-
Transfusion May 2024The increasing demand for umbilical cord blood (UCB) used in stem cell transplantation led to the establishment of cord blood (CB) banks worldwide. These include public...
BACKGROUND
The increasing demand for umbilical cord blood (UCB) used in stem cell transplantation led to the establishment of cord blood (CB) banks worldwide. These include public foreign donor banks and private family-directed donor banks. Recently, our department has introduced a third banking model within a private-public-partnership. This hybrid banking allows for storage of family-directed CB units, while also getting Human leukocyte antigen (HLA)-typed and included in the national stem cell donor registry. So if the need arises, the HLA-compatible CB unit can be released to an unrelated recipient as a foreign donor stem cell graft.
OBJECTIVES
The aim of this study was to evaluate women's perspectives on the different CB banking options as well as retrospective satisfaction with their decisions.
METHODS
We performed a prospective survey study in postpartum women, using a validated questionnaire.
RESULTS
A total of 157 women were included in this survey study; 68% of them decided to have their UCB stored or donated. Among those women, 25% of them opted for hybrid storage, 72% of respondents stored UCB publicly, and 3% decided for private family-directed storage.
CONCLUSIONS
Our study shows the potential of hybrid banking as an attractive UCB storage option, as an alternative to family-directed banking rather than a substitute for public donation. Hybrid storage potentially combines advantages of family-directed banking as well as unrelated CB donation expanding the number of registered CB units available for transplantation and giving every pregnant woman the possibility to store UCB.
PubMed: 38746954
DOI: 10.1111/trf.17858 -
Transfusion Medicine and Hemotherapy :... Apr 2024Primary human blood cells represent an essential model system to study physiology and disease. However, human blood is a limited resource. During healthy donor...
INTRODUCTION
Primary human blood cells represent an essential model system to study physiology and disease. However, human blood is a limited resource. During healthy donor plateletpheresis, the leukoreduction system chamber (LRSC) reduces the leukocyte amount within the subsequent platelet concentrate through saturated, fluidized, particle bed filtration technology. Normally, the LRSC is discarded after apheresis is completed. Compared to peripheral blood, LRSC yields 10-fold mononuclear cell concentration.
METHODS
To explore if those retained leukocytes are attractive for research purposes, we isolated CD3+ T cells from the usually discarded LRSCs via density gradient centrifugation in order to manufacture CD19-targeted chimeric antigen receptor (CAR) T cells.
RESULTS
Immunophenotypic characterization revealed viable and normal CD4+ and CD8+ T-cell populations within LRSC, with low CD19+ B cell counts. Magnetic-activated cell sorting (MACS) purified CD3+ T cells were transduced with CD19 CAR-encoding lentiviral self-inactivating vectors using concentrated viral supernatants. Robust CD19 CAR cell surface expression on transduced T cells was confirmed by flow cytometry. CD19 CAR T cells were further enriched through anti-CAR MACS, yielding 80% CAR+ T-cell populations. In vitro CAR T cell expansion to clinically relevant numbers was achieved. To prove functionality, CAR T cells were co-incubated with the human CD19+ B cell precursor leukemia cell line Nalm6. Compared to unmodified T cells, CD19 CAR T cells effectively eradicated Nalm6 cells.
CONCLUSION
Taken together, we can show that lymphocytes isolated from LRSCs of plateletpheresis sets can be efficiently used for the generation of functional CAR T cells for experimental purposes.
PubMed: 38584695
DOI: 10.1159/000532130 -
Frontiers in Immunology 2024Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for many hematologic malignancies as well as non-malignant conditions. Part... (Review)
Review
Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for many hematologic malignancies as well as non-malignant conditions. Part of the curative basis underlying HSCT for hematologic malignancies relies upon induction of the graft versus leukemia (GVL) effect in which donor immune cells recognize and eliminate residual malignant cells within the recipient, thereby maintaining remission. GVL is a clinically evident phenomenon; however, specific cell types responsible for inducing this effect and molecular mechanisms involved remain largely undefined. One of the best examples of GVL is observed after donor lymphocyte infusions (DLI), an established therapy for relapsed disease or incipient/anticipated relapse. DLI involves infusion of peripheral blood lymphocytes from the original HSCT donor into the recipient. Sustained remission can be observed in 20-80% of patients treated with DLI depending upon the underlying disease and the intrinsic burden of targeted cells. In this review, we will discuss current knowledge about mechanisms of GVL after DLI, experimental strategies for augmenting GVL by manipulation of DLI (e.g. neoantigen vaccination, specific cell type selection/depletion) and research outlook for improving DLI and cellular immunotherapies for hematologic malignancies through better molecular definition of the GVL effect.
