ABSTRACT
Chimeric antigen receptor-modified T cell (CAR-T) therapy is a promising novel immunotherapy for hematologic malignancies, and the diagnosis of infection after CAR-T infusion (CTI) presents challenges for clinicians. Plasma metagenomic next-generation sequencing (mNGS) has been shown to be a reliable diagnostic approach for infection, especially in immunocompromised patients. We aimed to investigate the diagnostic performance of plasma mNGS for infection in the first 30 days after CTI. A cohort of 153 patients who experienced a total of 170 febrile events during the first 30 days post-CTI were enrolled. Of these events, 51 were evaluated with both mNGS and CDM and 119 were assessed by conventional detection methods (CDM) only. We also explored the epidemiology of infections and differences in infection complications in cases with severe (>2) and moderate (≤2) cytokine release syndrome (CRS). Cases with febrile events were clinically divided into an infection group (IG) (95 of 170; 55.9%) and a noninfection group (NIG) (75 of 170; 44.1%). The sensitivity and specificity of mNGS for the diagnosis of infectious complications in the first 30 days after CTI were 69.2% and 89.2%, respectively, with the sensitivity superior to that of culture (P < .001). More infection cases assessed with both mNGS and CDM than those assessed with CDM only were laboratory-confirmed (63.9% versus 11.9%; P < .001). The serum C-reactive protein level was higher and the IFN-γ level was lower in the IG group, particularly in cases with CRS grade ≤2. Infection is a common complication in the first 30 days after CTI. The addition of mNGS to CDM improved the diagnostic yield, and mNGS showed relatively high sensitivity and specificity in post-CAR-T therapy febrile events.
Subject(s)
Receptors, Chimeric Antigen , Humans , Immunotherapy, Adoptive/adverse effects , High-Throughput Nucleotide Sequencing , Immunotherapy , Cytokine Release Syndrome , Fever/diagnosis , Fever/etiologyABSTRACT
The comparison of haploidentical G-CSF-mobilized peripheral blood and bone marrow transplantation (HBMT) for patients with myelodysplastic syndrome (MDS) and haploidentical G-CSF-primed peripheral blood stem cell transplantation (HPBSCT) remains unclear. We performed a retrospective analysis using a propensity score method on 140 MDS patients who received HPBSCT (n = 46) or HBMT (n = 94) with BU/CY as a conditioning regimen prior to transplantation at our center between June 2016 and June 2021. HBMT recipients were associated with a reduced incidence of grade III-IV acute GVHD (17.22% vs. 30.57%, p = 0.019) within 100 days, reduced 2-year transplant-related mortality (TRM) (14.29% vs. 28.94%, p = 0.045) and superior 2-year overall survival (OS) (81.6% vs. 66.0%, p = 0.027), progression-free survival (PFS) (80.9% vs. 61.2%, p = 0.015), and GVHD relapse-free survival (GRFS) (64.6% vs. 53.3%, p = 0.062) compared with HPBSCT, but 2-year relapse incidence (RI) (5.96% vs. 9.39%, p = 0.445) was not affected. Multivariate analysis revealed that a GPB/GBM mixture was the independent factor for a reduced incidence of grade III-IV acute GVHD (p = 0.018) and TRM (p = 0.048), improved OS (p = 0.029), PFS (p = 0.019) and GRFS (p = 0.072). Collectively, the use of a GPB/GBM mixture as stem cell grafts for haplo-HSCT in patients with MDS appears to be an optimal choice.
