Stem Cell Transplantation Therapy Research Articles

Paediatric Acute Lymphoblastic Leukaemia: A Narrative Review of Current Knowledge and Advancements.

This review aims to provide an update on current knowledge regarding paediatric acute lymphoblastic leukaemia (ALL), focusing on recent advancements in diagnosis and treatment, as well as future directions in the field. ALL is the most frequently diagnosed paediatric malignancy, with advances leading to a 90% survival rate. The heterogeneity of childhood ALL requires a precise diagnostic algorithm incorporating morphological, immunophenotypic, and cytogenetic analyses. Research is exploring next-generation sequencing and artificial intelligence-aided techniques for future diagnostic approaches. Despite these advancements, global disparities in healthcare access hinder prompt diagnosis and management. The pathophysiology of ALL involves chromosomal and genetic alterations which disrupt cell-cycle regulation and result in uncontrolled lymphoblast proliferation. Environmental factors also contribute to leukaemogenesis. Risk-stratification based on genetic subtypes has significant implications for risk-based therapy. Chemotherapy is administered in three phases: induction, consolidation, and maintenance, with prophylactic intrathecal chemotherapy considered essential. For high-risk, refractory, or relapsed ALL, haematopoietic stem cell transplantation and novel therapies such as tyrosine kinase inhibitors, chimeric antigen receptor T-cell therapy, and blinatumomab immunotherapy, have improved outcomes. Ongoing clinical trials aim to further improve treatment efficacy, reduce toxicity, and increase survival. Although prevention strategies for ALL exist at three levels, the supporting evidence remains limited, highlighting a need for further research. Continued research and clinical trials are essential to addressing the gaps treatment efficacy and prevention strategies. Efforts to improve global healthcare access and integrate novel diagnostic and therapeutic approaches are crucial for advancing outcomes for paediatric patients with ALL.

Otorhinolaryngological Problems in Mucopolysaccharidoses: A Review of Common Symptoms in a Rare Disease

Background: The mucopolysaccharidoses (MPSs) are very rare lysosomal diseases. MPSs belong to inherited diseases; however, newborns are usually asymptomatic. A deficiency of one of the enzymes, which is responsible for glycosaminoglycan (GAG) catabolism, results in the accumulation of this material. GAGs lead to progressive damage to tissues. More than 90% of patients with MPS suffer from otitis media with effusion or recurrent otitis media, craniofacial dysmorphia, obstructive sleep apnea, different types of hearing loss, and progressive upper and lower airway dysfunction. Patients visit otolaryngologists often before the diagnosis of MPS. Thus, the awareness of symptoms of MPS is crucial for otolaryngologists and pediatricians. The earlier the diagnosis is made, the more effective treatment is. Ineffective or delayed treatment leads to premature death. Two principal treatments for MPS are currently available: hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT). In recent years, there has been a growing interest in gene therapy as a potential treatment for patients with MPS. Mortality in patients with MPS typically occurs during childhood and early adolescence as a consequence of upper and lower respiratory diseases. Methods: This systematic review is based on papers available in the following scientific databases: MEDLINE (via PubMed), Web of Science, Scopus, and the Cochrane Library. Results: After screening, 72 articles met our inclusion criteria. Conclusions: It is of paramount importance that otolaryngologists are involved in this field. This narrative review examines and synthesizes the otolaryngologic issues encountered in patients with MPS.

Stem cell research and improving cancer treatments

Stem cell research has emerged as a pivotal area in oncology, offering innovative approaches to cancer treatment. This research explores the potential of stem cells to enhance therapeutic outcomes in various cancer types. To evaluate the role of stem cells in cancer treatment, focusing on their ability to differentiate into specialized cell types, promote tissue regeneration, and deliver targeted therapies. A comprehensive review of current literature was conducted, analyzing studies that investigate the application of stem cells in hematological malignancies and solid tumors. Key methodologies included in vitro experiments, animal models, and clinical trials assessing stem cell therapies, including hematopoietic stem cell transplantation and mesenchymal stem cell-based therapies. Findings indicate that stem cells can improve treatment efficacy by facilitating tumor regression, enhancing immune responses, and reducing treatment-related toxicity. Notably, mesenchymal stem cells have shown promise in delivering therapeutic agents directly to tumors and modulating the tumor microenvironment. Stem cell research holds significant potential to revolutionize cancer treatment strategies. Continued exploration of stem cell applications may lead to more effective, personalized therapies, ultimately improving patient outcomes in various cancer types. Further clinical trials are necessary to establish standardized protocols and assess long term effects.

