Transfusion Medicine and Hemotherapy最新文献

Background: Dry eye disease (DED), as one of the most prevalent ocular surface diseases, is a multifactorial disorder disrupting tear film homeostasis and ocular surface integrity, profoundly impacts patients' quality of life. Conventional therapies such as artificial tears and anti-inflammatory agents provide transient relief but fail to address underlying pathological mechanisms and may induce complications with prolonged use.

Summary: Platelet-rich plasma (PRP), an autologous biologic agent enriched with growth factors (e.g., platelet-derived growth factor, transforming growth factor-β, epidermal growth factor), has emerged as a promising therapeutic strategy. PRP promotes corneal epithelial regeneration, reduces inflammation, and restores glandular function, offering a pathophysiologically targeted approach. Recent studies highlight synergistic benefits of combining PRP with agents like hyaluronic acid, stem cells, or nanomaterials, which enhance tear film stability and tissue repair. Despite encouraging preclinical and clinical outcomes, optimal protocols and long-term safety of PRP-based combination therapies remain under investigation.

Key messages: This review synthesizes current evidence on PRP's mechanisms, clinical efficacy, and innovative combinatorial approaches for DED, emphasizing the need for standardized trials to validate these strategies. Future integration of PRP with biologics, advanced materials, or laser therapies may revolutionize precision medicine in DED management.

Introduction: West Nile virus (WNV) is an arthropod-borne virus (arbovirus). It circulates in an enzootic cycle between ornithophilic mosquitoes as vectors and different avian species as reservoir hosts and/or for amplification but humans can be infected as accidental hosts. Since 2019, autochthonous mosquito-borne WNV infections in humans were reported in Germany indicating a continuous circulation in the affected areas. The animal and human infections were initially restricted to Central-East Germany in the first years. This article provides an update to the WNV epidemiology in Germany from 2022 to 2024.

Methods: Analysis was based on surveillance data and confirmatory testing for human and animal cases of WNV in Germany from 2022 to 2024.

Results: Since 2022, a slight annual spread became visible, which intensified in 2024 and caused numerous infections in northwest Germany, particularly among animals. Altogether, 80 confirmed human WNV infections were identified in 2022-2024, mostly among blood donors. Transfusion safety is maintained by donor deferral or testing of donations using nucleic acid amplification techniques (NAT) after a stay in an affected area. The vast majority of blood establishments test all donations during the transmission season in Germany from June to the end of November. In this way, roughly 2.2 million donations are screened annually, by that contributing significantly to WNV surveillance.

Conclusion: Confirmation of initially reactive screening tests is still a challenge as other flaviviruses, especially Usutu virus, are co-circulating. Specific NAT or next-generation sequencing are necessary for discrimination. To fully understand the WNV epidemic, combined results of human and veterinary surveillance including results of sequencing are needed. A One health approach is essential to identify affected areas and to ensure transfusion safety and public health.

[This corrects the article DOI: 10.1159/000546566.].

Background: Mesenchymal stromal/stem cells (MSCs) may be a useful therapy for severe acute graft-versus-host disease (GVHD).

Methods: Patients who developed steroid-refractory grade II-IV acute GVHD were randomly assigned to treatment with one infusion of third-party 2 × 10 E⁶/kg bone marrow (BM)-MSCs (n = 12) or placebo (n = 11). The median cell dose applied was 2.2 × 10 E⁶/kg (range 1.7-4.2). The median age was 37 and 47 years in the two groups (p = 0.24), respectively.

Results: At day 28, the BM-MSC group had six (50%) complete responders and 2 patients (17%) with a partial response. In the placebo group, the corresponding figures were three (27%) complete and three (27%) partial responders (p = 0.68). Transplantation-related mortality (TRM) 100 days after treatment was 17% in the BM-MSC group and 27% in the placebo group. At 1 year, TRM was 33% and 36% in the two groups, respectively (p = 0.59). The 100-day survival rate was 83% in the BM-MSC group and 73% in the placebo group. Five-year survival in all patients was 42% and 45% in the two groups, respectively (p = 0.87).

Conclusion: Although only a few patients were included in the trial, a single dose of BM-MSCs did not seem to be an effective therapy for steroid-refractory acute GVHD.

Introduction: Parvovirus B19 (B19) exhibits moderate resistance to the pathogen reduction methods employed during the production of platelet concentrates. In Switzerland, nucleic acid testing (NAT) for B19 is conducted for plasma fractionation; however, its results are not mandatory for the release of blood products.

Case presentation: We describe a case of B19 infection in an immunosuppressed, seronegative patient who received a pooled platelet concentrate treated with UVA light and amotosalen. Although the patient remained clinically asymptomatic, the infection was confirmed through laboratory findings, including rising viremia, seroconversion, and mild hematologic changes. We report the clinical course in detail, including treatments and co-medications. Phylogenetic analysis of the viral genome confirmed a direct link between the transfusion and the infection.

Conclusion: This case highlights that, similar to other infectious agents, Parvovirus B19 can be transmitted through pathogen-reduced blood products. It emphasizes the necessity for established surveillance procedures to detect such transmissions and ensure timely clinical intervention in affected patients.

Introduction: This study assesses HemoCue Plasma/Low Hb Analyzer (HemoCue) as an alternative to spectrophotometry for measuring free hemoglobin (fHb) in blood product quality control procedures.

Methods: We analyzed a total number of 100 leucocyte-depleted erythrocyte concentrate (EC) samples stored for 39-43 days and 56 frozen plasma (FP) unit samples from Fresenius (F) and Macopharma (M) bags.

