Marrow Transplantation Research Articles

A-106 Determination of Urinary NGAL Reference Intervals from Specimens of Healthy Adult and Pediatric Individuals

Abstract Background Neutrophil gelatinase-associated lipocalin (NGAL) is a 25kDa protein implicated in multiple biological processes, including attenuation of apoptosis and differentiation of renal tubule epithelial cells and nephrons. NGAL is also produced and secreted by injured kidney tubule epithelial cells. As such, NGAL can serve as an early urinary biomarker for acute kidney injury (AKI). This multi-site, cross-sectional study aimed to establish reference intervals for urinary NGAL (uNGAL) in healthy pediatric and adult populations using a particle-enhanced turbidimetric assay. Methods Apparently healthy individuals, aged ≥ 3 months, were eligible for this study. Subjects with an active urinary tract infection (UTI) on the day of sample collection, acute kidney injury (AKI) or a history of AKI, stage 4 or 5 chronic kidney disease (CKD), known congenital anomalies of the kidney and urinary tract, known urothelial, urological, or kidney malignancies were excluded from the study. Subjects with uncorrected congenital heart disease, having undergone solid organ or bone marrow transplantation, receiving renal replacement therapy, and having undergone surgery (urologic, nephrectomy, or correction of congenital heart disease) were also excluded. A total of 688 subjects were screened, 677 were eligible, and 629 (91.4%) were considered evaluable per the protocol. The 59 excluded subjects were ineligible due to missing/incorrect information in the informed consent form, or not evaluable due to meeting exclusion criteria, mostly a positive UTI test. Urine samples were tested for NGAL on a Roche cobas® c501 analyzer in single determinations. Results Tables 1 and 2 describe the NGAL summary statistics and central 95% reference intervals by age and gender. Conclusions These data demonstrate the normal urine NGAL values in an apparently healthy pediatric and adult populations.

Exploring Novel Strategies to Alleviate Symptoms of β-Globinopathies: Examining the Potential Role of Embryonic ε-globin Induction

β-thalassemia and sickle cell disease are among the most prevalent genetic blood disorders globally. These conditions arise from mutations in the β-globin gene, leading to defective hemoglobin production and resulting in anemia. Current treatments include γ-globin inducers (e.g., Hydroxyurea), blood transfusions, iron chelation therapy, and bone marrow transplantation. Recently approved disease-modifying agents and promising gene therapies offer hope, yet their broad application is constrained by scalability challenges. Traditionally, research and development for β-globinopathies have focused on γ-globin induction. However, the ε-globin variant, which is active during early embryonic development and subsequently silenced prenatally, was once considered non-inducible by postnatal pharmacological means. Recent studies indicate that, akin to γ-globin, enhancing ε-globin expression could compensate for impaired β-globin synthesis, potentially ameliorating the clinical manifestations of β-globinopathies. This review critically examines the viability of ε-globin induction as a therapeutic strategy for β-thalassemia and sickle cell diseases. It also delves into the burgeoning research on the mechanisms governing ε-globin silencing and its pharmacological reactivation. We conclude with a discussion of prospective research directions and drug development initiatives aimed at exploiting ε-globin's therapeutic promise.

Pulmonary complications of bone marrow transplantation.

Bone marrow transplantation, now often known as haematopoietic stem cell transplantation (HSCT), is a complex choreographed procedure used to treat both acquired and inherited disorders of the bone marrow. It has proven invaluable as therapy for haematological and immunological disorders, and more recently in the treatment of metabolic and enzyme disorders. As the number of performed transplants grows annually, and with patients enjoying improved survival, a knowledge of both early and late complications of HSCT is essential for respiratory trainees and physicians in practice. This article highlights the spectrum of respiratory complications, both infectious and non-infectious, the timeline of their likely occurrence, and the approaches used for diagnosis and treatment, keeping in mind that more than one entity may occur simultaneously. As respiratory issues are often a leading cause of short- and long-term morbidity, consideration of a combined haematology/respiratory clinic may prove useful in this patient population.