Pathophysiology of Congenital High Production of IgE and Its Consequences: A Narrative Review Uncovering a Neglected Setting of Disorders.

Elevated serum IgE levels serve as a critical marker for uncovering hidden immunological disorders, particularly inborn errors of immunity (IEIs), which are often misdiagnosed as common allergic conditions. IgE, while typically associated with allergic diseases, plays a significant role in immune defense, especially against parasitic infections. However, extremely high levels of IgE can indicate more severe conditions, such as Hyper-IgE syndromes (HIES) and disorders with similar features, including Omenn syndrome, Wiskott-Aldrich syndrome, and IPEX syndrome. Novel insights into the genetic mutations responsible for these conditions highlight their impact on immune regulation and the resulting clinical features, including recurrent infections, eczema, and elevated IgE. This narrative review uniquely integrates recent advances in the genetic understanding of IEIs and discusses how these findings impact both diagnosis and treatment. Additionally, emerging therapeutic strategies, such as hematopoietic stem cell transplantation (HSCT) and gene therapies, are explored, underscoring the potential for personalized treatment approaches. Emphasizing the need for precise diagnosis and tailored interventions aims to enhance patient outcomes and improve the quality of care for those with elevated IgE levels and associated immunological disorders.

Hematopoietic stem cell transplantation therapy for refractory' Crohn disease: A systematic review and meta-analysis.

Despite the availability of numerous treatments for Crohn disease, there are patients who do not respond to any therapy, thereby diminishing their quality of life. The aim of this review is to analyze the efficacy and safety of autologous hematopoietic stem cell transplantation therapy for refractory Crohn disease. This work is a systematic review with meta-analysis conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analyses. Electronic databases such as PubMed, Scopus, Web of Science, and ClinicalTrials were consulted. The searches were carried out in August 2024. To evaluate the efficacy of autologous hematopoietic stem cell transplantation in inducing remission, the mean and standard deviation of the Crohn's Disease Activity Index pre- and post- treatment were used, and a fixed-effects meta-analysis was conducted. Additionally, to assess the efficacy in perianal fistulas, a random-effects meta-analysis was performed, collecting data on the number of subjects with fistulas at the beginning and end of the intervention. All 95% confidence intervals were calculated, and the I2 statistic was used to assess the heterogeneity of the outcome variables. A total of 609 records were identified from databases, with 12 studies selected for inclusion in the review. Immediate intervention proved effective in inducing a decrease in the Crohn Disease Activity Index compared to late intervention with conventional therapies. Moreover, the meta-analysis demonstrated efficacy for Crohn disease and associated fistulas with a mean decrease in the CDAI of -217.53 ± 14.3. When evaluating the efficacy of the procedure in perianal fistulas, a risk ratio of 0.47 with a 95% CI of [0.26, 0.86] was obtained. However, the procedure showed adverse effects, such as infections, acute renal failure or deaths. Systemic autologous hematopoietic stem cell transplantation has shown efficacy in patients who fail to achieve remission of their Crohn disease with conventional therapies. This procedure has also demonstrated efficacy in treating perianal fistulas. However, it is essential to carefully evaluate de implementation of this procedure due to the associated risks.

Phase I study of safety and efficacy of allogeneic natural killer cell therapy in relapsed/refractory neuroblastomas post autologous hematopoietic stem cell transplantation

