Search Results (37)

Immunotherapy is the standard first-line palliative treatment for metastatic melanoma; however, its role in myelodysplastic syndrome (MDS) remains uncertain. We report a case in which nivolumab, administered for metastatic melanoma, was associated with a marked improvement in concurrent treatment-related MDS. A 67-year-old man with a history of oligosecretory multiple myeloma developed transfusion-dependent MDS following autologous stem cell transplantation, requiring twice-weekly blood transfusions. He subsequently developed metastatic melanoma and was treated with single agent nivolumab to minimize treatment-related toxicity. Nivolumab effectively controlled the melanoma, and during treatment the patient experienced a durable hematologic response with sustained transfusion independence. At approximately two years of follow up, he remained transfusion-independent with stable peripheral blood counts, supporting the durability of the hematologic response. Although checkpoint inhibitors are not established therapies for therapy-related MDS and a causal relationship cannot be confirmed from a single case, the timing and sustained nature of the response are noteworthy. The patient experienced a significant improvement in quality of life with minimal adverse effects. This case adds to the limited literature on checkpoint inhibition in MDS and supports further investigation of its potential effects on hematologic recovery. Full article

Background: β-haemoglobinopathies, including sickle cell disease and transfusion-dependent β-thalassaemia, are among the most common monogenic disorders worldwide and represent a major global health burden. Conventional treatments, such as blood transfusions, iron chelation, fetal haemoglobin induction, and allogeneic haematopoietic stem cell transplantation, have improved outcomes but remain limited by treatment-related toxicity, donor availability, and incomplete curative potential. Methods: A narrative literature review was conducted using PubMed up to 2025. Search terms included “sickle cell disease,” “sickle cell anemia,” “β-thalassemia,” “transfusion-dependent beta-thalassemia,” “gene therapy,” “gene addition,” “gene editing,” “CRISPR-Cas9,” “lentiviral vector,” “children,” “paediatric,” and “pediatric.” Relevant clinical trials, reviews, consensus statements, and guidelines were selected and qualitatively analysed. Results: Gene therapy for β-haemoglobinopathies is based mainly on two strategies: gene addition and gene editing. Gene addition uses lentiviral vectors to introduce functional or modified β-globin genes into autologous haematopoietic stem cells, whereas gene editing targets regulatory pathways, particularly BCL11A, to reactivate fetal haemoglobin synthesis or correct disease-causing mutations. Clinical studies have shown encouraging outcomes, including transfusion independence in many patients with β-thalassaemia and marked reduction or elimination of vaso-occlusive crises in sickle cell disease. Paediatric and adolescent data are increasingly promising, although still limited. Conclusions: Gene therapy is reshaping the treatment landscape of β-haemoglobinopathies by offering a personalised and potentially curative approach. However, long-term safety, conditioning toxicity, fertility preservation, accessibility, costs, and implementation in high-prevalence regions remain critical challenges. Further studies are needed to optimise patient selection and expand equitable access. Full article

Sickle Cell Disease (SCD) is a pervasive monogenic disorder characterized by chronic hemolytic anemia, unpredictable vaso-occlusive crises, and progressive multi-organ damage, representing a significant global health burden. Driven by a point mutation in the β-globin gene, the resulting abnormal Hemoglobin S (HbS) polymerizes under deoxygenated conditions, leading to erythrocyte sickling and systemic endothelial dysfunction. While supportive therapies such as hydroxyurea and transfusions manage symptoms, the mandate for definitive curative therapies is urgent. Historically, allogeneic hematopoietic stem cell transplantation (HSCT) utilizing matched sibling donors (MSD) has been the sole curative option, offering high survival rates but constrained by limited donor availability and the risk of graft-versus-host disease (GVHD). Consequently, alternative donor sources, including matched unrelated donors, umbilical cord blood, and haploidentical donors, have expanded patient access, particularly with the integration of post-transplant cyclophosphamide (PTCy) to mitigate alloreactivity. Concurrently, the advent of autologous gene therapy, encompassing lentiviral gene addition (Lyfgenia) and CRISPR-Cas9 gene editing (Casgevy) offers a revolutionary donor-independent approach that eliminates GVHD risk. Lyfgenia employs a lentiviral vector to introduce an anti-sickling βT87Q hemoglobin variant into autologous hematopoietic stem cells, while Casgevy employs CRISPR-Cas9 to disrupt the erythroid-specific enhancer of the BCL11A transcription factor, derepressing γ-globin expression and elevating fetal hemoglobin. This review synthesizes the pathophysiological mechanisms of SCD, evaluates the clinical outcomes and limitations of both allogeneic HSCT and autologous gene therapies, and outlines the clinical decision-making paradigms and future innovations required to achieve equitable global access to these transformative treatments. Full article