Topics: Humans; Transplantation, Homologous; Lymphocyte Transfusion; Graft vs Host Disease; Hematologic Neoplasms; Lymphocytes; Leukemia
PubMed: 38558819
DOI: 10.3389/fimmu.2024.1328858 -
Journal of Veterinary Internal Medicine 2024Red blood cell (RBC) storage promotes biochemical and morphological alterations, collectively referred to as storage lesions (SLs). Studies in humans have identified... (Observational Study)
Observational Study
BACKGROUND
Red blood cell (RBC) storage promotes biochemical and morphological alterations, collectively referred to as storage lesions (SLs). Studies in humans have identified leukoreduction (LR) as a critical processing step that mitigates SLs. To date no study has evaluated the impact of LR on metabolic SLs in canine blood units using omics technologies.
OBJECTIVE
Compare the lipid and metabolic profiles of canine packed RBC (pRBC) units as a function of LR in fresh and stored refrigerated (up to 42 days) units.
ANIMALS
Packed RBC units were obtained from 8 donor dogs enrolled at 2 different Italian veterinary blood banks.
STUDY DESIGN AND METHODS
Observational study. A volume of 450 mL of whole blood was collected using Citrate-Phosphate-Dextrose-Saline-Adenine-Glucose-Mannitol (CPD-SAGM) transfusion bags with a LR filter to produce 2 pRBC units for each donor, without (nLR-pRBC) and with (LR-pRBC) LR. Units were stored in the blood bank at 4 ± 2°C. Sterile weekly samples were obtained from each unit for omics analyses.
RESULTS
A significant effect of LR on fresh and stored RBC metabolic phenotypes was observed. The nLR-pRBC were characterized by higher concentrations of free short and medium-chain fatty acids, carboxylic acids (pyruvate, lactate), and amino acids (arginine, cystine). The LR-pRBC had higher concentrations of glycolytic metabolites, high energy phosphate compounds (adenosine triphosphate [ATP]), and antioxidant metabolites (pentose phosphate, total glutathione).
CONCLUSION AND CLINICAL IMPORTANCE
Leukoreduction decreases the metabolic SLs of canine pRBC by preserving energy metabolism and preventing oxidative lesions.
Topics: Dogs; Animals; Blood Preservation; Erythrocytes; Leukocyte Reduction Procedures; Refrigeration; Phenotype
PubMed: 38553798
DOI: 10.1111/jvim.17031 -
Medicine Mar 2024In this study, we aimed to investigate the perioperative complications of the patients who underwent scoliosis surgery in our hospital and the factors that may affect...
In this study, we aimed to investigate the perioperative complications of the patients who underwent scoliosis surgery in our hospital and the factors that may affect the outcome. Between 2014 and 2018, scoliosis patients recorded data was examined retrospectively. Age, gender, height, body weight, comorbidity, Cobb index, scoliosis etiology, operation time, preoperative and postoperative hemoglobin, hematocrit, leukocyte, blood urea nitrogen, creatinine, coagulation value, operation time, level of instrumentation, intraoperative and postoperative blood loss, blood transfusion, intraoperative fluid administration, preoperative pulmonary function test values, blood gas values, urine outputs, hospital (LOS) and post anesthesia care unit stays, complications and mortality rates were examined. The files of 77 patients (48 female, 29 male) were retrospectively analyzed. The average age was 19.54 ± 16.32 years and 98.7% were elective surgery. The mean of LOS was 13.55 ± 9.13 days. As the preoperative hematocrit value decreases, LOS increases significantly. In patients with chronic obstructive pulmonary disease, smokers and high ASA scores, LOS is prolonged in patients with previous operations. As intraoperative colloid administration increased, crystalloid and blood products increased, it was also observed that the amount of crystalloid increased LOS. As the amount of intraoperative colloid or red blood cell administration increases, the duration of surgery and anesthesia increases, also increases the duration of post anesthesia care unit. Compared to patients with complications (n = 29) to the patients without complications (n = 47), it was found that they had longer anesthesia, and surgery times, also longer LOS times (P < .05). Our study showed that chronic obstructive pulmonary disease in the preoperative period, smoking, high ASA score, excessive use of colloid, prolonged duration of surgery and anesthesia, and long intubation durations increase the length of hospital stay. Preoperative comorbidity is directly related to postoperative complications and causes longer hospitalization after reconstructive scoliosis surgery.