Despite low incidence, neuroblastoma, an immunologically cold tumor, is the most common extracranial solid neoplasm in pediatrics. In relapsed/refractory cases, the benefits of autologous hematopoietic stem cell transplantation (auto-HSCT) and other therapies are limited. Natural killer (NK) cells apply cytotoxicity against tumor cells independently of antigen-presenting cells and the adaptive immune system. The primary endpoint of this trial was to assess the safety of the injection of allogenic, ex vivo-expanded and primed NK cells in relapsed/refractory neuroblastoma patients after auto-HSCT. The secondary endpoint included the efficacy of this intervention in controlling tumors. NK cells were isolated and primed ex vivo (by adding interleukin [IL]-2, IL-15, and IL-21) in a GMP-compliant CliniMACS system and administered to four patients with relapsed/refractory MYCN-positive neuroblastoma. NK cell injections (1 and 5 × 107 cells/kg in the first and second injections, respectively) were safe, and no acute or sub-acute adverse events were observed. During the follow-up period, one complete response (CR) and one partial response (PR) were observed, while two cases exhibited progressive disease (PD). In follow-up evaluations, two died due to disease progression, including the case with a PR. The patient with CR had regular growth at the 31-month follow-up, and another patient with PD is still alive and receiving chemotherapies 20 months after therapy. This therapy is an appealing and feasible approach for managing refractory neuroblastomas post-HSCT. Further studies are needed to explore its efficacy with higher doses and more frequent administrations for high-risk neuroblastomas and other immunologically cold tumors.Trial registration number: irct.behdasht.gov.ir (Iranian Registry of Clinical Trials, No. IRCT20201202049568N1).

A global perspective of the changing epidemiology of invasive fungal disease and real-world experience with the use of isavuconazole.

Global epidemiological data show that the incidence of invasive fungal disease (IFD) has increased in recent decades, with the rising frequency of infections caused by Aspergillus and Mucorales order species. The number and variety of patients at risk of IFD has also expanded, owing in part to advances in the treatment of hematologic malignancies and other serious diseases, including hematopoietic stem cell transplantation (HCT) and other therapies causing immune suppression. Isavuconazonium sulfate (active moiety: isavuconazole) is an advanced-generation triazole antifungal approved for the treatment of invasive aspergillosis and mucormycosis that has demonstrated activity against a variety of yeasts, moulds, and dimorphic fungi. While real-world clinical experience with isavuconazole is sparse in some geographic regions, it has been shown to be effective and well tolerated in diverse patient populations, including those with multiple comorbidities who may have failed to respond to prior triazole antifungal therapy. Isavuconazole may be suitable for patients with IFD receiving concurrent QTc-prolonging therapy, as well as those on venetoclax or ruxolitinib. Data from clinical trials are not available to support the use of isavuconazole prophylactically for the prevention of IFD or for the treatment of endemic IFD, such as those caused by Histoplasma spp., but real-world evidence from case studies suggests that it has clinical utility in these settings. Isavuconazole is an option for patients at risk of IFD, particularly when the use of alternative antifungal therapies is not possible because of toxicities, pharmacokinetics, or drug interactions.

Thrombotic complications after hematopoietic stem cell transplantation and other cellular therapies

Hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor-T (CAR-T) immunotherapy are widely used for the management of hematological malignancies. HSCT can be complicated by endothelial injury syndromes, such as HSCT-thrombotic microangiopathy (HSCT-TMA) and sinusoidal obstructive syndrome/veno-occlusive disease (SOS/VOD), which are life-threatening. Moreover, venous thromboembolic events (VTEs) are common in HSCT recipients due to endothelial injury, use of central venous catheters, prolonged hospitalization, and the development of a procoagulant state. VTEs have also been reported post-CAR-T infusion. The management of thrombotic events in these patients is challenging, due to the high risk of bleeding that is present. CAR-T immunotherapy might be followed by toxicities, such as cytokine release syndrome (CRS) and immune effector cell-associated neuro-toxicity syndrome (ICANS). Endothelial dysfunction is implicated in the pathogenesis of these syndromes. Early recognition and management of the above complications are crucial for better patient outcomes.

Hematopoietic stem cell transplantation leads to biochemical and functional correction in two mouse models of acid ceramidase deficiency

Farber disease (FD) and spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) are ultra-rare lysosomal storage disorders caused by deficient acid ceramidase (ACDase) activity. Although both conditions are caused by mutations in the ASAH1 gene, clinical presentations differ considerably. FD patients usually die in childhood while SMA-PME patients can live until adulthood. There is no treatment for FD or SMA-PME. Hematopoietic stem cell transplantation (HSCT) and gene therapy strategies for the treatment of ACDase deficiency are being investigated. We have previously generated and characterized mouse models of both FD and SMA-PME that recapitulate the symptoms described in patients. Here, we show that HSCT improves lifespan, behavior, hematopoietic system anomalies, plasma cytokine levels, and significantly reduces histiocytic infiltration and ceramide accumulation throughout the tissues investigated, including the CNS, in both models of ACDase deficient mice. HSCT was also successful in preventing lesion development and significant demyelination of the spinal cord seen in SMA-PME mice. Importantly, we note that only early and generally pre-symptomatic treatment was effective and kidney impairment was not improved in either model.