Deubiquitination of RIPK2 by OTUB2 augments NOD2 signalling and protective effects in intestinal inflammation.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, but the molecular mechanisms underlying IBD are incompletely understood. In this study, we explored the role and regulating mechanism of otubain 2 (OTUB2), a deubiquitinating enzyme, in IBD. To study the function of OTUB2 in IBD, we generated Otub2-/- mice and treated them with dextran sulfate sodium (DSS) to induce experimental colitis. Bone marrow transplantation was performed to identify the cell populations that were affected by OTUB2 in colitis. The molecular mechanism of OTUB2 in signal transduction was studied by various biochemical methods. OTUB2 was highly expressed in colon-infiltrating macrophages in both humans with IBD and mice with DSS-induced experimental colitis. Colitis was significantly aggravated in Otub2-/- mice and bone marrow chimeric mice receiving Otub2-/- bone marrow. OTUB2-deficiency impaired the production of cytokines and chemokines in macrophages in response to the NOD2 agonist muramyl dipeptide (MDP). Upon MDP stimulation, OTUB2 promoted NOD2 signaling by stabilizing RIPK2. Mechanistically, OTUB2 inhibited the proteasomal degradation of RIPK2 by removing K48-linked polyubiquitination on RIPK2, which was mediated by the active C51 residue in OTUB2. In mice, OTUB2 ablation abolished the protective effects of MDP administration in colitis. This study identified OTUB2 as a novel regulator of intestinal inflammation.

Mineralocorticoid receptor expression and the effects of the mineralocorticoid receptor antagonist spironolactone in a murine model of graft-versus-host disease

PurposeThe topical administration of spironolactone, a mineralocorticoid receptor antagonist (MRA) improves dry eye symptoms in patients with ocular graft-versus-host disease (GVHD); however, the detailed mechanism remains unclear. This study aimed to investigate the effects of spironolactone eyedrops on the ocular surface using a chronic GVHD (cGVHD) mouse model and to determine the expression of the mineralocorticoid receptor (MR). MethodsA cGVHD mouse model was established by allogeneic bone marrow transplantation (BMT) from B10.D2 mice to BALB/c mice. Subsequently, cGVHD mice were treated with either 0.005 % spironolactone or vehicle eyedrops. The eyelids, cornea and conjunctiva of the recipients were analyzed at 4-week intervals post-BMT in both groups. ResultsSigns of ocular GVHD, such as corneal epithelial damage, depletion of meibomian glands, and inflammatory cell infiltration onto the ocular surface, were significantly decreased in cGVHD mice treated with spironolactone eyedrops. The expression of the MR NR3C2 in the corneal and conjunctival epithelia was significantly increased in cGVHD mice. HSP47+NR3C2+ MR-expressing fibroblasts, CD45+NR3C2+ MR-expressing leukocytes, and CD4+NR3C2+ MR-expressing T cells infiltrated the ocular surface tissue of cGVHD mice significantly more than that of syngeneic controls. ConclusionsMR expression is increased in epithelial cells, fibroblasts, and T cells in a murine cGVHD model, whereas MRA and spironolactone eyedrops could attenuate the severity of ocular GVHD. These findings suggest that MR signaling partially contributes to the development of ocular GVHD in this mouse model.

The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation: Organising committee

The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation: Organising committee

The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation: Van Bekkum Awards

The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation: Van Bekkum Awards

The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation: Psychiatry and Psychology Group - Poster Session (P756-P761).

The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation: Psychiatry and Psychology Group - Poster Session (P756-P761).

The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation: Pharmacist Committee – Poster Session (P762-P770)

The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation: Pharmacist Committee – Poster Session (P762-P770)

Refractory Thrombocytopenia is the Earliest Diagnostic Criterion for Sinusoidal Obstruction Syndrome in Children.

