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.
Extramedullary relapse (EMR) rarely occurs after allogeneic hematopoietic stem cell transplantation (HSCT) in leukemia. This study was to investigate the clinical characteristics of EMR. We retrospectively investigated 316 consecutive patients undergoing HSCT for acute leukemia or chronic myeloid leukemia (CML) at 2 institutions between January 2012 and February 2017. Furthermore, we analyzed and compared the risk factors and outcomes between EMR and bone marrow relapse (BMR). The 5-year cumulative incidence of EMR was 14.1%. The EMR incidence in acute myeloid leukemia, lymphoblastic leukemia, and CML was 17.5%, 18.9%, and 5.3%, respectively. CML had a lower EMR incidence rate. Compared to the BMR group, the EMR group had a longer median relapse-free time (10.5 months vs 5 months, P = .02), and the EMR group had a higher incidence rate of chronic graft-versus-host disease (50.0% vs 20.9%, P = .009). EMR had better estimated 3-year survival rates post-HSCT, and post-relapse, than did BMR (39.5% vs 9.5%, P < .001, and 21.9% vs 10.8%, P = .001). Multivariate analysis identified that adverse cytogenetics (hazard ratio [HR] = 9.034, P < .001) and extramedullary leukemia before HSCT (HR = 2.685, P = .027) were the independent risk factors for EMR after HSCT. In the EMR group, patients who achieved complete remission (CR) had a significantly better, estimated 3-year survival than did patients who did not achieve CR (38.4% vs 14.3%, P = .014). EMR is a significant contributor to mortality after HSCT, which appears to be resistant to most of the current therapies. Establishing effective strategies for EMR is important in improving outcomes after HSCT.
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