Allogeneic Hematopoietic Cell Transplantation for Myelofibrosis Aged 70 Years or Older: A Study from the German Registry for Stem Cell Transplantation

Current consensus recommends hematopoietic cell transplantation (HCT) for patients with myelofibrosis with intermediate or high-risk disease and age of less than 70 years. However, a higher chronological age should not be prohibitive for the eligibility decision in general, acknowledging that current life expectancy for the general population aged 70 years is ∼15 years, and current numbers of patients transplanted at 70 years or older is steadily increasing. The following study aimed to evaluate characteristics and outcomes of HCT in 115 myelofibrosis patients aged 70 years or older. This is a retrospective multicenter study, using the German Registry for Stem Cell Transplantation and Cellular Therapy (DRST). Adult myelofibrosis patients were included who received HCT up until 2021. Patients with secondary leukemia were excluded. Main endpoints were HCT demographics over time and outcomes after HCT (including overall survival, relapse incidence, non-relapse mortality, and graft-versus-host disease/relapse-free survival). Numbers of HCT increased over the past decade, with a significant spike since 2019. Comorbidity status of transplanted patients improved over time, while reduced-intensity conditioning was the preferred HCT platform, especially in most recent years. The 3-year overall survival was 55% (95% confidence interval [CI], 44%-65%). The 1-year cumulative incidence of relapse was 7% (95% CI, 3%-13%) and the 1-year cumulative incidence of non-relapse mortality was 22% (95% CI, 14%-31%). The 3-year graft-versus-host disease and relapse-free survival was 37% (95% CI, 27%-47%). Driver mutation genotype (in particular, non-CALR/MPL genotype) appeared to be the only variable that was significantly and independently associated with better survival in multivariable analysis, whereas neither comorbidity index nor dose intensity of pre-transplant conditioning appeared to influence outcome. This study demonstrated feasibility of curative treatment with HCT for myelofibrosis aged 70 or older, with significant increases in HCT numbers and improved fitness of older adults over recent years.

Stem cell transplantation therapy for advanced liver damage -associated neurodegenerative disorders

Hepatic encephalopathy and other neurodegenerative disorders have profound implications for extensive liver impairment, calling for new ways of treating the condition. The application of stem cell transplantation to treat these severe disorders is a new and encouraging technique. This review article digs deep into the subject of stem cell transplantation therapy, neurodegenerative disorders associated with advanced liver damage, and liver transplantation. It comprehensively analyses the background, rationale, scope, and objectives of using stem cells to treat such challenging conditions. The topic of discussion includes the subtleties of neurodegenerative disorders, the function of liver transplantation, and the possible advantages and disadvantages associated with it. The relevance of patient selection, intraoperative concerns and post-transplant care is discussed. Further, the article explores how stem cell-based therapies can benefit from nanotechnology, specifically how it can improve stem cell distribution, survival, and integration for better therapeutic results. This review aims to offer a thorough analysis of regenerative medicine’s present and future possibilities in dealing with the intricate relationship between neurodegeneration and liver damage. It does this by examining the efficacy, safety, and long-term impacts of stem cell transplantation in treating neurodegenerative disorders associated with advanced liver damage. This will incorporate insights from ongoing clinical trials, the patent landscape, and future directions. The goal is to pave the way for innovative and personalized treatment approaches in this evolving research and clinical practice field. Therefore, these efforts represent a promising frontier in medical research that can alleviate the burden of HE and associated neurological complications combined with liver cirrhosis.

Retinitis pigmentosa and stem cell therapy.

