Ophelia syndrome is a rare paraneoplastic limbic encephalitis associated with classical Hodgkin lymphoma (cHL), most often with antibodies against metabotropic glutamate receptor 5 (mGluR5). We describe a 19-year-old man with newly diagnosed cHL who presented with generalised seizures, cognitive dysfunction, spastic paraparesis, cauda equina-related autonomic dysfunction, and a 35 × 31 mm haemorrhagic inflammatory lesion in the right temporal lobe. Brain biopsy showed dense intravascular and perivascular inflammatory infiltrates without neoplastic cells. Cerebrospinal fluid demonstrated pleocytosis and intrathecal IgG synthesis with type III oligoclonal bands. Serum and cerebrospinal fluid neuronal autoantibody panels were negative, but mGluR5 antibodies were not assessed. Cervical lymph node biopsy confirmed nodular sclerosis cHL, stage IIA. After exclusion of infectious encephalitis and central nervous system lymphoma, the presentation was considered most consistent with Ophelia-like paraneoplastic limbic encephalitis. ABVD chemotherapy was initiated, with rapid neurological improvement after the first cycle. Complete metabolic response was achieved after two cycles and sustained after six cycles. At 15-month follow-up, major neurological symptoms had not recurred, although bladder and bowel dysfunction persisted. This case highlights the importance of considering paraneoplastic limbic encephalitis in cHL despite negative standard neuronal antibody testing and of documenting whether mGluR5 antibodies were assessed.
Background/Objectives: Revolutionary small molecule, targeted, tyrosine kinase inhibitors (TKIs) in the clinic have engendered the perception that optimal treatment has already been established for diseases like chronic myeloid leukemia (CML). Addressing BCR::ABL1 oncokinase domain mutations in CML is unlikely to redress disease recrudescence owing to persistent leukemia stem cells (LSCs). Therefore, it is necessary to consider an alternative strategic approach: disrupting LSC interactions with the protective microenvironment and/or immune system. The interaction of the TNF-α superfamily member, CD27, with its upregulated ligand, CD70, initiates survival signaling specifically in CML cells when BCR::ABL1 is inhibited by TKIs and thus represents an attractive target. Previous studies modulating the expression of CD27 on LSCs in a mouse model of advanced phase CML were encouraging. In our study, we explored the CD70/CD27 axis as a therapeutic target in early-phase disease. Methods: Primitive CD34+ cells from treatment-naïve chronic phase (CP) CML patients were drug-exposed in an in vitro co-culture system; combination drug treatments of the therapeutic anti-CD70 antibody and TKIs, nilotinib, were assessed in our CP CML murine model. Results: The blockade of the CD70/CD27 axis in combination with TKIs did not result in greater LSC elimination than with nilotinib as a single agent in our CP CML models. Nonetheless, there was an observed reduction in CD70+ cells with combination treatment. Conclusion: Further preclinical study of the antibody as an adjunct in CD70-expressing hematological malignancy is perhaps warranted.
Background/Objectives: Teclistamab is a B-cell maturation antigen (BCMA)-directed bispecific antibody approved for relapsed or refractory multiple myeloma (RRMM). Although prior analyses have summarized teclistamab outcomes, some have included combination regimens or broader comparative studies. Given the expanding real-world experience with teclistamab, we conducted a systematic review and meta-analysis focused on teclistamab monotherapy in RRMM. Methods: We performed a systematic review and meta-analysis of clinical trials and retrospective real-world studies evaluating teclistamab monotherapy in RRMM. The primary endpoint was overall response rate (ORR). Secondary endpoints included complete response (CR), overall mortality rate (OMR), mortality due to multiple myeloma progression, teclistamab-attributed mortality, adverse event-related mortality, grade ≥3 cytokine release syndrome (CRS), grade ≥3 immune effector cell-associated neurotoxicity syndrome (ICANS), and other grade ≥3 adverse events. Pooled proportions were estimated using random-effects models. Results: Twelve studies including 761 patients were analyzed, comprising two clinical trials and ten real-world retrospective cohorts. The pooled ORR was 60.9%, and the pooled CR rate was 25.2%. The pooled OMR was 26.9%, with mortality due to myeloma progression of 23.9%, adverse event-related mortality of 8.1%, and teclistamab-attributed mortality of 3.3%. Severe (grade ≥3) CRS and ICANS were uncommon, with grade ≥3 events occurring in 1.7% and 3.1%, respectively. Grade ≥3 infections occurred in 28.3%. Common grade ≥3 hematologic adverse events included lymphopenia, neutropenia, anemia, and thrombocytopenia. Conclusions: Teclistamab monotherapy demonstrates meaningful clinical activity and a manageable immune toxicity profile in heavily pretreated RRMM. However, severe infections and hematologic toxicities remain important clinical considerations, supporting the need for close monitoring, infection prevention, and supportive care during therapy.
