Relevance of different prognostic scores in primary CNS lymphoma in the era of intensified treatment regimens: A retrospective, multicenter analysis of 174 patients.

OBJECTIVES: Treatment intensification (including consolidative high-dose chemotherapy with autologous stem cell transplantation [HDT-ASCT]) significantly improved outcome in primary central nervous system lymphoma (PCNSL) patients. METHODS: We conducted a multicenter, retrospective analysis of newly diagnosed PCNSL patients, treated with intensified treatment regimens. The following scores were evaluated in terms of overall survival (OS) and progression-free survival (PFS): Memorial Sloan-Kettering Cancer Center (MSKCC), International Extranodal Lymphoma Study Group (IELSG), and three-factor (3F) prognostic score. Further, all scores were comparatively investigated for model quality and concordance. RESULTS: Altogether, 174 PCNSL patients were included. One hundred and five patients (60.3%) underwent HDT-ASCT. Two-year OS and 2-year PFS for the entire population were 73.3% and 48.5%, respectively. The MSKCC (p = .003) and 3F score (p < .001), but not the IELSG score (p = .06), had the discriminatory power to identify different risk groups for OS. In regard to concordance, the 3F score (C-index [0.71]) outperformed both the MSKCC (C-index [0.64]) and IELSG (C-index [0.53]) score. Moreover, the superiority of the 3F score was shown for PFS, successfully stratifying patients in three risk groups, which also resulted in the highest C-index (0.66). CONCLUSION: The comparative analysis of established PCNSL risk scores affirm the clinical utility of the 3F score stratifying the widest prognostic spectrum among PCNSL patients treated with intensified treatment approaches.

Chlorhexidine gluconate-coated gel pad dressings for prevention of central venous catheter-related bloodstream infections in patients with hematologic diseases or autologous stem cell transplantation: A registry-based matched-pair analysis.

OBJECTIVES: Chlorhexidine gluconate (CHG)-coated gel pad dressings for central venous catheter (CVC) may prevent CVC-related bloodstream infections (CRBSI). However, real-world data showing beneficial effects in patients with hematologic malignancies are scarce. METHODS: In a matched-pair analysis with data from a multicenter CVC registry, non-tunneled jugular and subclavian vein CVC in adults with hematologic malignancies or germ cell tumors (including patients receiving autologous hematopoietic stem cell transplantation [ASCT]) with CHG were compared with non-CHG dressings. The primary endpoint was definite CRBSI rate within 14 days (dCRBSI14) of CVC insertion; secondary endpoints were combined rate of definite or probable CRBSI within 14 days (dpCRBSI14), overall (dpCRBSI), and CRBSI incidences of all estimates. RESULTS: In total, 2070 CVCs were assessed. There was no statistically significant difference in dCRBSI14 (2.3% vs. 3.5%) between patients with and without CHG gel dressings. Likewise, with regards to dpCRBSI14 (6.2% vs. 6.3%) and the overall dpCRBSI rate (9.2% vs. 10.5%), no significant difference was detected. Furthermore, dCRBSI14 incidence (2.0 vs. 3.2/1000 CVC days), dpCRBSI14 incidence (5.4 vs. 5.6/1000 CVC days), and overall CRBSI incidence (5.5 vs. 6.0/1000 CVC days) showed no significant differences. CONCLUSIONS: CRBSI rates were not reduced by the use of CHG gel dressings in patients with hematologic malignancies and/or ASCT.

Tigecycline as salvage treatment of febrile neutropenia in patients with haematological malignancies-a retrospective single-centre analysis of 200 cases.

Tigecycline has been used to treat patients with febrile neutropenia (FN). This study aims to analyse the effectiveness of tigecycline as salvage treatment of FN. Patients records from 09/2004 to 04/2019 were reviewed. Cases were eligible if fever persisted/recurred (p/r-FN) after 3 days of second-line treatment with a carbapenem, and were divided into three groups: switch to tigecycline (TGC group), switch to other antibiotics (OAB group), and no switch (W&W group). The primary endpoint was response rate (defervescence for ≥ 7 days or at least until discharge); the key secondary endpoint was 30-day mortality rate. Two hundred cases from 176 patients (median 59 years; 53.5% men) treated were included, mostly acute myeloid leukaemias (61.0%). 45.5% of cases were in the TGC group (in combination with an anti-pseudomonal antibiotic, mostly ceftazidime [95.6%]); 35.5% were in the OAB and 19.0% in the W&W group. There was no significant difference in response rates (TGC, 73.6%; OAB, 62.0%; W&W, 78.9%; p = 0.12) or 30-day mortality rates (TGC, 7.7%; OAB, 7.0%; W&W, 5.3%; p = 0.94). Tigecycline plus an anti-pseudomonal antibiotic does not improve response or 30-day mortality rate compared to other antibiotics in patients with p/r-FN. Also, in some cases, no switch in antibiotics may be necessary at all.

N-glycosylation controls inflammatory licensing-triggered PD-L1 upregulation in human mesenchymal stromal cells.

Mesenchymal stromal cells (MSCs) are characterized by their multipotency, regenerative potential, and immunoregulatory properties. Nowadays, MSCs represent a promising cell-therapeutic option for hyperinflammatory conditions such as graft-vs-host disease following allogeneic hematopoietic stem cell transplantation. A better understanding of their biology is a prerequisite for improving their treatment efficacy. Emerging evidence suggests that immunosuppressive properties are not constitutively active in MSCs. Instead, microenvironmental inflammatory stimuli such as the cytokines interferon (IFN)-γ or tumor necrosis factor (TNF)-α license MSCs to acquire a tolerance-promoting phenotype. The immunological checkpoint molecule programmed death-ligand 1 (PD-L1) is an important regulator of T-cell responses. Binding of PD-L1 to the programmed cell death protein 1 (PD-1) receptor on T-cells suppresses their activation, proliferation, and induces apoptosis. Previous studies have revealed that cell surface expression and secretion of PD-L1 are part of the MSCs' immunomodulatory armamentarium. Here, we report that inflammatory licensing leads to an enhanced PD-L1 cell surface expression and secretion, which are both accompanied by an increased posttranslational protein N-glycosylation. These post-translational modifications have been shown to be critical for key biological processes such as cell trafficking, receptor signaling, and immunohomeostasis. In fact, promoting N-glycosylation in MSCs yielded increased PD-L1 levels. We report for the first time that PD-L1 N-glycosylation plays a decisive role for its transport to the MSCs' cell surface and its subsequent secretion (in response to proinflammatory trigger). Our data offer insights into a novel regulatory mechanism with the potential to be exploited as a means to foster the immunosuppressive potency of human MSCs.