Current Research in Translational Medicine最新文献

Umbilical cord blood (UCB) is an alternative source of stem cells for patients lacking a 9/10 or 10/10 HLA identical donor. However, after UCB transplantation, time to engraftment and immune recovery are prolonged, increasing the risk of fatal complications. Mesenchymal stromal cells (MSC) can support hematopoietic engraftment and have immunosuppressive effects.

The primary objective of this phase I/II multicenter study was to determine the feasibility and safety of UCB transplantation with co-infusion of third party MSC, as assessed by treatment related mortality (TRM) at day 100. Secondary objectives were engraftment, immune recovery, occurrence of graft versus host disease (GVHD), infections, disease free survival, relapse incidence and overall survival.

Eleven patients were grafted according to this protocol. Allogeneic transplantation after co-infusion appears feasible with 18 % TRM at day 100. Engraftment data show a median time of 16 days to neutrophil and 27 days to platelet recovery, which is shorter than what is usually reported after UCB transplantation. Only 1 episode of acute GVHD was reported.

In conclusion, MSC and UCB co-transplantation is feasible and might help overcome some of the drawbacks of UCB transplantation.

Background

: The setting of normovolemic anemia is required for a variety of research applications, such as testing of novel medication for anemia treatment. Unfortunately, large animal models using full blood draw and replenishment with balanced electrolyte solution (BES) lead to bleeding complications, as coagulation factors and platelets are also drawn. We therefore aimed to establish a model of selective red blood cell (RBC) depletion to the main endpoint of hemoglobin (Hgb) levels of 4–6 g dL⁻¹ using apheresis in sheep.

Methods

: In vitro experiments were performed first to establish the apheresis protocol. In vivo, anesthetized ewes underwent a sham protocol without apheresis (n = 5) or apheresis (n = 4). Both groups were observed for the following six hours at a defined starting point (BE0) to compare Hgb, hematocrit (Hct), coagulation and clinical parameters. For statistical analysis, unpaired t-test with Welch`s correction was used.

Results

: Hgb levels were effectively decreased by 51 % to mean Hgb of 4.4 g dL⁻¹ in the apheresis group compared to 9.1 g dL⁻¹ in sham (*p < 0.0001). Hct (11.2% vs 25.1 %, *p = 0.01) and RBCs (3.7 vs 8.2 × 10⁶/µl, *p = 0.003) also decreased. The relative number of platelets compared to baseline was different (55.6 ± 10.6% vs. 100 ± 0 %, *p = 0.004), but no hemorrhage was observed. White blood cells (WBCs), lactate, prothrombin ratio and activated partial thromboplastin time (aPTT) remained within similar ranges.

Conclusions

: Critical normovolemic anemia without bleeding complications was successfully reached by selective RBC depletion in sheep. Investigations of physiological adaptations to severe anemia and pharmaceutical testing can be performed in large animals with depleted RBCs.

In 2023, the EBMT Practice harmonization and Guidelines Committee partnered with the EBMT Infection Diseases Working Party (IDWP) to undertake the task of delivering best practice recommendations, aiming to harmonize by expert consensus, the already existing definitions and future epidemiological and clinical studies among centers of the EBMT network. To attain this objective, a group of experts in the field was convened. The workgroup identified and discussed some critical aspects in definitions of community-acquired respiratory viruses (CARV) and adenovirus (ADV) infections in recipient of hematopoietic cell transplant (HCT). The methodology involved literature review and expert consensus. For CARV, expert consensus focused on defining infection severity, infection duration, and establishing criteria for lower respiratory tract disease (LRTD). For ADV, the expert consensus focused on surveillance methods and the definitions of ADV infection, certainty levels of disease, response to treatment, and attributable mortality. This consensus workshop provided indications to EBMT community aimed at facilitating data collection and consistency in the EBMT registry for respiratory viral infectious complications.

Background

Fungal infections pose a significant threat to individuals with hematologic malignancies due to compromised immune systems. Dectin-1, a pivotal pattern recognition receptor, plays a central role in antifungal immune responses. Understanding its genetic variants' impact is crucial for advancing personalized therapeutic approaches.

Methods

Employing systematic review methods, studies were meticulously selected and assessed for relevance. Data extraction encompassed Dectin-1 genetic variants, antifungal immune responses, and disease outcomes.

Results

Findings unveiled a complex relationship between Dectin-1 genetic variants and antifungal immunity in hematologic malignancies. Variable associations emerged, influencing susceptibility to fungal infections and disease prognosis. Moreover, implications for treatment outcomes were explored, suggesting potential avenues for tailored interventions.

Conclusions

This systematic review underscores the need for further investigation into the precise influence of Dectin-1 genetic variants on antifungal immunity and disease progression in hematologic malignancies. Insights gained could pave the way for personalized therapeutic strategies, optimizing infection prevention and malignancy management. By delving into the intricate connections between genetic nuances, immune responses, and clinical trajectories, this review contributes to the ongoing discourse surrounding hematologic malignancies, fungal infections, and their multifaceted interplay.