Extramedullary Involvement (EMI) in Multiple Myeloma (MM) is a rare but aggressive entity that usually occurs in advanced or relapsed cases of MM. Although otologic manifestations aren’t frequent, they may mimic common inflammatory or neoplastic pathologies and could be a diagnostic challenge for the clinician. Case presentation: A 65-year-old woman with a history of Relapsed Refractory Multiple Myeloma (RRMM) presented at our outpatient Otolaryngology department with a four-month history of right-sided aural fullness and a minor episode of watery otorrhea. Otoscopy revealed an abnormal tympanic membrane lesion, and audiological evaluation showed moderate conductive hearing loss. The rest of the examination was normal. A Computed Tomography (CT) scan showed a soft-tissue mass occupying the tympanic membrane with associated temporal bone erosion. The history of RRMM and otoscopic and CT findings were indicative of EMI. After multidisciplinary consultation with a hematologist and radiologist, systemic therapy for relapsed disease was initiated, with consideration of adjunctive radiotherapy. However, the clinical course of the patient deteriorated and she eventually died due to her multiple comorbidities. Conclusions: EMI of the tympanic membrane is a rare entity, among the few reported cases with otologic involvement and it remains a diagnostic “challenge” because it resembles many other otologic conditions. Careful analysis of imaging findings in combination with the patient’s medical history is the key to accurate diagnosis. Early recognition is necessary to guide appropriate management, avoid unnecessary surgical intervention, and enable timely initiation of systemic therapy
Background: Pirtobrutinib has recently emerged as a promising first-line treatment option for chronic lymphocytic leukemia (CLL). Unlike currently established regimens, which are generally based on doublet combinations, pirtobrutinib can be administered as monotherapy. No head-to-head trials comparing pirtobrutinib with contemporary first-line combinations are currently available; hence, indirect comparative evidence may help define its potential role. Methods: A non-anchored indirect comparison based on reconstructed individual patient data (IPD) was conducted using published Kaplan–Meier curves from randomized controlled trials evaluating first-line treatments for CLL. Progression-free survival (PFS) was the endpoint of interest. Reconstructed IPD were generated using WebPlotDigitizer and the IPDfromKM algorithm. Then, Kaplan–Meier curves were plotted based on these patients, and the values of the restricted mean survival time (RMST) at 36 months were determined. Regarding PFS, pirtobrutinib monotherapy was compared indirectly with acalabrutinib plus obinutuzumab, venetoclax plus obinutuzumab, and venetoclax plus ibrutinib. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using univariate Cox models. The non-inferiority of pirtobrutinib monotherapy versus doublet regimens was assessed according to a non-inferiority margin set at HR = 1.15. Finally, the value-based prices of the new treatments were estimated based on a willingness-to-pay threshold of euro 30,000 per disease-free year gained and compared with the corresponding real prices in the Italian market. Results: The analysis included four randomized trials. Compared with pirtobrutinib monotherapy, HRs for PFS were 0.5544 (95%CI, 0.2696–1.1397) versus venetoclax plus obinutuzumab, 0.4583 (95%CI, 0.2066–1.0200) versus venetoclax plus ibrutinib, and 1.4453 (95%CI, 0.6684–3.1240) versus acalabrutinib plus obinutuzumab. Pirtobrutinib met the non-inferiority criterion compared with venetoclax plus obinutuzumab and venetoclax plus ibrutinib, but not with acalabrutinib plus obinutuzumab; however, these results were negatively affected by the small number of events in the pirtobrutinib arm, which generated wide CIs. In the preliminary pharmacoeconomic analysis, venetoclax plus obinutuzumab showed the most favorable profile in the comparison of value-based price vs. real price. Conclusions: This exploratory non-anchored analysis suggests that pirtobrutinib monotherapy may provide PFS outcomes broadly comparable to current first-line combination regimens for CLL. Given the methodological limitations inherent to indirect comparisons, prospective head-to-head studies are needed to clarify the optimal positioning of pirtobrutinib in treatment-naïve CLL.
