Abstract
Central nervous system (CNS) complications can occur in 9%–15% of patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The clinical manifestations of the CNS complications are non-specific, with most of them being disturbances of consciousness, convulsions, headaches, fever, and epilepsy, making it difficult to infer the cause of the complications based on clinical manifestations. We retrospectively analyzed the sensitivity and feasibility of metagenomic next generation sequencing (mNGS) in the diagnosis of CNS infections after allo-HSCT. Lumbar punctures were performed on 20 patients with CNS symptoms after receiving alternative donor HSCT(AD-HSCT) at the Affiliated Cancer Hospital of Zhengzhou University from February 2019 to December 2020, and their cerebrospinal fluid (CSF) was collected. The mNGS technique was used to detect pathogens in the CSF. Routine CSF testing, biochemical analyses, G experiments, GM experiments, ink staining, acid-fast staining, and bacterial cultures were carried out, and quantitative PCR (qPCR) tests were used to detect cytomegalovirus (CMV), Epstein-Barr virus (EBV), BK polyomavirus (BKPyV), and human alphaherpesvirus (HHV). A total of 29 tests were performed with 21 of them being positive. Of the five negative patients, three were diagnosed with a posterior reversible encephalopathy syndrome, one as having transplantation-associated thrombotic microangiopathy, and one with transient seizure caused by hypertension. Fifteen patients tested positive, of which four had single infections and eleven had mixed infections. Five cases of fungal infections, six cases of bacterial infections, and 13 cases of viral infections were detected. Among the 13 cases of viral infections, ten cases were CMV(HHV-5); three were BKPyV; two were Torque teno virus (TTV); Two were HHV-1,two were EBV(HHV4), and one each of HpyV5 and HHV-6B. Thirteen patients tested positive for virus while the qPCR detection method of 6 identical specimens were below the minimum detection limit(<1×103 U/ml). The mNGS technique is highly sensitive, and it can be used to diagnose CNS infections after allo-HSCT.
Highlights
IntroductionCentral nervous system (CNS) complications can occur in 9%– 15% of patients after allogeneic hematopoietic stem cell transplantations (allo-HSCT) (Schmidt-Hieber et al, 2016; Das et al, 2020) with the common causes being mainly the posterior reversible encephalopathy syndrome (PRES), transplant-related thrombotic microangiopathies (TA-TMA), CNS graft versus host disease (CNS-GVHD), CNS infiltration of malignant disease, CNS infections and non-specific neurological symptoms (Chaudhary et al, 2017; Maffini et al, 2017; Balaguer-Rosello et al, 2019)
Routine CSF testing, biochemical analyses, G experiments (There is no fungal infection below 70 pg/ml, 70-95 pg/ml is the observation period, continuous testing is given, and deep fungal infection is suspected if it is greater than 95pg/ml), GM experiments(Less than 0.65 ug/L is negative, greater than 0.85 ug/L is positive), ink staining, acid-fast staining, and bacterial cultures were performed, and quantitative PCR was used to detect the cytomegalovirus (CMV), Epstein-Barr virus (EBV), BK polyomavirus (BKPyV), and human alphaherpesvirus (HHV)
Allo-HSCT patients are a high-risk group for Central nervous system (CNS) infections, with a total incidence of up to 15%, and most of them occurring within six months after transplantation (Pruitt et al, 2013)
Summary
Central nervous system (CNS) complications can occur in 9%– 15% of patients after allogeneic hematopoietic stem cell transplantations (allo-HSCT) (Schmidt-Hieber et al, 2016; Das et al, 2020) with the common causes being mainly the posterior reversible encephalopathy syndrome (PRES), transplant-related thrombotic microangiopathies (TA-TMA), CNS graft versus host disease (CNS-GVHD), CNS infiltration of malignant disease, CNS infections and non-specific neurological symptoms (Chaudhary et al, 2017; Maffini et al, 2017; Balaguer-Rosello et al, 2019). CNS infections are still the main cause of CNS complications after transplantation, with an incidence rate of up to 15% (Schmidt-Hieber et al, 2016). The incidence of alloHSCT is significantly higher than that of autologous HSCT, with the fatality rate being high (Chaudhary et al, 2017). This is a risk factor for poor prognosis in patients after alloHSCT (Dowling et al, 2018). For CNS infections after transplantation, traditional detection methods cannot meet clinical needs by offering a quick and accurate means to diagnose the infections and the types of infectious pathogens. Rapid and accurate detection methods for pathogenic microorganisms have become the focus of current research
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