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Introduction Morbidity and mortality in patients with hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) are frequently caused by graft rejection or graft-versus-host disease (GvHD) and increased by [...], BACKGROUND. Adoptive transfer of EBV-specific T cells can restore specific immunity in immunocompromised patients with EBV-associated complications. METHODS. We provide results of a personalized T cell manufacturing program evaluating donor, patient, T cell product, and outcome data. Patient-tailored clinical-grade EBV-specific cytotoxic T lymphocyte (EBV-CTL) products from stem cell donors (SCDs), related third-party donors (TPDs), or unrelated TPDs from the allogeneic T cell donor registry (alloCELL) at Hannover Medical School were manufactured by immunomagnetic selection using a CliniMACS Plus or Prodigy device and the EBV PepTivators EBNA-1 and Select. Consecutive manufacturing processes were evaluated, and patient outcome and side effects were retrieved by retrospective chart analysis. RESULTS. Forty clinical-grade EBV-CTL products from SCDs, related TPDs, or unrelated TPDs were generated for 37 patients with refractory EBV infections or EBV-associated malignancies with and without a history of transplantation, within 5 days (median) after donor identification. Thirty-four patients received 1-14 EBV-CTL products (fresh and cryopreserved). EBV-CTL transfer led to a complete response in 20 of 29 patients who were evaluated for clinical response. No infusion-related toxicity was reported. EBV-specific T cells in patients' blood were detectable in 16 of 18 monitored patients (89%) after transfer, and their presence correlated with clinical response. CONCLUSION. Personalized clinical-grade manufacture of EBV-CTL products via immunomagnetic selection from SCDs, related TPDs, or unrelated TPDs in a timely manner is feasible. Overall, EBV-CTLs were clinically effective and well tolerated. Our data suggest EBV-CTL transfer as a promising therapeutic approach for immunocompromised patients with refractory EBV-associated diseases beyond HSCT, as well as patients with preexisting organ dysfunction. TRIAL REGISTRATION. Not applicable. FUNDING. This study was funded in part by the German Research Foundation (DFG, 158989968/SFB 900), the Deutsche Kinderkrebsstiftung (DKS 2013.09), Wilhelm-Sander-Stiftung (reference 2015.097.1), Ellen-Schmidt-Program of Hannover Medical School, and German Federal Ministry of Education and Research (reference 01E00802).

Introduction: Chimeric antigen receptor positive T cell (CAR-T cell) treatment became standard therapy for relapsed or refractory hematologic malignancies, such as non-Hodgkin's lymphoma and multiple myeloma. Owing to the rapidly progressing field of CAR-T cell therapy and the lack of generally accepted treatment guidelines, we hypothesized significant differences between centers in the prevention, diagnosis, and management of short- and long-term complications. Methods: To capture the current CAR-T cell management among German centers to determine the medical need and specific areas for future clinical research, the DAG-HSZT (Deutsche Arbeitsgemeinschaft für Hämatopoetische Stammzelltransplantation und Zelluläre Therapie; German Working Group for Hematopoietic Stem Cell Transplantation and Cellular Therapy) performed a survey among 26 German CAR-T cell centers. Results: We received answers from 17 centers (65%). The survey documents the relevance of evidence in the CAR-T cell field with a homogeneity of practice in areas with existing clinical evidence. In contrast, in areas with no – or low quality – clinical evidence, we identified significant variety in management in between the centers: management of cytokine release syndrome, immune effector cell-related neurotoxicity syndrome, IgG substitution, autologous stem cell backups, anti-infective prophylaxis, and vaccinations. Conclusion: The results indicate the urgent need for better harmonization of supportive care in CAR-T cell therapies including clinical research to improve clinical outcome. [ABSTRACT FROM AUTHOR]