BACKGROUND/OBJECTIVES:Lisocabtagene maraleucel (liso-cel) is a CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy approved for relapsed or refractory large B-cell lymphoma (R/R LBCL). However, most published meta-analyses of CAR-T therapy in LBCL pool data across products, limiting product-specific interpretation. METHODS:We conducted a systematic review and meta-analysis of clinical trials and retrospective real-world studies evaluating liso-cel monotherapy in R/R LBCL. The primary endpoint was the overall response rate (ORR). Secondary endpoints included complete response (CR), incidence of grade ≥ 3 adverse events, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), overall mortality rate (OMR), disease progression-related mortality, and adverse event-related mortality. Pooled proportions were estimated using random-effects models. RESULTS:Eleven studies including 1206 patients were analyzed, comprising five clinical trials and six real-world retrospective cohorts. The pooled ORR was 78%, and the pooled CR rate was 60%. The pooled OMR was 38%, with a disease progression-related mortality of 28% and an adverse event-related mortality of 4%. Severe (grade ≥ 3) CRS and ICANS occurred in 2% and 8%, respectively. Severe (grade ≥ 3) hematologic toxicities were frequent, particularly neutropenia, thrombocytopenia, and anemia. CONCLUSIONS:Liso-cel monotherapy demonstrated high pooled response rates and low pooled incidences of severe CRS and ICANS across clinical trials and real-world settings in R/R LBCL. Severe ICANS, although uncommon, remains clinically meaningful, and severe hematologic toxicities were frequent and warrant careful monitoring and supportive care. These findings provide product-specific benchmarks for liso-cel in R/R LBCL.
Background/Objectives: Thrombotic microangiopathies are rare, life-threatening hematological disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end-organ injury. This study was conducted in a setting where ADAMTS13 activity testing became available only from 2015 onward and complement-targeted therapy (eculizumab) had limited accessibility throughout most of the study period, conditions that shaped both diagnostic classification and treatment outcomes. Their clinical presentation, treatment response, and prognosis vary according to etiology, making early recognition and subtype classification clinically important. This study aimed to evaluate the etiological distribution, clinical features, treatment responses, and outcomes of adult patients with thrombotic microangiopathy at a tertiary-center real-world cohort. Methods: This retrospective cohort study included 47 adult patients (≥18 years) hospitalized with thrombocytopenia and microangiopathic hemolytic anemia (MAHA) in a nine-year period. Patients were classified as thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), or secondary TMA based on clinical and laboratory evaluation. Demographic characteristics, clinical manifestations, laboratory parameters, treatments, and outcomes were analyzed. Results: The mean age was 45.3 ± 15.2 years, and 72.3% of patients were female. Primary thrombotic microangiopathy accounted for 74.5% of cases, including thrombotic thrombocytopenic purpura in 53.2% and hemolytic uremic syndrome in 21.2%; secondary thrombotic microangiopathy accounted for 25.5%. Hemodialysis was required in all patients with hemolytic uremic syndrome compared with 16% of those with thrombotic thrombocytopenic purpura. The complete response rate was 74.5%, and in-hospital mortality was 25.5%. In multivariable Cox regression analysis, treatment non-response and reduced post-treatment estimated glomerular filtration rate independently predicted mortality. Conclusions: Adult TMAs are characterized by considerable etiological and clinical heterogeneity, which makes differential diagnosis challenging, particularly in settings where access to contemporary diagnostic tests and targeted treatments is limited. In this cohort, in the absence of ADAMTS13 testing, TTP was the most frequent subtype, while treatment non-response and renal impairment emerged as the main factors associated with mortality. These findings emphasize the need for early clinical recognition and careful subtype-based differential diagnosis, which will reduce morbidity and mortality by permitting rapid initiation of pathophysiology-based appropriate interventions, i.e., PEx, immune suppression and caplacizumab for immune TTP and anti-complement therapy for aHUS, and limiting the inappropriate use of PEx with its complications, including sepsis.