Hemophagocytic lymphohistiocytosis (HLH) is an hyperinflammatory state resulting from increased secretion of proinflammatory cytokines, which are responsible for clinical, biological and cytological manifestations.

Objective

The aim of our study is to describe the epidemiological, clinical, biological, etiological and evolutionary profile of HLH in Tunisia.

Methods

A retrospective study that involved patients, with images of hemophagocytosis in myelograms analyzed at the laboratory of biological hematology of the University Hospital "Hédi-Chaker" of Sfax-Tunisia, followed at these departments: hematology, internal medicine, department of infectious-diseases and department of gastroenterology, (June2017- May2021). First, we identified all patients with hemophagocytosis images. Secondly, we selected the patients who fulfilled the diagnostic criteria of the HLH-2004-score.

Results

Nineteen patients were included in this study. Nine men and 10 women with a mean age of 37.95 years. Fever was present in all patients. Organomegaly was described in 74% of cases. The most frequent cytopenia was anemia (100%). Hypertriglyceridemia was noted in 79% of cases and hyperferritinemia (> 500 ng/mL) was ubiquitous. In myelogram, 68% of patients had slides showing numerous or very numerous images of hemophagocytosis. The infectious pathology was the most common cause of HLH (42%). No cause was found in 10% of cases. The corticosteroid therapy at a dose of 1 mg/kg/day was prescribed in 89% of our patients. The overall evolution was favorable in 58% of cases. The mortality was not associated with the causal pathology (p=0.218).

Conclusion

Secondary HLH is likely to be under-recognized, which contributes to its high morbidity and mortality. Early recognition is crucial for any reasonable attempt at curative therapy.

Hydrogels are commonly used as carriers for cell delivery due to their similarities to the extracellular matrix. A contraction-suppressed full-thickness wound model was used to evaluate the therapeutic potential of Pluronic F127 (PF127) hydrogel loaded with adipose-derived stromal vascular fraction (AdSVF), mesenchymal stem cells (AdMSC), and conditioned media (AdMSC-CM) for the repair of wounds in a rabbit model. The experimental study was conducted on forty-eight healthy adult New Zealand white rabbits randomly divided into eight groups with six animals each and treated with AdSVF, AdMSC, and AdMSC-CM as an injectable or topical preparation. The healing potential of different adipose-derived cell-based and cell-free therapeutics was evaluated based on percentage wound healing, period of epithelialization, epidermal thickness, scar evaluation, histopathology analysis, histochemical evaluation, immunohistochemistry (collagen type I), and hydroxyproline assay by comparing with the positive and negative control. Collagen density analysis using different staining methods, immunohistochemistry, and hydroxyproline assay consistently showed that delivering AdMSC and AdMSC-CM in PF127 hydrogel enhanced epithelialization, collagen production, and organization, contributing to improved tissue strength and quality. Even though allogeneic AdSVF was found to promote wound healing in rabbits, it has a lower potential than AdMSC and AdMSC-CM. The wound healing potential of AdMSC and AdMSC-CM was enhanced when loaded in PF127 hydrogel and applied topically. Even though wounds treated with AdMSC outperformed AdMSC-CM, a significant difference in the healing quality was not observed in most instances, indicating almost similar therapeutic potential. The findings indicate that the wound healing potential of AdMSC and AdMSC-CM was enhanced when loaded in PF127 hydrogel and applied topically. These treatments promoted collagen production, tissue organization, and epidermal regeneration, ultimately improving overall healing outcomes.

Sézary syndrome (SS) is a rare and aggressive T-cell lymphoma with a poor prognosis in advanced stages. Allogeneic hematopoietic cell transplantation (allo-HCT) offers a potential cure, but complications such as graft-versus-host disease (GvHD) remain a clinical challenge. Mogamulizumab, a humanized anti-CC chemokine receptor 4 (CCR4) antibody, is sometimes used as a bridge to transplantation, but its potential interactions with allo-HCT are unclear. This report describes the case of a 37-year-old man with advanced SS who received mogamulizumab therapy followed by allo-HCT from an HLA-identical sibling donor. The patient developed severe gastrointestinal acute GvHD, which was treated with steroids and infliximab. However, the condition rapidly progressed to severe intestinal symptoms and life-threatening haemorrhagic shock, ultimately resulting in the patient's death. This case highlights a potential link between mogamulizumab and severe acute GvHD promoted by drug-induced suppression of regulatory T cells. Further research is required to fully understand the interaction between mogamulizumab and allo-HCT and to determine whether it is an optimal approach as a bridge to transplant therapy. This paradigmatic case suggests the need of personalizing transplant strategies by selecting appropriate conditioning therapy and GvHD prophylaxis to minimize potential toxicity.