasive aspergillosis (IA) in hematology patients [ 1 , 2 , 3 ]. The incidence rates of IA among this high-risk population are very much dependent on local epidemiology as they may vary according to patient characteristics and care practices [ 2 , 4 , 5 ], while they are even subject to seasonal variations of climate variables and local conditions [ 6 ].…”