Thalassemia is an inherited hemoglobin disorder characterized by chronic hemolytic anemia and substantial long-term healthcare needs. In β-thalassemia major, patients typically require regular red blood cell transfusions with iron chelation to prevent transfusional iron overload. Although supportive care has markedly improved survival, it is associated with a high treatment burden and does not provide a cure. In recent years, curative and disease-modifying therapies have expanded the treatment landscape. Allogeneic hematopoietic stem cell transplantation (HSCT) offers a potentially curative option for selected patients, while autologous gene therapy and gene-editing approaches have shown the capacity to achieve transfusion independence in clinical studies. In parallel, pharmacologic advances—including luspatercept, a transforming growth factor-beta (TGF-β) ligand trap—have been shown to enhance erythropoiesis and reduce transfusion requirements, and emerging agents such as fetal hemoglobin inducers (e.g., thalidomide) and the oral pyruvate kinase activator mitapivat have demonstrated clinically meaningful hemoglobin improvements in selected populations. Adjunctive strategies, including antioxidants, are under investigation to mitigate oxidative stress, and applications of artificial intelligence are increasingly used to support screening, diagnosis, and longitudinal monitoring of iron overload. This review synthesizes recent advances in curative therapies, novel pharmacologic agents, supportive strategies, and AI-enabled tools and highlights priorities for future clinical development and implementation. Full article

Background/Objectives: Thalassemia is highly prevalent in Indonesia, and its treatment imposes a significant financial burden. To date, thalassemia management in Indonesia remains largely limited to supportive therapies. This report aims to present the monitoring of the first Indonesian pediatric thalassemia patient to undergo gene therapy. Methods: Medical summaries were gathered across multiple time points. The gene therapy process consisted of several phases: screening, apheresis and cell manufacturing, conditioning, cell infusion, and post-treatment follow-up. The therapy utilized autologous CD34+ hematopoietic stem and progenitor cells (HSPCs), which were genetically modified using a lentiviral vector carrying the beta-globin gene. The primary outcome of this study was transfusion independence, determined through serial assessments of hematological parameters over a six-month period following gene therapy. Results: A 15-year-old female had been diagnosed with thalassemia major at the age of five. DNA analysis revealed compound heterozygous mutations Hb Malay (codon 19, AAC^Asn > AGC^Ser) and IVS1-nt5 (G > C). She had been receiving regular blood transfusions every 3–4 weeks, and hemosiderosis was detected in the liver and pancreas. Given the patient’s age—over 10 years—hematopoietic stem cell transplantation carries increased risks, making gene therapy the most suitable curative option. During the six-month follow-up period after gene therapy, the patient remained transfusion-independent and experienced no complications. Conclusions: In selecting an appropriate curative therapy for thalassemia patients, several factors must be considered. The successful implementation of the first gene therapy in an Indonesian pediatric thalassemia patient should serve as a catalyst for the continued development and expansion of curative treatment options for thalassemia patients across the country. Full article

Intraoperative cell salvage (ICS) is a blood conservation technique utilized in major surgery, yet its application in oncologic procedures remains debated. Concerns persist about the theoretical risk of metastasis through reinfusion of tumor cells, despite the established disadvantages of allogeneic blood transfusion (ABT), such as transfusion-related reactions and immunosuppression. In this review, we discuss the historical development of ICS, the technical processes of ICS including leukocyte depletion filtration and irradiation, and experimental and clinical data regarding its safety and efficacy. In vitro studies suggest that tumor cells undergo significant structural alterations during ICS processing, and additional filtration further reduces cell load, although complete removal is not always achieved. Observational studies of predominantly moderate quality, aggregated in multiple systematic reviews, consistently report no increased recurrence rates or reduced disease-free and overall survival in patients receiving ICS. Accordingly, national and international guidelines endorse the use of ICS during oncologic surgery. Although high-quality data—preferably from randomized controlled trials—are lacking, and certainty of available evidence from observational studies is low, ICS appears to be effective and safe. The broader adoption of its use during oncologic surgery may be warranted to minimize reliance on ABT and its associated risks. Full article