Results: Median fHb measured for EC with HemoCue was 0.200 g/dL (IQR 0.100-0.260) (F) and 0.160 g/dL (0.110-0.200) (M) compared to 0.170 g/dL (0.109-0.242) (F) and 0.141 g/dL (0.101-0.207) (M) via spectrophotometry. Median fHb measured in FP with HemoCue was 0.010 g/dL (IQR 0.010-0.030) (F) and 0.020 g/dL (0.010-0.040) (M) compared to 0.003 g/dL (0.002-0.003) (F) and 0.001 g/dL (0.000-0.002) (M) using spectrophotometry. For EC, overall correlation between methods was strong for F (r _s = 0.87; CI: 0.78-0.96) and for M (r _s = 0.74; CI: 0.51-0.96). Bland-Altman analysis for EC revealed a median difference of 0.02 g/dL (-0.10 to 0.23) (F) and 0.00 g/dL (-0.08 to 0.14) (M) comparing HemoCue and spectrophotometer. For FP, Bland-Altman analysis revealed a median difference of 0.01 g/dL (0.00-0.08) (F) and 0.02 g/dL (0.00-0.14).

Conclusion: While obtained results were highly similar using both devices when assessing fHb in EC, HemoCue showed a consistent overestimation of fHb in FP samples compared to spectrophotometry. HemoCue demonstrated acceptable intraday and interday precision across concentration ranges and offers operational advantages, including faster turnaround times. Altogether in quality control analyses, HemoCue turned out to be a valuable tool for fHb measurements in EC with some limitations for FP.

Introduction: Hepatitis E virus (HEV) can cause transfusion-transmitted (TT) infections. Therefore, in many countries, blood donor screening for HEV RNA has been established. The amount of infectious HEV RNA concentration in blood donations and screening strategy (pool size, single-sample testing) are still debated.

Methods: Blood donations, taken before the universal blood donor screening for HEV RNA, were investigated retrospectively for HEV RNA. Recipients of an HEV RNA-positive blood product were traced by look-back procedure. Archive samples of these recipients were investigated for TT-HEV infection by HEV RNA and anti-HEV IgG testing. HEV RNA concentration in the donor and in the transfused blood product was determined.

Results: In 85/75,905 donations (0.1%), HEV RNA was detectable. A total of 28 recipients of 139 blood products from these donations could be further investigated. In 2/28 (7.1%) recipients, a possible TT-HEV infection occurred, but sequence analysis between donor and recipient could not be performed. HEV RNA concentration could be determined in 23 blood products and ranged from 10.9 IU/mL to 116,400 IU/mL donor plasma and absolute 120 IU-8,748,000 IU in the final blood product. In the cases of possible TT-HEV infection, HEV RNA concentration was 62,880 IU/mL donor plasma, according to 691,680-943,200 in the red blood cell concentrate and 593 IU/mL donor plasma, according to 8,302-11,267 IU in the pooled platelet concentrate.

Conclusion: Only a minority of HEV RNA-positive blood products caused a TT-HEV infection. With the limitation of the low number of investigated cases, even in blood products, which were contaminated with extremely high HEV RNA concentrations, there was no evidence for TT-HEV infection. Blood donor screening for HEV RNA by pooled samples should be favored over single-sample testing.

Introduction: The rare p phenotype, characterized by the absence of P, P1, and P^k antigens, produces anti-PP1P^k that can cause severe hemolytic reactions and recurrent miscarriages. This phenotype is rare globally but shows notable prevalence in the Swedish population. This study focuses on the molecular characterization of 6 Indian patients to provide further insight into the genetic basis of the p phenotype.

Methods: A targeted next-generation sequencing assay covering 51 genes associated with 41 blood group systems was utilized to investigate the molecular basis of the A4GALT gene in 6 patients with a serologically confirmed p phenotype. The results were analyzed and annotated using bioinformatics tools, including the Integrative Genomics Viewer, with novel variants confirmed by Sanger sequencing. Family members were also screened to identify potential rare donors.

Results: Genomic analysis revealed novel and rare variants in the A4GALT gene, all confirming the p phenotype. Five frameshift variants (c.72dupC, c.218delG, c.592delC, c.972_997del, and c.547_548del) and one nonsense variant (c.C392G) were detected, resulting in truncated, non-functional proteins. The p phenotype was confirmed in a subset of family members, identifying three new donors for rare blood transfusion requirements.

Conclusion: This study presents the molecular characterization of the p phenotype in Indian patients, identifying novel variants not yet registered in the ISBT database. These findings enhance understanding of the p phenotype and highlight the significance of family screening for identifying rare blood donors. The study underscores the critical need for rare donor registries, especially for patients at high risk of severe hemolytic reactions during transfusion.

Introduction: The clinical application of cell-based immunotherapies is a rapidly emerging field, and recent advances in gene therapy have opened up a new era of innovative treatment approaches. Introducing a specific T-cell receptor (TCR) against viral epitopes or chimeric antigen receptor (CAR) into T cells and effector cells allows reprogramming of their specificity and utilization for advanced therapeutic applications in infectious diseases and virus-induced malignancies. Many technologies have been developed to genetically engineer T cells, and existing databases in silico predict or describe identified viral epitopes, TCRs, or B-cell receptors (BCRs). However, their therapeutic application is still hampered by limited knowledge on their clinical impact.

Methods: An open-access online resource was developed, integrating a data-mining algorithm scoring the epitopes, TCRs, and BCRs (ETB database) according to clinical evidence.

Results: We hereby present a new level of clinical evidence-based knowledge transfer for selecting individual protective TCRs or BCRs for therapeutic application. The database is publicly available at https://app.bitcare.de/epitopeFrontend/.

Conclusion: Redirecting T-cell specificity by genetic engineering using clinically protective TCR or CAR sequences will not only bring significant progress to the field of adoptive T-cell therapies but also lay the groundwork for broader applications such as off-the-shelf approaches.