Successful treatment of cerebral aspergillosis: case report of a patient with T-cell large granular lymphocytic leukemia (T-LGL)

Abstract

BackgroundInvasive aspergillosis involving patients with neutropenia or severe immunosuppression, such as patients with hematologic malignancies is associated with high mortality. Patients with T-cell large granular lymphocytic leukemia (T-LGL) on the other hand are considered to be less vulnerable for severe opportunistic fungal infection as their course of disease is chronic and marked by less violent cytopenia then in e.g. Aplastic Anemia. Only neutropenia is regarded as independent risk factor for severe opportunistic infection in T-LGL patients.Case presentationWe report a case of a 53 year old patient with T-LGL, Immune-Thrombocytopenia (ITP) and combined antibody deficiency, who presented with fever and reduced general condition. The patient revealed a complicated infection involving the lungs and later the brain, with the presentation of vomiting and seizures. Broad microbiological testing of blood-, lung- and cerebrospinal fluid samples was inconclusive. In the absence of mycological proof, Aspergillus infection was confirmed by pathological examination of a brain specimen and finally successfully treated with liposomal amphotericin B and voriconazole, adopting a long-term treatment scheme.ConclusionsBeyond typical problems in the clinical practice involving fungal infections and hematologic malignancies, this case of invasive aspergillosis in a patient with T-LGL illustrates caveats in diagnosis, therapy and follow-up. Our data support careful ambulatory monitoring for patients with T-LGL, even in the absence of neutropenia. Especially those patients with combined hematologic malignancies and immune defects are at risk. Long-term treatment adhesion for 12 months with sufficient drug levels was necessary for sustained clearance from infection.

<p>An Overview of the Management of the Most Important Invasive Fungal Infections in Patients with Blood Malignancies</p>

“…and Aspergillus fumigatus Cerebral aspergillosis and pneumonia A 53 year old patient with LGL, Immune thrombocytopenia and combined antibody deficiency AMB and voriconazole No MRI, chest radiography, CT and HE Treated In cerebral involvement, prolonged treatment was recommended, and this patient showed no further relapse after 12 months of effective voriconazole treatment. 129 Inoue (2020) Cryptococcus species Cellulitis of the left mandible 31-year-old man with AML LAMB, flucytosine and fluconazole Surgical debridement HE Treated The surgical site healed after the operation. 130 Suleman (2019) Cryptococcus neoformans Cryptococcal meningitis and skin disease 60-year-old man with CLL AMB, flucytosine and fluconazole NO Blood and CSF culture Treated Physicians should be aware of possibility of disseminated cryptococcosis in patients with treatment-naïve CLL.…”

Promising effects of corticosteroid treatment in combination with antifungal agents in a patient with Aspergillus meningitis

“…Taking into consideration that outcomes of monotherapy vs. combination therapy could be an important point of comparison in previous reports of neuroaspergillosis, Karthic et al reported an expired case that was treated with VCZ, 11 Haroon and colleagues mentioned another expired case who received AMB, 12 but the overall results of combination therapy were more promising; Gruter et al reported a neuroaspergillosis patient (who also had thyroid cancer) receiving VCZ+ AMB+ ISZ who was cured 5 . Leroy et al 13 and Turki et al 14 both reported cured cases of neuroaspergillosis treated with VCZ + liposomal AMB, and of 5 cases described in Tattevin and colleagues' study, 3 were cured by combination therapy 10 …”

Antifungal Drugs TDM: Trends and Update

“…68–70 TDM is generally recommended, but the feasibility of recording CNS drug exposure depends on the possibility of using surgery or shunt devices. Documented indicative concentrations in the CSF are 1–4 mg/L for VRZ, 71–75 undetectable for CSP, PSZ, and ISZ, and are not predictive of treatment outcome. For anatomical brain samples, recently developed technologies (microdialysis, PET scan, and MALDI-MSI) can assess drug distribution or PK changes in the CNS.…”

“…236 Case reports included a combination of surgery or external ventricular drainage when possible, and drug regimens with combinations of either AmB or echinocandins 236 and high-dose TDM-guided azole with long-term follow-up of sequential treatments. 75,237,238 Furthermore, some CSF or brain tissue AF concentrations have been documented. 79,81 Thus, VRZ is still widely used for Aspergillus spp., although interest in ISZ is increasing 239 due to its favorable PK/PD and safety profiles.…”

“…AF TDM cases in real-life settings (pathogens, underlying diseases, 69,71–73,75,81 trends per year, 84,234,235,236,238,239,241,244,245,344–348 CNS 532–539 localization 541–566 ) 364,370,499,522,527–530 Trends are concerning a majority of mucomycosis and aspergillosis, in oncohematology and transplantation. VRZ, more recently PSZ tablets and ISZ are the most represented.…”