The Ross procedure introduced a new technique for aortic valve replacement by utilizing a pulmonary autograft to replace the diseased aortic valve. This approach provides a living, dynamic valve substitute capable of growth and adaptation to systemic pressures while addressing the limitations of mechanical valves, which require lifelong anticoagulation, and bioprosthetic valves, which lack durability and growth potential. The Ross procedure offers superior hemodynamic performance and freedom from anticoagulation. While initially popular, utilization declined due to its technical complexity and concerns regarding the potential for the failure of two valves, requiring additional operations. Advances in surgical techniques, such as reinforced autografts, improved myocardial protection, and better homograft preservation, coupled with evidence of favorable long-term outcomes, have renewed interest in the procedure. Preoperative imaging with echocardiography, cardiac magnetic resonance imaging, and computed tomography angiography ensures optimal patient selection and preparation. Intraoperatively, precise autograft harvesting, accurate implantation, and meticulous right ventricular outflow tract reconstruction are critical for success. Blood conservation techniques, such as acute normovolemic hemodilution and retrograde autologous priming, are employed to minimize transfusion-related complications. The anesthesiologist plays a critical role, including meticulous monitoring of myocardial function and hemodynamics, with intraoperative transesophageal echocardiography being essential for assessing valve integrity and ventricular function. Recent studies suggest that the Ross procedure can restore life expectancy in appropriately selected patients, reinforcing its value as a surgical option for managing aortic valve disease. Full article

Background: Autologous blood donation for placental malposition is common in Japan, but no studies have scientifically evaluated its usefulness. The purpose of this study was to evaluate the necessity for autologous blood donation for placental malposition. Methods: A retrospective study was conducted of patients who underwent autologous blood donation for placental malposition at Kindai University Hospital from 2012 to 2022. The primary outcome was the proportion of patients who were able to avoid allogeneic blood transfusion by autologous blood transfusion; secondary outcomes were autologous blood disposal rate, allogeneic blood transfusion rate, and complications of autologous blood donation and allogeneic blood transfusion. A systematic review of studies on autologous blood transfusion for placental malposition was conducted on PubMed. Results: Fifty-two patients (total placenta previa 16; marginal placenta previa 20; low-lying placenta 16) were included. Eight (15%) had complications at the time of autologous blood donation, including non-reassuring fetal heart rate, but no sequelae. Allogeneic blood transfusion was avoided by autologous blood transfusion in only five cases (9.6%). Autologous blood was discarded in nine cases (17%), seven of which had a low-lying placenta positioned normally at delivery. Allogeneic blood transfusion was performed in eight cases (15%) with no complications. In the systematic review, seven articles that met the inclusion criteria were selected for further evaluation. The results showed that there were no publications that scientifically demonstrated the benefit of autologous blood transfusion. Conclusions: The results of this study indicate that autologous blood donation for placental malposition has little benefit. Full article

Background: Individuals undergoing cardiac surgery face an increased risk of bleeding, as well as alterations in biochemical and coagulation patterns. Therefore, assessing the effectiveness of systems such as Cell Salvage is necessary to prevent potential surgical complications. Objective: To evaluate the efficacy of Cell Salvage in relation to the biochemical parameters of the red blood series and coagulation, as well as the risk of hemorrhage. Methods: A systematic review, accompanied by a meta-analysis, was executed via an extensive literature exploration encompassing Medline, CINAHL, Scopus, Web of Science, and the Cochrane Library. The inclusion criteria comprised studies in English or Spanish, without year restrictions, conducted in adults and with a randomized controlled trial design. Results: Twenty-six studies were included in the systematic review, involving a total of 2850 patients (experimental group = 1415; control group = 1435). Cell Salvage did not demonstrate superior outcomes compared to allogeneic transfusions in the management of post-surgical hemorrhage, as well as in total blood loss, platelet count, fresh frozen plasma, and fibrinogen. However, Cell Salvage showed a greater effectiveness for hemoglobin (moderate evidence), hematocrit (low evidence), post intervention D-dimer (low evidence), and some coagulation-related parameters (low evidence) compared to allogeneic transfusions. Finally, better results were found in the control group for INR parameters. Conclusions: The use of the Cell Salvage system holds high potential to improve the postoperative levels of biochemical and coagulation parameters. However, the results do not provide definitive evidence regarding its effectiveness for hemorrhage control, platelet count, fresh frozen plasma, and fibrinogen. Therefore, it is recommended to increase the number of studies to assess the impact of the Cell Salvage system on improvements in the red blood cell count and patient coagulation patterns. In addition, protocols should be homogenized, and variables such as the sex of the participants should be taken into account. Full article

