A case report of the metagenomics next-generation sequencing for early detection of central nervous system mucormycosis with successful rescue in patient with recurrent chronic lymphocytic leukemia

Abstract

Background: Central nervous system (CNS) mucormycosis is insidious and difficult to diagnose. It progresses rapidly and causes high mortality. Rare cases have been reported during ibrutinib use, which have poor prognosis. Through this case, we share the experience of successful diagnosis and treatment. We also emphasize the importance of focusing on high-risk groups, early diagnosis and prompt management.

Case description: In this case, a 52-year-old patient was diagnosed with chronic lymphocytic leukemia (CLL) for more than 5 years. He was in remission after rituximab plus fludarabine and cyclophosphamide (RFC) regimen, and relapsed in the fourth year. During the ibrutinib monotherapy, the patient presented with sudden headache. Cranial imaging examination revealed a definite right occipitoparietal lobe mass with extensive edema. A rapid diagnosis of mucormycosis infection was made using metagenomic next-generation sequencing (mNGS). The patient at that time didn't have neutropenia, but he had hypogammaglobulinemia. The infection was treated with amphotericin B cholesteryl sulfate complex, posaconazole, and interventional surgery, and the treatment was successful. At the same time, we considered the control of disease progression in this relapsed patient with, as well as to the drug interaction with posaconazole. We chose the next generation Bruton's tyrosine kinase (BTK) inhibitor zanubrutinib as the treatment, whose safety has been identified. As of the submission date, the patient has been followed up for nearly 1 year, and his disease is stable.

Conclusions: When new clinical problems arise in recurrent CLL patients, it is important to identify multiple factors, especially the insidious fungal infections. In particular, the immunocompromised patients should be concerned. CNS mucormycosis is extremely deadly, the early diagnosis will improve the prognosis. In clinical practice, the gold standard diagnosis of mucormycosis is difficult to obtain through pathology. In this case, mNGS was applied to quickly diagnose mucormycosis, enabling earlier treatment and ameliorating the prognosis. Thus, it will help us to early detect this group of people who may be potentially infected. Current guidelines do not recommend the prophylactic use of antifungal agents in treated CLL patients. However, in patients with prior severe infection or hypogammaglobulinemia, intravenous immunoglobulin is recommended to reduce the associated infection rate.

Keywords: Case report; central nervous system mucormycosis (CNS); chronic lymphocytic leukemia (CLL); metagenomic next-generation sequencing (mNGS); zanubrutinib.

Figure 1

Changes in the cranial MRI of the patient. (A) MRI of the cerebellum (16 August 2021), T1W FLAIR; (B) MRI of the cerebellum (16 August 2021), T2W FLAIR; (C) MRI of the cerebellum (16 August 2021), DWI; (D) MRI of the cerebellum (31 August 2021), T1W FLAIR; (E) MRI of the cerebellum (31 August 2021), T2W FLAIR; (F) MRI of the cerebellum (31 August 2021), DWI; (G) MRI of the cerebellum (15 November 2021), T1W FLAIR; (H) MRI of the cerebellum (15 November 2021), T2W FLAIR; (I) MRI of the cerebellum (15 November 2021), DWI; (J) MRI of the cerebellum (14 March 2022), T1W FLAIR; (K) MRI of the cerebellum (14 March2022), T2W FLAIR; (L) MRI of the cerebellum (14 March 2022), DWI. MRI, magnetic resonance imaging; T1W FLAIR, T1-weighted-fluid-attenuated inversion recovery; T2W FLAIR, T2-weighted-fluid-attenuated inversion recovery; DWI, diffusion-weighted imaging.

Figure 2

Report of PMseq of CSF (distribution of the locations in the pathogen genome). PMseq, pathogenic microorganism DNA/RNA high-throughput genetic sequencing; CSF, cerebrospinal fluid; The “M” on the x-coordinate means the location of the genome.

Figure 3

Flow of diagnosis and treatment. CLL/SLL, chronic lymphocytic leukemia/ small lymphocytic leukemia; CR, complete remission; RFC, rituximab plus fludarabine and cyclophosphamide; IR, ibrutinib and rituximab; mNGS metagenomics Next-Generation Sequencing; CSF, cerebrospinal fluid; MRI, magnetic resonance imaging; SMZ, sulfamethoxazole; Pred, prednisone; mono, monotherapy; CNS, central nervous system.