Topics: Humans; Male; Female; Child, Preschool; Child; Adolescent; Young Adult; Adult; Retrospective Studies; Scoliosis; Pulmonary Disease, Chronic Obstructive; Postoperative Complications; Crystalloid Solutions; Length of Stay; Colloids
PubMed: 38552046
DOI: 10.1097/MD.0000000000037529 -
Acta Clinica Croatica Aug 2023The antibodies directed against human leukocyte antigen (HLA) molecules, which play a crucial role in allograft histocompatibility, are called anti-HLA antibodies....
The antibodies directed against human leukocyte antigen (HLA) molecules, which play a crucial role in allograft histocompatibility, are called anti-HLA antibodies. Anti-HLA antibodies against foreign HLA molecules may be present in patients with chronic kidney disease even before transplantation. The panel reactive antibody (PRA) test is used to measure the renal transplant candidate's immune sensitivity to HLA molecules other than their own HLA molecules by assessing the diversity of anti-HLA antibodies in the blood of these patients. This study aimed to determine the PRA values and the percentage of PRA positivity of Turkish male patients with chronic kidney disease (CKD), who had not been sensitized by the major known causes (those with no history of organ or tissue transplantation, those with no history of blood transfusion), who had not been diagnosed with any autoimmune diseases, and who had not been under immunosuppressive treatment. The study included 60 male patients aged over 18 years. All of the patients were followed up with a diagnosis of CKD at the Nephrology Clinic, Internal Medicine Department, Akdeniz University Medical Faculty Hospital. None of the patients included in the study was sensitized by a known mechanism previously (they did not have blood transfusion or organ transplantation). Glomerular filtration rate (GFR) levels of all patients were below the level of 60 mL/min/1.73 m. Patient data including their age information, etiology of CKD, accompanying diseases, and information about dialysis modalities were recorded. HLA antibody percentage was determined by the flow cytometry technique. Statistical data analysis was performed by using SPSS 22.0 (Statistical Package for Social Sciences, Version 22.0). The values of p less than 0.05 were considered statistically significant. Twenty patients were receiving dialysis treatment due to end-stage renal disease. Of the 60 patients included in the study, 25% showed PRA positivity; 28.3% of all study patients were found to be positive for anti-HLA class I antibodies and 26.7% of all study patients were found to be positive for anti-HLA class II antibodies on separate analysis for anti-HLA class I and anti-HLA class II antibody positivity. When the patients were categorized as PRA negative and PRA positive in two groups, there were no differences between the groups according to mean age, percentage of hemodialysis patients, percentage of peritoneal dialysis patients and presence of accompanying chronic diseases (such as hypertension, type 2 diabetes mellitus, hyperlipidemia, nephrolithiasis, coronary artery disease). In addition to this, evaluation of the GFR levels showed that the PRA positive group contained a significantly higher percentage of end-stage renal disease patients (GFR <15 mL/min/1.73 m) as compared with the PRA negative group. Detailed analysis of the percentages of PRA levels in the PRA positive patients, which was carried out to determine the degree of sensitization, showed that the PRA values were over 80% in 11.77% of the patients positive for anti-HLA class I antibodies. On the other hand, PRA values were within the range of 15%-80% in 88.23% of the patients who had anti-HLA class II antibodies. The PRA values were below 80% in all of the patients positive for anti-HLA class II antibodies and those positive for both anti-HLA class I and class II antibodies. In conclusion, PRA levels of the candidates for kidney transplantation should always be measured to assess their state of sensitization before transplantation, even though they have no risk factors known to cause anti-HLA antibody development.