Background: This review aims to provide a comprehensive and practical overview of the evolving role of autologous transplantation in leukaemias, a strategy that was once largely abandoned but has recently regained interest in selected clinical settings. Methods: We reviewed the historical development of autologous transplantation in acute leukaemias, including the early period during which autologous transplantation was considered inferior to allogeneic approaches because of limited graft purification techniques and the inability to induce effective graft-versus-leukaemia (GVL)-like immune responses. We further summarise more recent experimental strategies aimed at improving stem cell purification and enhancing anti-leukaemic immune activity in autologous settings. In addition, we discuss how advances in measurable residual disease (MRD) assessment and molecular risk stratification have contributed to the renewed interest in autologous transplantation in selected subgroups of leukaemia patients. Results: This review identifies clinical situations in which autologous transplantation remains an important therapeutic option, including plasma cell leukaemia, where it continues to represent a standard first-line approach. We also discuss well-defined patient subgroups, particularly selected AML subtypes with intermediate-risk molecular profiles and acute promyelocytic leukaemia (APL) in second remission, in which outcomes following autologous transplantation may be comparable to, or occasionally superior to, those achieved with allogeneic transplantation. In contrast, autologous transplantation currently plays only a limited role in diseases such as chronic lymphocytic leukaemia (CLL) and chronic myeloid leukaemia (CML). Although attempts to induce potent anti-leukaemic immune effects in autologous settings have so far shown limited clinical efficacy, several emerging strategies appear promising and may further expand the role of autologous transplantation, particularly in elderly or frail patients. Discussion: Overall, current molecular and MRD-based risk stratification strategies, together with emerging immunological and graft-manipulation approaches, may redefine the role of autologous transplantation as a personalised therapeutic option in selected subgroups of leukaemia patients.
Anemia of chronic disease (ACD) is a condition linked to chronic immune activation secondary to a wide range of infectious, inflammatory, and autoimmune diseases. It is characterized by a state of iron-restricted erythropoiesis, in which prolonged activation of cytokines leads to retention of iron within the reticulo-endothelial system, driven primarily by hepcidin. Reduced iron availability contributes to a blunted response by erythropoietin and impaired erythropoiesis, in addition to a shortened red cell lifespan. In patients found to have anemia and evidence of chronic inflammation, parameters such as mean cell volume, iron studies, percentage of hypochromic red cells, reticulocyte hemoglobin content, and levels of ferritin, serum transferrin receptor, hepcidin, erythropoietin, and GDF15 are all used to build a picture of anemia of chronic disease. Following this, management normally utilizes erythropoietin-stimulating agents alongside parenteral iron supplementation when treatment of the underlying cause is not available. Newer therapies, such as hypoxia-inducible factor prolyl hydroxylase inhibitors and hepcidin inhibitors, also play a role, while cytokine targets, carbon dots, androgens, and other therapies are emerging as possible treatment routes. Despite its high prevalence, there remain few standardized methods of diagnosis or management in anemia of chronic disease. This narrative review explores long-standing and emerging practices in the diagnosis and management of this condition to ensure an up-to-date understanding.