Retinitis pigmentosa (RP) is a group of genetic disorders characterized by progressive degeneration of photoreceptors and retinal pigment epithelium (RPE) cells. Its main clinical manifestations include night blindness and progressive loss of peripheral vision, making it a prevalent debilitating eye disease that significantly impacts patients' quality of life. RP exhibits significant phenotypic and genetic heterogeneity. For instance, numerous abnormal genes are implicated in RP, resulting in varying clinical presentations, disease progression rates, and pathological characteristics among different patients. Consequently, gene therapy for RP poses challenges due to these complexities. However, stem cells have garnered considerable attention in the field of RPE therapy since both RPE cells and photoreceptors can be derived from stem cells. In recent years, a large number of animal experiments and clinical trials based on stem cell transplantation attempts, especially cord blood mesenchymal stem cell (MSC) transplantation and bone marrow-derived MSC transplantation, have confirmed that stem cell therapy can effectively and safely improve the outer retinal function of the RP-affected eye. However, stem cell therapy also has certain limitations, such as the fact that RP patients may involve multiple types of retinal cytopathia, which brings great challenges to stem cell transplantation therapy, and further research is needed to solve various problems faced by this approach in the clinic. Through comprehensive analysis of the etiology and histopathological changes associated with RP, this study substantiates the efficacy and safety of stem cell therapy based on rigorous animal experimentation and clinical trials, while also highlighting the existing limitations that warrant further investigation.

CRISPR-Cas9 Gene Editing Therapy, a Curative Hope for Sickle Cell in Nigeria, West Africa

Sickle cell anaemia is one of the haemoglobin abnormalities resulting from a genetic mutation— it is caused by inheriting two faulty genes that result in an abnormal substitution of glutamate for valine on the beta chain of haemoglobin, which causes haemoglobin molecules to stick together. According to a World Health Organization (WHO) report, 20 out of every 1,000 births suffer from sickle-cell anaemia, and 24% of Nigerians are carriers of this mutant gene. Scientists have suggested several solutions, including stem cell transplantation and gene therapies, but these have faced opposition due to ethical beliefs, high cost, and the ensuing immune issues. Research is now centered on advancing genome editing techniques for gene therapy. Ongoing studies have proven that genetic differences can be corrected methodically by modifying the genome at specific sites instead of introducing a new copy of the affected gene into the cells; due to the effectiveness of this method, scientists are testing its applications in manipulating genes in various systems. This review correlates a few studies that used the recently developed technique—CRISPR-Cas9—as a novel approach to gene therapy, dissecting the different clinical studies about sickle cell origin to point out many of its ethical and medical limitations, the consequences of these limitations, and the advancements this technology has made possible.

Enzymatic testing for mucopolysaccharidosis type I in Kuwaiti newborns: a preliminary study toward newborn screening.

Mucopolysaccharidosis type I (MPS I) is an autosomal recessive lysosomal storage disorder characterized by deficient or absent α-L-iduronidase (IDUA) enzyme activity due to pathogenic variants in the IDUA gene. Early treatment with hematopoietic stem cell transplantation and/or enzyme replacement therapy is associated with improved outcomes in this progressive multisystem disease. The diagnosis is usually delayed due to late presentation and non-specific symptoms, which result in high morbidity and mortality. The incidence of MPS I is unknown in Kuwait. This pilot study was undertaken to screen MPS I in all Kuwaiti neonates born at Farwaniya Hospital (FH), a major center in Kuwait, over 12 months. This study examined the incidence of MPS I for inclusion in the national newborn screening (NBS) to enable its early detection and adequate treatment. All Kuwaiti neonates born at FH between December 2021 and December 2022 were screened for MPS I. The screening consisted of determining IDUA enzyme activity in dried blood spot-derived samples using tandem mass spectrometry. A follow-up genetic analysis of the IDUA gene has been planned to screen the cases with diminished IDUA enzyme activity as second-tier testing. A total of 618 newborns, including 331 (54%) boys and 287 (46%) girls, were screened. Of them, 20 had deficient IDUA enzyme activity but showed negative genetic testing. However, we have diagnosed one additional female infant with MPS I who belonged to FH, but the parents chose to deliver in a private hospital. The molecular genetic study revealed the presence of a previously reported pathogenic nonsense variant in the IDUA c.1882C>T, which is associated with severe phenotype. That being included, MPS I is estimated to be approximately 0.2% of all screened cases in Kuwait. Our study is the first to evaluate the incidence of MPS I in Kuwait. Given the single center, small number of screened infants, and the short study duration thus far, it is premature to calculate the incidence. It is anticipated that as the study continues, we would be able to estimate the incidence in our population correctly. Screening newborns in all maternity hospitals in Kuwait is necessary to calculate the actual incidence of this severe disorder. Still, our preliminary data support the inclusion of MPS I in national NBS program to allow early initiation of treatment and thus improve disease outcome.