Topics: Humans; Male; Adult; Middle Aged; Flow Cytometry; Diabetes Mellitus, Type 2; Antibodies; HLA Antigens; Kidney Failure, Chronic
PubMed: 38549598
DOI: 10.20471/acc.2023.62.02.02 -
Frontiers in Immunology 2024Unmodified donor lymphocyte infusions (DLI) after allogeneic stem cell transplantation (alloSCT) can boost the beneficial Graft-versus-Leukemia (GvL) effect but may also...
INTRODUCTION
Unmodified donor lymphocyte infusions (DLI) after allogeneic stem cell transplantation (alloSCT) can boost the beneficial Graft-versus-Leukemia (GvL) effect but may also induce severe Graft-versus-Host-Disease (GvHD). To improve the balance between GvL and GvHD, it is crucial to identify factors that influence the alloreactivity of DLI.
METHODS
We investigated the effects of the presence of patient-derived antigen-presenting cells at time of DLI as estimated by the bone marrow (BM) chimerism status, lymphopenia as measured by the absolute lymphocyte count (ALC) at time of DLI, and the presence of a viral infection ( or reactivation) close to DLI on the risk of GvHD after DLI. The cohort consisted of patients with acute leukemia or myelodysplastic syndrome who prophylactically or pre-emptively received DLI as standard care after alemtuzumab-based alloSCT. In patients at high risk for relapse, DLI was administered at 3 months after alloSCT (n=88) with a dose of 0.3x10 or 0.15x10 T cells/kg in case of a related or unrelated donor, respectively. All other patients (n=76) received 3x10 or 1.5x10 T cells/kg, respectively, at 6 months after alloSCT.
RESULTS
For both DLIs, patients with reduced-intensity conditioning and an unrelated donor had the highest risk of GvHD. For DLI given at three months, viral infection within 1 week before and 2 weeks after DLI was an additional significant risk factor (hazard ratio (HR) 3.66 compared to no viral infection) for GvHD. At six months after alloSCT, viral infections were rare and not associated with GvHD. In contrast, mixed BM chimerism (HR 3.63 for ≥5% mixed chimerism compared to full donor) was an important risk factor for GvHD after DLI given at six months after alloSCT. ALC of <1000x10/l showed a trend for association with GvHD after this DLI (HR 2.05 compared to ≥1000x106/l, 95% confidence interval 0.94-4.45). Furthermore, the data suggested that the presence of a viral infection close to the DLI at three months or ≥5% mixed chimerism at time of the DLI at six months correlated with the severity of GvHD, thereby increasing their negative impact on the current GvHD-relapse-free survival.
CONCLUSION
These data demonstrate that the risk factors for GvHD after DLI depend on the setting of the DLI.
Topics: Humans; T-Lymphocytes; Lymphocyte Transfusion; Hematopoietic Stem Cell Transplantation; Graft vs Host Disease; Leukemia, Myeloid, Acute; Unrelated Donors; Virus Diseases
PubMed: 38545096
DOI: 10.3389/fimmu.2024.1335341 -
International Journal of Molecular... Mar 2024Raman spectroscopy is a molecular spectroscopic technique able to provide detailed information about the chemical structure, phase, crystallinity, and molecular... (Review)
Review
Raman spectroscopy is a molecular spectroscopic technique able to provide detailed information about the chemical structure, phase, crystallinity, and molecular interactions of virtually any analyzed sample. Although its medical applications have been studied for several decades, only recent advances in microscopy, lasers, detectors, and better understanding of the principles of the Raman effect have successfully expanded its applicability to clinical settings. The promise of a rapid, label-free diagnostic method able to evaluate the metabolic status of a cell in vivo makes Raman spectroscopy particularly attractive for hematology and oncology. Here, we review widely studied hematological applications of Raman spectroscopy such as leukocyte activation status, evaluation of treatment response, and differentiation between cancer and non-malignant cells, as well as its use in still unexplored areas in hematology. We also discuss limitations and challenges faced by Raman spectroscopy-based diagnostics as well as recent advances and modifications of the method aimed to increase its applicability to clinical hematooncology.
Topics: Humans; Spectrum Analysis, Raman; Neoplasms; Antigen Presentation; Head; Hematology
PubMed: 38542349
DOI: 10.3390/ijms25063376 -
The Effect of Leukocyte Removal and Matrix Metalloproteinase Inhibition on Platelet Storage Lesions.Cells Mar 2024The reasons for unfavorable changes in platelet concentrate (PC) quality during storage are not fully understood yet. We aimed to evaluate whether leukocytes and matrix...