Background: Patients with severe chronic anemia often require frequent blood transfusions. Many are elderly with comorbidities and limited mobility, making regular hospital visits burdensome. In some cases, patients may receive transfusions despite hemoglobin levels being above the clinical threshold due to logistical challenges, leading to unnecessary exposure to risks, inefficient use of blood units, and resource strain. This study aims to evaluate the use of point-of-care (POC) hemoglobin measurements under controlled outpatient clinic conditions, as an initial step toward potential future home-based monitoring by the patients or their caregivers, with the goal of optimizing transfusion timing, aiming to reduce unnecessary hospital visits while maintaining patient safety. Methods: A total of 127 patients from a hemato-oncology outpatient clinic at Carmel Medical Center were evaluated using a nurse-operated POC device to sample capillary blood, with 236 paired measurements concurrently analyzed via venous blood in the laboratory. Demographic and clinical data were assessed to evaluate factors associated with agreement between POC and laboratory measurements. Statistical analysis included Bland–Altman plots and Pearson correlation coefficients. Results: The POC device showed a moderate correlation with laboratory results (r = 0.73, p < 0.001), with a mean difference of 1.20 g/dL (SD = 1.94 g/dL) but wide limits of agreement (−3.20 to 5.50 g/dL). No significant differences were observed across demographic or clinical subgroups. Notably, all 156 paired measurements with POC-measured hemoglobin >7 g/dL were confirmed by laboratory testing. Conclusions: Although POC hemoglobin devices are not suitable as standalone tools for routine monitoring of chronic anemia, the high negative predictive value observed at the 7 g/dL threshold suggests that they may be useful for ruling out severe anemia. If validated in larger multicenter and home-use studies, POC Hb devices might contribute to reducing unnecessary hospital visits and transfusions.
Objective: To identify criteria which can be used locally to assess the quality of care for thalassaemia patients, leading to quality improvement measures. In low-resource settings, there is often minimal support for services, and the investigations used in patient monitoring are very basic. In order to select standards which can serve quality assessment, consideration is given to what is available in most centres. Importance is given to the need for the local service provider to self-assess the quality of care according to evidence-based minimal standards. Methods: A search in the recent literature was performed to identify measures of quality care in thalassaemia, selecting those which can be used in resource-poor settings. They are then compared to the standards listed in internationally accepted guidelines. Results: Twelve criteria were selected based on the routine information recorded by most centres. These include the following: clinical criteria: mean age (excluding paediatric clinics), pre-transfusion Hb < 9 g/dL, serum ferritin, MRI availability, heart iron (where available) >20 ms, LIC (where available) <3 mg/kg dw, LIC > 15 mg/kg dw, combination chelation within the last year, and BMI < 18.5 kg/m2. Social criteria (for adults): completed tertiary education, married/cohabiting, and employed full or part-time. Each is assigned a score with a total range from 0 to 10. Conclusions: Annual scoring according to achievements allows service providers to compare with previous years and conclude which of the basic services need to be further upgraded to achieve quality improvement. Scoring also allows for comparison with standards published in international guidelines. The clear aim is to aim for higher scores each year, indicating better patient outcomes.
Background and Clinical Significance: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome characterized by excessive activation of the immune system. Case Presentation: We present the case of an eight-month-old infant with influenza A(H1N1) who presented with seizures, hepatosplenomegaly, cytopenias, and markedly elevated levels of ferritin, IL-18, and CXCL9, raising concern for HLH. Despite initiation of HLH-directed and antiviral therapy, she succumbed to cardiorespiratory failure. Genetic testing revealed heterozygous variants in LYST and NLRC4, suggesting a potential genetic predisposition. Conclusions: This case underscores the challenge of distinguishing primary from secondary HLH and highlights the importance of balancing aggressive immunosuppression with infection control. Early genetic and cytokine profiling may assist in guiding personalized treatment strategies, enabling targeted interventions that avoid excessive immunosuppressive treatment in cases of reactive hyperinflammation while facilitating timely escalation of therapy in true or refractory HLH.
Surrogate endpoints are increasingly used in chronic lymphocytic leukemia (CLL) to accelerate treatment evaluation, but their validity is context-dependent. This review examines key endpoints—progression-free survival (PFS), time to next treatment (TTNT), measurable residual disease (MRD), and quality of life (QoL)/patient-reported outcomes (PROs). PFS, while standard, is limited by competing risks and poor reflection of toxicity and patient experience. TTNT captures both efficacy and tolerability but is influenced by external factors. MRD is a strong predictor of outcomes in fixed-duration venetoclax-based regimens but less reliable in continuous therapies. QoL and PROs provide essential patient-centered insight often missed by traditional endpoints. We propose a practical framework in which endpoint selection depends on treatment type, patient characteristics, and intended use. MRD is most informative after fixed-duration therapy, TTNT in continuous treatment, and PROs in vulnerable populations. Overall, surrogate endpoints in CLL require setting-specific validation to ensure they reflect meaningful clinical benefit.