Loncastuximab Tesirine in the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma.

Currently, a significant percentage of patients with DLBCL are refractory or relapse after a first line of immunochemotherapy. Second relapses after autologous stem cell transplantation or chimeric antigen receptor T-cell therapies present few treatment options and do not yield good results. New molecules have entered the immunotherapy arsenal. Loncastuximab tesirine comprises a humanized anti-CD19 monoclonal conjugated antibody, which consists of an anti-CD19 antibody and cytotoxic alkylating agent, SG3199. Several studies have proven its efficacy in the treatment of refractory cases of DLBCL with a good safety profile, with the main adverse effects being neutropenia, thrombopenia, and liver enzyme involvement. In this review, we explain the mechanism of action of this molecule, the clinical data that have led to its acceptance by the FDA, and the new therapeutic options that are proposed in association with this drug.

The enigma of sickle cell hepatopathy: Pathophysiology, clinical manifestations and therapy.

Sickle cell disease (SCD) is one of the most common genetic disorders in the world predominantly affecting economically disadvantaged populations. There is a notable discrepancy between the growing adult SCD population and available diagnostic and therapeutic interventions for SCD. Sickle cell hepatopathy (SCH) is an all-inclusive term to describe the acute and chronic liver manifestations of SCD. The pathophysiology of SCH follows no defined pattern or sequence that poses challenges to clinicians and researchers alike. Evidence is lacking for this underreported disease at various levels from diagnostic to therapeutic options. This paper reviews the basic pathophysiology, clinical features, biochemical and radiological findings of various SCH manifestations and outlines the management of each condition. Old and new therapy options in SCD including hydroxyurea, red blood cell exchange transfusion, ursodeoxycholic acid, voxelotor, l-glutamine and crizanlizumab have been reviewed to investigate the role of these options in treating SCH. The role of liver transplant, haematopoietic stem cell transplant and gene therapy in SCH patients have been reviewed.

Exosome-mediated Repair of Intervertebral Disc Degeneration: The Potential Role of miRNAs.

Intervertebral disc degeneration (IVDD) is a serious condition that manifests as low back pain, intervertebral disc protrusion, and spinal canal stenosis. At present, the main treatment methods for IVDD are surgical interventions such as discectomy, total disc replacement, and spinal fusion. However, these interventions have shown limitations, such as recurrent lumbar disc herniation after discectomy, lesions in adjacent segments, and failure of fixation. To overcome these shortcomings, researchers have been exploring stem cell transplantation therapy, such as mesenchymal stem cell (MSC) transplantation, but the treatment results are still controversial. Therefore, researchers are in search of new methods that are more efficient and have better outcomes. The exosomes from stem cells contain a variety of bioactive molecules that mediate cell interactions, and these components have been investigated for their potential therapeutic role in the repair of various tissue injuries. Recent studies have shown that MSC-derived miRNAs in exosomes and vesicles have therapeutic effects on nucleus pulposus cells, annulus fibrosus, and cartilage endplate. miRNAs play a role in many cell activities, such as cell proliferation, apoptosis, and cytokine release, by acting on mRNA translation, and they may have immense therapeutic potential, especially when combined with stem cell therapy. This article reviews the current status of research on intervertebral disc repair, especially with regard to the latest research findings on the molecular biological mechanisms of miRNAs in MSC-derived exosomes in intervertebral disc repair.

Clinical presentation, diagnosis, and treatment of chronic granulomatous disease.