Sinusoidal obstruction syndrome (SOS) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT), whose diagnostic criteria changed over time to achieve a timelier diagnosis. Recently, pediatric-specific criteria presented by the European Society for Blood and Marrow Transplantation (pEBMT) incorporated transfusion-refractory thrombocytopenia (RT) as an early indicator of SOS in children. However, a comparison of all individual diagnostic parameters belonging to pEBMT and former SOS diagnostic criteria has never been performed. This retrospective study conducted at a pediatric tertiary care hospital analyzed all pediatric HSCT cases diagnosed with SOS among 170 children transplanted from 2009 to 2023. Eleven patients developed SOS during this period (incidence: 11/170, 6.5%). pEBMT, Seattle, and Baltimore criteria were retrospectively applied to the 11 cases and compared, showing that RT was the earliest fulfilled parameter (median onset: 6d post-HSCT). pEBMT and Seattle criteria identified 11/11 SOS cases, with pEBMT leading to an earlier diagnosis. RT typically manifested before diagnosis, with significantly higher platelet transfusion requirements before diagnosis than after. RT is the earliest satisfied criterion in pediatric SOS and typically occurs in the initial stages of the disease before diagnosis. Further research is needed to identify additional early indicators of pediatric SOS.

The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation: Quality Management Group - Poster Session (P783-P802).

The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation: Quality Management Group - Poster Session (P783-P802).

Allogeneic stem cell transplantation in de novo core-binding factor acute myeloid leukemia in first complete remission: data from the EBMT.

Core-binding factor acute myeloid leukemia (CBF-AML) represents 12-15% of all AML cases. Although CBF positivity infers a survival advantage, overall survival (OS) remains dismal. Treatment is with cytarabine/anthracycline-based chemotherapy induction followed by high-dose cytarabine (HiDAC) consolidation. Allogeneic hematopoietic stem cell transplantation (allo-SCT) is reserved for relapse or for patients having not achieved MRD-negativity at high risk for relapse. The role of SCT in first complete remission (CR1) remains controversial and is considered in high risk conditions. In this retrospective, multi-national, European Society for Blood and Marrow Transplantation (EBMT)-based study, we identified 1901 patients with de novo CBF-AML who received an allo-SCT or autologous transplantation (ASCT) in CR1. 65.5% harbored t(8;21) and 34.4% inv(16). In this group, the majority (77%) were treated with allo-SCT in CR1. In multivariate analysis, treatment with allo-SCT was an independent and significant, negative predictor of NRM and OS (HR 4.26, p < 0.0001 and HR 1.67, p = 0.003) and among patients treated with allo-SCT, those treated with MSD had the best outcomes, comparable to those treated with ASCT.There was no interaction between the type of transplant and MRD status at time of SCT. In both, MRD-negative and MRD-positive groups, NRM was worse in the allo-SCT group (MRD-: 12.9% vs 5.2%, p = 0.007; MRD+: 10.6% vs 0%, p = 0.004). We therefore demonstrated that consolidation in CR1 with allo-SCT results in worse outcomes than ASCT. Whether consolidation with ASCT yields better outcomes than chemotherapy alone or chemotherapy in combination with Gemtuzumab Ozogamicin is yet to be investigated.

The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians Award Winners (O001-O008).

The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians Award Winners (O001-O008).

The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation: Quality Management Group - Oral Session (O160-O163).

The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation: Quality Management Group - Oral Session (O160-O163).

The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation: Lectures.

The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation: Lectures.

The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation: Patient Advocacy - Oral Session (O164-O169).

The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation: Patient Advocacy - Oral Session (O164-O169).

The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation: Pharmacist Committee - Oral Session (O155-O159).

The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation: Pharmacist Committee - Oral Session (O155-O159).

The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians - Oral Session (O009-O154).

The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians - Oral Session (O009-O154).

The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation: Reviewers

The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation: Reviewers

The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation: Welcome Address

The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation: Welcome Address