Pernicious anemia (PA) represents a significant diagnostic challenge in neuropsychiatric patients due to its subtle and variable presentation. While PA is traditionally associated with clinical and biochemical manifestations of anemia, many patients, particularly those with neuropsychiatric symptoms, may have normal hematologic parameters, delaying recognition and appropriate treatment. Neurological and psychiatric symptoms, ranging from cognitive impairment and mood disorders to subacute combined degeneration (SCD) of the spinal cord, can precede hematologic abnormalities, leading to misdiagnosis or inappropriate management. The lack of a definitive gold standard test for cobalamin deficiency (CD) further complicates identification. Commonly used biomarkers, such as serum cobalamin, methylmalonic acid (MMA), homocysteine (Hcy), intrinsic factor antibodies (IFAs), and parietal cell antibodies (PCAs), each have limitations in diagnosing PA, especially in the absence of overt anemia. The variability in diagnostic criteria and cutoff values across studies adds to the challenge of achieving early and accurate diagnosis. This article reviews the complexities of diagnosing PA in neuropsychiatric patients, evaluates the limitations of current diagnostic methods, and emphasizes the need for a more comprehensive, standardized approach to early detection and treatment. Combining clinical awareness with improved biomarker interpretation is essential for preventing irreversible neurological damage and improving patient outcomes. Improved diagnostic protocols and further research are essential to optimize detection and minimize the risk of long-term neurological damage.
Below 32 °C, the second irreversible stage of platelet aggregation is absent, causing augmentation of the first reversible stage of platelet aggregation and adhesion. During rewarming, de-aggregation occurs; however, in the presence of adequate ADP (adenosine diphosphate), the second stage of aggregation occurs, leading to delayed rewarming thrombocytopenia (DRT). Erythrocytes leak ADP in sufficient amounts by 24 h to cause DRT. This is prevented by rewarming within 24 h. Heparin before hypothermia prevents platelet adhesion, as does alcohol, which also blocks the second phase of aggregation. Aspirin blocks the second phase of aggregation, and platelet infusions, stored without erythrocytes, are an effective therapy. DRT explains rewarming deaths in NCI (neonatal cold injury).
The COVID-19 pandemic exposed vulnerabilities in global blood supply systems and accelerated the adoption of patient blood management (PBM) strategies aimed at optimizing transfusion practices in surgical care. Perioperative anemia is a key contributor to adverse outcomes and is frequently treated with allogeneic blood transfusion (ABT), which carries infectious and immunologic risks. Iron deficiency remains the most common and potentially correctable cause of perioperative anemia. This narrative review examines various approaches to perioperative anemia, strategies to minimize reliance on ABT, and alternatives within the PBM paradigm. Evidence supports the use of iron therapy, erythropoiesis-stimulating agents, antifibrinolytic strategies, and blood conservation techniques to reduce transfusion requirements and improve clinical outcomes. Lessons from the COVID-19 pandemic highlight PBM as a framework to enhance transfusion safety and sustainability. Broader implementation of PBM may improve patient outcomes, reduce unnecessary transfusions, and preserve scarce blood resources.
Background: Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the management of relapsed or refractory hematologic malignancies, achieving high response rates in B-cell acute lymphoblastic leukemia, diffuse large B-cell lymphoma, and multiple myeloma. While the efficacy of CAR-T therapy is well established, quality of life (QoL) metrics have become increasingly important for guiding treatment decisions, patient counseling, and survivorship planning. Objectives: Most patients undergoing CAR-T therapy recover their initial QoL within 3 months, an improvement not typically seen with other treatment options. A comprehensive understanding of QoL is essential for delivering patient-centered care in the evolving CAR-T landscape. Conclusions: This review synthesizes current evidence on QoL outcomes in CAR-T recipients, including acute effects, recovery trajectories, comparisons with conventional therapies, and strategies to optimize QoL.