Introduction: Men are generally more susceptible to bacterial infections than women. Central venous catheters (CVCs), often used to administer systemic treatment in patients with cancer, are an important source of infection. However, little is known about sex-specific differences of CVC-related bloodstream infections (CRBSIs) in patients with cancer. This study aimed to compare CRBSIs in men versus women in a large cohort of patients with cancer. Methods: Data were derived from the SECRECY registry including nonselected patients with centrally inserted non-tunneled internal jugular or subclavian vein CVCs in 10 hematology and oncology sites in Germany. Only CRBSIs classified as definite CRBSI (dCRBSI) or probable CRBSI were included, and the combination of both was summarized as dpCRBSI. CVCs were matched 1:1 for underlying disease, anatomic site of CVC insertion, type of CVC dressing, antimicrobial coated CVC, complicated CVC insertion, and CVC in situ time by propensity score matching (PSM). Endpoints were CRBSI rates and incidences in CVCs inserted in men versus women. Results: A total of 5,075 CVCs registered from March 2013 to March 2024 were included in the analysis, of which 3,024 comprise the PSM cohort. A total of 1,512 (50.0%) CVCs were inserted in men. Underlying diseases mainly were hematological malignancies (96.4%). While there was no statistically significant difference between men and women in the dCRBSI rate (5.4% vs. 4.1%; p = 0.12) and the dCRBSI incidence (3.8 vs. 2.9/1,000 CVC days; p = 0.11), the rate of dpCRBSI (9.9% vs. 6.7%; p = 0.002) and the dpCRBSI incidence (7.0 vs. 4.7/1,000 CVC days; p = 0.002) were significantly higher in men versus women. The proportion of coagulase-negative staphylococci as causative agent of both dCRBSI and dpCRBSI was higher in men than in women (58.8% vs. 41.2%; p = 0.07 and 61.5% vs. 38.5%; p = 0.002, respectively). A multivariable regression revealed neutropenia as an independent risk factor for dCRBSI and male sex as risk factor for dCRBSI and dpCRBSI. Conclusion: In patients with hematological malignancies, men have a higher risk of CRBSI than women. This finding may be attributed to the high number of jugular vein-inserted CVCs, which in men may be associated with higher rates of skin colonization than in women. Special preventive measures such as earlier removal of CVCs in men may be studied in future. Introduction: Men are generally more susceptible to bacterial infections than women. Central venous catheters (CVCs), often used to administer systemic treatment in patients with cancer, are an important source of infection. However, little is known about sex-specific differences of CVC-related bloodstream infections (CRBSIs) in patients with cancer. This study aimed to compare CRBSIs in men versus women in a large cohort of patients with cancer. Methods: Data were derived from the SECRECY registry including nonselected patients with centrally inserted non-tunneled internal jugular or subclavian vein CVCs in 10 hematology and oncology sites in Germany. Only CRBSIs classified as definite CRBSI (dCRBSI) or probable CRBSI were included, and the combination of both was summarized as dpCRBSI. CVCs were matched 1:1 for underlying disease, anatomic site of CVC insertion, type of CVC dressing, antimicrobial coated CVC, complicated CVC insertion, and CVC in situ time by propensity score matching (PSM). Endpoints were CRBSI rates and incidences in CVCs inserted in men versus women. Results: A total of 5,075 CVCs registered from March 2013 to March 2024 were included in the analysis, of which 3,024 comprise the PSM cohort. A total of 1,512 (50.0%) CVCs were inserted in men. Underlying diseases mainly were hematological malignancies (96.4%). While there was no statistically significant difference between men and women in the dCRBSI rate (5.4% vs. 4.1%; p = 0.12) and the dCRBSI incidence (3.8 vs. 2.9/1,000 CVC days; p = 0.11), the rate of dpCRBSI (9.9% vs. 6.7%; p = 0.002) and the dpCRBSI incidence (7.0 vs. 4.7/1,000 CVC days; p = 0.002) were significantly higher in men versus women. The proportion of coagulase-negative staphylococci as causative agent of both dCRBSI and dpCRBSI was higher in men than in women (58.8% vs. 41.2%; p = 0.07 and 61.5% vs. 38.5%; p = 0.002, respectively). A multivariable regression revealed neutropenia as an independent risk factor for dCRBSI and male sex as risk factor for dCRBSI and dpCRBSI. Conclusion: In patients with hematological malignancies, men have a higher risk of CRBSI than women. This finding may be attributed to the high number of jugular vein-inserted CVCs, which in men may be associated with higher rates of skin colonization than in women. Special preventive measures such as earlier removal of CVCs in men may be studied in future. [ABSTRACT FROM AUTHOR]