Chronic granulomatous disease (CGD) is caused by an impaired respiratory burst reaction in phagocytes. CGD is an X-linked (XL) (caused by pathogenic variants in CYBB) or autosomal recessive inborn error of immunity (caused by pathogenic variants in CYBA, NCF1, NCF2, or CYBC1). Female carriers of XL-CGD and unfavorable lyonization may present with the partial or full picture of CGD. Patients with CGD are at increased risk for invasive bacterial and fungal infections of potentially any organ, but especially the lymph nodes, liver, and lungs. Pathogens most frequently isolated are S. aureus and Aspergillus spp. Autoinflammation is difficult to control with immunosuppression, and patients frequently remain dependent on steroids. To diagnose CGD, reactive oxygen intermediates (O2 - or H2O2) generated by the NADPH oxidase in peripheral blood phagocytes are measured upon in vitro activation with either phorbol-12-myristate-13-acetate (PMA) and/or TLR4 ligands (E. coli or LPS). Conservative treatment requires strict hygienic conduct and adherence to antibiotic prophylaxis against bacteria and fungi, comprising cotrimoxazole and triazoles. The prognosis of patients treated conservatively is impaired: for the majority of patients, recurrent and/or persistent infections, autoinflammation, and failure to thrive remain lifelong challenges. In contrast, cellular therapies (allogeneic stem cell transplantation or gene therapy) can cure CGD. Optimal outcomes in cellular therapies are observed in individuals without ongoing infections or inflammation. Yet cellular therapies are the only curative option for patients with persistent fungal infections or autoinflammation.

Impact of COVID-19 monoclonal antibodies on outcomes of COVID-19 infection in hematopoietic stem cell transplant and chimeric antigen receptor therapy recipients.

Hematopoietic stem cell transplant (HSCT) and chimeric antigen receptor T-cell therapy (CAR-T) recipients are at higher risk of serious complications of COVID-19 infection than the general population. Though there is evidence that monoclonal antibodies (MCA) against COVID-19 reduce the risk of death and hospitalization in the general population, data regarding their efficacy in HSCT and CAR-T recipients remains scarce. We conducted a retrospective review of HSCT and CAR-T recipients to compare 30-day outcomes between patients who did and did not receive MCA after their first episode of COVID-19 between May 1, 2020 and December 31, 2022. Outcomes were defined as the most severe complication experienced out of the following: 30-day emergency department visit, hospitalization, intensive care unit admission, and death after COVID-19 infection. We identified 166 patients comprised of 53.6% allogeneic HSCT, 35.5% autologous HSCT, and 10.8% CAR-T recipients; 107 had received a COVID-19 vaccine >2 weeks prior to testing positive, and 40 were treated with MCA. After adjusting for age, presence of symptoms at the initial positive test, and COVID-19 vaccination status, patients who did not receive MCA were five times more likely to develop complications after COVID-19 infection (adjusted odds ratio 5.0 [95% CI, 1.9-12.8], p =.001). HSCT and CAR-T recipients who received MCA following COVID-19 infection were far less likely to develop COVID-related complications than those who did not receive MCA, regardless of vaccination status. This underscores the potential benefit of developing novel MCA with efficacy against circulating COVID-19 strains.

Patient engagement in hematopoietic stem cell transplantation and cell therapy: a survey by the EBMT patient engagement task force & transplantation complications working party.

The EBMT (European Blood and Marrow Transplantation Society) aims to connect patients, the scientific community, and other stakeholders to improve hematopoietic stem cell transplantation and cellular therapy outcomes. We performed a cross-sectional online survey to understand the perceptions regarding Patient Reported Outcomes (PROs) and Patient Active Involvement in Research (PAIR) in over 800 stakeholders (n = 813). Patients (n = 278) and health care professionals (HCPs) (n = 351) were compared. We observed high openness for EBMT PRO collection (n = 680, 84.5% across stakeholders' groups; patients n = 256, 93.1% versus HCPs n = 273, 78.4% [p < 0.001]) and PAIR (n = 702, 87.3% across stakeholder groups; patients n = 256, 92.4% versus HCPs n = 296, 85.8% [p = 0.009]), with a significantly higher proportion of patients expressing interest compared to HCPs. Priority domains for PROs data-collection identified were the assessment of symptom experience, psychosocial and cognitive functioning. The most important issues for patients specifically were the data-collection of PROs reflecting cognitive function, the option of reporting data at home, the importance of identifying actionable targets to improve their recovery, and receiving feedback on their input when participating in research projects. Our multistakeholder approach suggests an added value to embracing patient engagement in the development of meaningful research and service design within the transplantation and cellular therapy community.