Background: Hemophilia care has undergone a major therapeutic transformation with the introduction of extended half-life products, non-replacement therapies, and gene therapy. However, the benefits of these advances are not equally distributed worldwide, and their impact on long-term musculoskeletal outcomes remains uncertain. Objective: To analyze global disparities in hemophilia care and research production in the context of recent therapeutic advances, with particular attention to musculoskeletal management, physiotherapy, and scalable strategies for resource-limited settings. Methods: A narrative review with a structured literature search was conducted. Two conceptual blocks were explored: global disparities and access to care in hemophilia, and recent therapeutic advances, including non-replacement therapies, extended half-life products, and gene therapy. Retrieved records were screened using Rayyan, and a structured workflow diagram was used to summarize the literature identification and selection process. A descriptive analysis was also performed to identify representative authors, institutions, and geographic patterns in hemophilia research. Results: The evidence shows substantial global disparities in diagnosis, access to treatment, healthcare infrastructure, and research production. Scientific output remains concentrated in high-income countries, while low- and middle-income regions are underrepresented. Advanced therapies consistently reduce bleeding rates and treatment burden, but concerns remain regarding access, affordability, durability, breakthrough bleeding, and long-term structural joint outcomes. Musculoskeletal complications, including subclinical bleeding and hemophilic arthropathy, remain clinically relevant despite improved hematologic control. Conclusions: The current paradigm shift in hemophilia care is not uniformly experienced worldwide. Addressing global disparities requires not only expanding access to advanced therapies, but also strengthening research capacity, implementing multidisciplinary care models, and integrating scalable interventions such as physiotherapy, patient education, and simplified diagnostic tools. Accessible musculoskeletal assessment strategies may help improve early detection, functional outcomes, and equity of care in resource-limited settings.
Background: Treatment options after Bruton's tyrosine kinase inhibitors (BTKi) failure in Waldenstrom macroglobulinaemia are limited. Methods: We retrospectively analysed the use of bortezomib after BTKi failure in 17 patients who were heavily pre-treated and chemotherapy-exposed at our centre between 2018 and 2025. Results: Reasons for BTKi failure were disease progression (59%) and intolerance (41%). At bortezomib initiation, the median age was 73 years and two patients experienced grade 1-2 neuropathy. The best overall response rate (ORR) was 88%. At a median follow up of 39 months (interquartile range 35-78), median treatment-free survival and overall survival were 18 (95% confidence interval [CI] 13-22) and 22 (95% CI 17-45) months, respectively. Conclusion: Bortezomib may be efficacious in patients who experience BTKi failure.
Objectives: For patients with multiple myeloma (MM), an increasing proportion of treatment is now delivered at home. While this shift offers convenience and supports continuity of care, it also demands new ways to ensure patient safety outside the hospital. Although patients receiving home-based treatment are generally clinically stable, each administration still requires a pre-treatment safety assessment, traditionally performed by telephone. We aimed to evaluate whether digital patient-reported outcomes (PROs) could replace these calls to determine treatment readiness. Methods: This feasibility study included 30 patients (median age 76 years, 60% male). Prior to each scheduled treatment, patients completed a digital symptom questionnaire. An algorithm stratified patients according to treatment readiness. In total, 233 questionnaires were distributed and 179 completed (completion rate 77%). Healthcare professionals were blinded to PRO data during the study, and PRO-based assessments were compared with standard nurse-led telephone evaluations after study completion. Results: Digital PRO data reliably identified patients ready for treatment. The algorithm achieved a positive predictive value of 100%, indicating concordance between PRO-based readiness classification and clinical decisions. The negative predictive value was 19%, reflecting that most patients reporting symptoms were ultimately eligible for treatment. Overall, nearly 80% of routine pre-treatment telephone calls could safely be omitted without compromising patient safety. Conclusions: This study suggests that digital PRO-based symptom reporting may support a reduction in routine pre-treatment telephone assessments for selected patients with MM receiving daratumumab. The approach showed potential for streamlining clinical workflows while maintaining patient safety, although confirmatory studies are needed before implementation.