Casgevy (exa-cel) is an autologous cellular therapy modified ex vivo by a CRISPR-Cas9-mediated gene-editing technology. For Casgevy to be granted the indication in transfusion-dependent β-thalassemia, one single-arm trial was submitted which was not amenable to conventional statistical analysis of ‘effect of cause’. Therefore, an analysis was conducted on the basis of ‘cause of effect’ making use of the scheme described by Toulmin coupled to an analysis of causal inference. Based on the current data within the submitted study: subjects with transfusion-dependent β-thalassemia no longer needed a red blood cell transfusion with a 93-percent probability if and only if administered Casgevy; PNS = 93%. It is acknowledged that unknown elements of safety may yet be revealed by long-term follow-up of recipients of Casgevy. Its durability of efficacy is, at present, also an unknown that may also be ascertained by long-term follow-up of recipients. The limitations of a causal analysis are related to assumptions of the proposed causal structure which may not capture the complexity of the real world. Overall, the claim that Casgevy is indicated to treat people with transfusion-dependent β-thalassemia is considered to be supported by the results of the submitted study; the benefit–risk evaluation of Casgevy is found to be positive. Full article

Epidemiological data suggest that moderate hyperoxemia may be associated with an improved outcome after traumatic brain injury. In a prospective, randomized investigation of long-term, resuscitated acute subdural hematoma plus hemorrhagic shock (ASDH + HS) in 14 adult, human-sized pigs, targeted hyperoxemia (200 < P_aO₂ < 250 mmHg vs. normoxemia 80 < P_aO₂ < 120 mmHg) coincided with improved neurological function. Since brain perfusion, oxygenation and metabolism did not differ, this post hoc study analyzed the available material for the effects of targeted hyperoxemia on cerebral tissue markers of oxidative/nitrosative stress (nitrotyrosine expression), blood–brain barrier integrity (extravascular albumin accumulation) and fluid homeostasis (oxytocin, its receptor and the H₂S-producing enzymes cystathionine-β-synthase and cystathionine-γ-lyase). After 2 h of ASDH + HS (0.1 mL/kgBW autologous blood injected into the subdural space and passive removal of 30% of the blood volume), animals were resuscitated for up to 53 h by re-transfusion of shed blood, noradrenaline infusion to maintain cerebral perfusion pressure at baseline levels and hyper-/normoxemia during the first 24 h. Immediate postmortem, bi-hemispheric (i.e., blood-injected and contra-lateral) prefrontal cortex specimens from the base of the sulci underwent immunohistochemistry (% positive tissue staining) analysis of oxidative/nitrosative stress, blood–brain barrier integrity and fluid homeostasis. None of these tissue markers explained any differences in hyperoxemia-related neurological function. Likewise, hyperoxemia exerted no deleterious effects. Full article

Objectives: It has been shown that concomitant autologous blood and dextranomer/hyaluronic acid (Deflux^®) injection, hydrodistension autologous blood injection technique (HABIT), had a better mound preservation and treatment success compared to the hydrodistension injection technique (HIT) in vesicoureteral reflux (VUR) correction. In this study, we aimed to show microscopically whether the concomitant injection of autologous blood decreases the leakage of Deflux^® particles. Methods: Children with VUR who underwent HIT or HABIT between March 2020 and January 2023 were enrolled. Following the completion of the procedure on each ureter, the bladder was irrigated for 3 to 5 min, and the retrieved sample of irrigation fluid was evaluated for dextranomer particle count as “immediate leakage”. A Foley catheter was placed, and a urine sample after 12 h was collected as “early leakage”. Results: A total of 86 children with a median age of 3.0 years (interquartile range = 4.6) were included. Overall, 66 patients underwent HABIT, and 20 children underwent HIT. Rupture was observed in five patients during the procedure, and re-injection was conducted successfully in these cases. Immediate, early, and total particle leakage in the first 12 h of the injection were significantly less in the HABIT group compared to the HIT group. In the regression analysis, only the injection technique (HIT/HABIT) and rupture were significantly associated with the total particle leakage in the first 12 h. Conclusions: Immediate injection of autologous blood into the mound following an endoscopic correction of VUR in children is associated with significantly less Deflux^® particle leakage from the injection site regardless of the VUR grade. We hypothesize that a concomitant blood injection into the Deflux^® mound will create a blood clot while the needle is kept in situ and help to stabilize the mound and decrease treatment failure by minimizing particle leakage from the injection site. Full article

