Transfusion Medicine and Hemotherapy最新文献

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: 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.

Background: Gestational alloimmune liver disease (GALD), previously known as neonatal hemochromatosis, is a rare maternal-fetal alloimmune disease causing severe fetal-neonatal liver failure. Understanding the immunological origin resulted in the concept of treatment with high-dose intravenous immunoglobins (IVIG) during gestation.

Methods: This retrospective single-center cohort study consists of seven women with index cases of GALD, followed by a total of ten IVIG-treated singleton pregnancies.

Results: Out of seven index pregnancies, five resulted in neonatal deaths. In a total of ten subsequent pregnancies all seven women at risk received antenatal IVIG (1g/kg body weight weekly) starting at median 14 weeks of gestation. Pregnancy courses were uneventful, except for one case of fetal growth restriction and preterm delivery due to severe preeclampsia. No severe maternal adverse effects of repetitive IVIG (median 23 applications) were observed. None of the infants from IVIG-treated women developed severe GALD. Two out of ten neonates displayed slightly abnormal laboratory parameters but did not require exchange transfusion or any other specific treatment. Based on standard laboratory data, we developed a scoring method to identify neonates at risk for GALD-associated liver failure.

Conclusion: This case series indicates that weekly antenatal IVIG treatment is highly efficient to prevent GALD-associated neonatal liver failure. In contrast to other cases series, there were no major maternal side effects. An introduced novel laboratory scoring system to decide on early postnatal intervention requires validation in a larger number of neonates.

Introduction: Many erythrocyte antibodies have been reported to cause hemolytic disease of the fetus and newborn (HDFN), but Lutheran (LU) alloantibodies are normally not involved in HDFN.

Case presentation: Here we report the obstetrical history of a 29-year-old woman with pregnancy complications due to an anti-LU1 antibody causing fetal anemia and the successful treatment with intrauterine transfusion (IUT). Nonimmune hematological causes for fetal anemia and the presence of further alloantibodies, notably antibodies against low-frequency antigens, could be ruled out. Swiss National Immunohematology Reference Laboratory in Bern carried out a monocyte monolayer assay. The monocyte index was >20%, indicating the presence of a clinical relevant antibody.

Conclusion: The diagnosis, acute management, and follow-up of neonates with fetal anemia still represent an important area of activity for maternity/neonatal services. To our knowledge, this is the first reported case of HDFN due to an anti-LU1 antibody requiring IUT.

Background: In general, the detection of the causative drug in patients who develop allergies related to drugs is very complicated or even impossible. To date, urine and serum samples from patients who have received the drug suspected to be associated with adverse drug reactions (ex vivo antigens) have rarely been used to detect metabolite-dependent antibodies (mdab) to red blood cells (RBCs). Here, we investigated whether ex vivo drug metabolism using primary human hepatocytes might be a better alternative for obtaining the metabolites needed for the assays.

Methods: Two serum samples containing mdab from 2 patients who had previously developed severe immune hemolytic anemia associated with diclofenac and 5-FU, respectively, were retested in the presence of urinary metabolites from patients and from ex vivo metabolism in primary human hepatocytes seeded in 2D monoculture.

Results: Both mdab tested were detectable with urine as a source of drug metabolites, and with ex vivo drug metabolites obtained from the hepatocyte cell culture, using enzyme-treated RBCs.

Conclusion: The results obtained in this study are encouraging, not only in terms of improving the detection of mdab to blood cells but also in other forms of allergies related to drugs. Ex vivo drug metabolism using hepatocyte cell culture may represent a standardized and controllable alternative to urine or serum samples for the detection of mdab to any affected human cells.

Background: Maternal alloimmunization can lead to significant perinatal morbidity and mortality. The rate of maternal alloimmunization reported is varied across the studies conducted in India. A systematic review will help in understanding the overall prevalence of alloimmunization. Additionally, the study aimed at understanding the factors affecting the rate of maternal alloimmunization.

Methods: A search of original articles reporting rate of alloimmunization among antenatal women published in English language from India was performed in Scopus, Google Scholar, MEDLINE, and CINAHL databases. Two independent teams, each comprising two reviewers, extracted data from the eligible studies. Meta-analysis was performed for cumulative estimates by binary random-effects model using the restricted maximum likelihood method.

Results: Fourteen studies published between 2011 and 2023 were included. The pooled prevalence of maternal alloimmunization was 2.0 per 100 (95% CI: 1.5-2.5) among antenatal women, with significant heterogeneity across studies. Anti-D was the most frequently identified antibody (56.39%), followed by anti-D + anti-C (10.68%) and anti-E (5.71%). Higher risk of alloimmunization was observed in women with Rhesus D-negative blood group, multigravida status, history of blood transfusion, and bad obstetric history.

Conclusion: Despite the availability of anti-D prophylaxis, over half of the alloimmunized women had anti-D antibodies, indicating potential gaps in prevention strategies. Further research is needed to understand these gaps and implement effective interventions to minimize this preventable cause of fetal and neonatal complications. For girls and women of reproductive age, providing prohylactic antigen-matched (Rh and Kell) red cell units when transfusion is needed may reduce the burden of red cell alloimmunization.