The reasons for unfavorable changes in platelet concentrate (PC) quality during storage are not fully understood yet. We aimed to evaluate whether leukocytes and matrix metalloproteinases (MMPs) lead to a decrease in the quality of PCs and examine whether MMP inhibition will slow down the platelets' aging. Nine PCs were divided into three parts: (1) leukocyte-depleted (F) PCs, (2) PCs with no additional procedures (NF), and (3) PCs with the addition of an MMP inhibitor-doxycycline (D). Each PC was stored for 144 h, and a sample for testing was separated from each part on the day of preparation and after 24, 48, 72 and 144 h of storage. Blood morphological analysis, platelet aggregation, and the expression of activation markers were evaluated. MMP-2 and MMP-9 concentration, activity, and gene expression were assessed. Platelet aggregation decreased, and platelet activation marker expression increased during the storage. D concentrates showed the lowest level of platelet activation. In turn, leukocyte-depleted PCs showed the highest level of platelet activation in general. MMP-9 platelet activity was higher in leukocyte-containing concentrates at the end of the storage period. We concluded that the filtration process leads to a higher platelet activation level. The presence of doxycycline in PCs reduces the expression of the activation markers as compared to leukocyte-depleted concentrates.
Topics: Matrix Metalloproteinase 9; Doxycycline; Blood Platelets; Platelet Activation; Leukocytes
PubMed: 38534349
DOI: 10.3390/cells13060506 -
BMC Pediatrics Mar 2024There are emerging clinical evidence for umbilical cord blood mononuclear cells (UCBMNCs) intervention to improve preterm complications. The first critical step in cell...
BACKGROUND
There are emerging clinical evidence for umbilical cord blood mononuclear cells (UCBMNCs) intervention to improve preterm complications. The first critical step in cell therapy is to obtain high-quality cells. This retrospective study aimed to investigate the quantity and quality of UCBMNCs from very preterm infants (VPIs) for the purpose of autologous cell therapy in prevention and treatment of preterm complications.
METHODS
Very preterm infants (VPIs) born in Guangdong Women and Children Hospital from January 1, 2017, to December 8, 2022, from whom cord blood was successfully collected and separated for public or private banking, were enrolled. The UCBMNCs characters from route cord blood tests performed in cord blood bank, impact of perinatal factors on UCBMNCs, the relationship between UCBMNCs characteristics and preterm outcomes, and the correlation of UCBMNCs characteristics and peripheral blood cells in VPIs were analyzed.
RESULTS
Totally, 89 VPIs underwent UCB collection and processing successfully. The median cell number post processing was 2.6 × 10. To infuse a dose of 5 × 10 cells/kg, only 3.4% of infants required a volume of more than 20 mL/kg, which exceeded the maximum safe volume limit for VPIs. However, when infusing 10 × 10 cells/kg, 25.8% of infants required a volume of more than 20 ml/kg volume. Antenatal glucocorticoids use and preeclampsia was associated with lower original UCBMNCs concentration. Both CD34+ hematopoietic stem cells (HSC) frequency and colony forming unit - granulocyte and macrophage (CFU-GM) number correlated negatively with gestational age (GA). UCBMNCs characters had no significant effect on preterm outcomes, whereas a significant positive correlation was observed between UCBMNCs concentration and total white blood cell, neutrophil, lymphocyte and PLT counts in peripheral blood.
CONCLUSION
UCBMNCs collected from VPIs was feasible for autologous cell therapy in improving preterm complications. Setting the infusion dose of 5 × 10 cells/kg guaranteed a safe infusion volume in more than 95% of the targeted infants. UCBMNCs characters did not affect preterm complications; however, the effect of UCBMNCs concentration on peripheral blood classification count should be considered when evaluating the immunomodulation of UCBMNCs transfusion.
Topics: Infant; Child; Humans; Infant, Newborn; Female; Pregnancy; Fetal Blood; Infant, Extremely Premature; Retrospective Studies; Leukocyte Count; Leukocytes, Mononuclear
PubMed: 38528484
DOI: 10.1186/s12887-024-04678-2