The prevalence of autologous blood transfusions (ABTs) presents a formidable challenge in maintaining fair competition in sports, as it significantly enhances hemoglobin mass and oxygen capacity. In recognizing ABT as a prohibited form of doping, the World Anti-Doping Agency (WADA) mandates stringent detection methodologies. While current methods effectively identify homologous erythrocyte transfusions, a critical gap persists in detecting autologous transfusions. The gold standard practice of longitudinally monitoring hematological markers exhibits promise but is encumbered by limitations. Despite its potential, instances of blood doping often go undetected due to the absence of definitive verification processes. Moreover, some cases remain unpenalized due to conservative athlete-sanctioning approaches. This gap underscores the imperative need for a more reliable and comprehensive detection method capable of unequivocally differentiating autologous transfusions, addressing the challenges faced in accurately identifying such prohibited practices. The development of an advanced detection methodology is crucial to uphold the integrity of anti-doping measures, effectively identifying and penalizing instances of autologous blood transfusion. This, in turn, safeguards the fairness and equality essential to competitive sports. Our review tackles this critical gap by harnessing the potential of microRNAs in ABT doping detection. We aim to summarize alterations in the total microRNA profiles of erythrocyte concentrates during storage and explore the viability of observing these changes post-transfusion. This innovative approach opens avenues for anti-doping technologies and commercialization, positioning it as a cornerstone in the ongoing fight against doping in sports and beyond. The significance of developing a robust detection method cannot be overstated, as it ensures the credibility of anti-doping efforts and promotes a level playing field for all athletes. Full article

Background: Pathological changes associated with spinal cord injury (SCI) can be observed distant, rostral, or caudal to the epicenter of injury. These remote areas represent important therapeutic targets for post-traumatic spinal cord repair. The present study aimed to investigate the following in relation to SCI: distant changes in the spinal cord, peripheral nerve, and muscles. Methods: The changes in the spinal cord, the tibial nerve, and the hind limb muscles were evaluated in control SCI animals and after intravenous infusion of autologous leucoconcentrate enriched with genes encoding neuroprotective factors (VEGF, GDNF, and NCAM), which previously demonstrated a positive effect on post-traumatic restoration. Results: Two months after thoracic contusion in the treated mini pigs, a positive remodeling of the macro- and microglial cells, expression of PSD95 and Chat in the lumbar spinal cord, and preservation of the number and morphological characteristics of the myelinated fibers in the tibial nerve were observed and were aligned with hind limb motor recovery and reduced soleus muscle atrophy. Conclusion: Here, we show the positive effect of autologous genetically enriched leucoconcentrate-producing recombinant neuroprotective factors on targets distant to the primary lesion site in mini pigs with SCI. These findings open new perspectives for the therapy of SCI. Full article

In animals, invasive pulmonary artery thermodilution (PATD) is a gold standard for cardiac output (CO) monitoring, but it is impractical in clinical settings. This study evaluates the agreement between PATD and noninvasive electrical cardiometry (EC) for measuring CO and analyzes the other EC-derived hemodynamic variables in six healthy anesthetized dogs subjected to four different hemodynamic events in a sequential order: (1) euvolemia (baseline); (2) hemorrhage (33% blood volume loss); (3) autologous blood transfusion; and (4) 20 mL/kg colloid bolus. The CO measurements obtained using PATD and EC are compared using Bland–Altman analysis, Lin’s concordance correlation (LCC), and polar plot analysis. Values of p < 0.05 are considered significant. The EC measurements consistently underpredict the CO values as compared with PATD, and the LCC is 0.65. The EC’s performance is better during hemorrhage, thus indicating its capability in detecting absolute hypovolemia in clinical settings. Even though the percentage error exhibited by EC is 49.4%, which is higher than the standard (<30%), EC displays a good trending ability. Additionally, the EC-derived variables display a significant correlation with the CO measured using PATD. Noninvasive EC may have a potential in monitoring trends in hemodynamics in clinical settings. Full article