Background: Hydroxyurea-based cytoreduction before tyrosine kinase inhibitor (TKI) initiation remains common in newly diagnosed chronic-phase chronic myeloid leukemia (CML), yet its contemporary value is uncertain. Summary: This critical narrative review examines the historical rationale, biologic basis, clinical evidence, and guideline positions relevant to hydroxyurea use before or immediately around frontline TKI therapy. Hydroxyurea can lower leukocyte and platelet counts rapidly and may provide short-term symptomatic relief while diagnostic confirmation is pending or when definitive treatment access is briefly delayed. However, contemporary evidence does not support routine pretreatment in clinically stable chronic-phase CML. Observational studies have shown no improvement in European LeukemiaNet response milestones, no acceleration of molecular response kinetics, and possible disadvantages including delayed TKI initiation, greater hematologic toxicity, and more treatment interruptions. Randomized studies evaluating early hydroxyurea together with imatinib likewise have not demonstrated meaningful molecular or hematologic benefit over TKI therapy alone. Current guidelines consistently position hydroxyurea as a selective, time-limited bridging option rather than a standard pretreatment strategy. Key Messages: In modern practice, the priority should be rapid initiation of definitive BCR::ABL1-directed therapy once the diagnosis is confirmed and access is secured. Hydroxyurea retains a limited role in selected situations such as symptomatic proliferative burden, suspected leukostasis, clinically important thrombocytosis, or short unavoidable logistical delay to TKI initiation.

Background: Classical Philadelphia-negative myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, and myelofibrosis, frequently occur in patients with renal, hepatic, cardiovascular, or hematologic comorbidities. These vulnerabilities complicate treatment selection, dose adjustment, and toxicity monitoring. However, patients with advanced kidney disease, dialysis dependence, decompensated cirrhosis, severe cytopenias, or overlapping organ impairment are often underrepresented in prospective trials. Summary: This narrative review presents a practical, organ-adapted framework for selecting MPN therapy in clinically complex patients. We define renal and hepatic impairment, compare commonly used cytoreductive and targeted therapies, including hydroxyurea, busulfan, anagrelide, ruxolitinib, fedratinib, momelotinib, pacritinib, ropeginterferon alfa-2b, and pegylated interferon alfa-2a, and discuss their use in dialysis, decompensated liver disease, cytopenic myelofibrosis, anemia-dominant myelofibrosis, and combined organ vulnerability. The proposed approach prioritizes label-based dose modification when available, cautious dose initiation when evidence is extrapolated, structured early monitoring, and multidisciplinary review for high-risk patients. Key Messages: Management of Philadelphia-negative MPNs in organ dysfunction should be individualized according to disease phenotype, treatment goal, organ reserve, hematologic tolerance, frailty, and label-specific safety restrictions. In renal impairment, hydroxyurea and ruxolitinib may remain feasible in selected patients when dose-adjusted and monitored closely, whereas dialysis and severe renal impairment require conservative initiation and multidisciplinary review because direct evidence remains limited. In myelofibrosis, JAK inhibitor choice should be phenotype-adapted; ruxolitinib remains a common standard when blood counts and organ function permit, momelotinib is attractive in anemia-dominant disease, pacritinib is particularly relevant in severe thrombocytopenia, and fedratinib is useful in selected settings but requires thiamine-focused safety management. In hepatic dysfunction or overlapping organ vulnerability, therapy should prioritize safety, reversible contributors, conservative starting strategies, explicit stopping rules, and early reassessment.

Sickle cell disease (SCD) is characterized by recurrent vaso-occlusion, hemolysis, and chronic inflammation, leading to acute painful crises and progressive organ damage. Despite standard supportive and disease-modifying therapies, many complications remain difficult to manage. Hyperbaric oxygen therapy (HBOT) increases dissolved oxygen delivery to hypoxic tissues and may reduce sickling and ischemia-reperfusion injury. This narrative review summarizes the mechanistic rationale and available clinical evidence for HBOT in SCD-related complications, including bone disease, chronic leg ulcers, ophthalmic ischemia, and priapism. Current evidence is limited to case reports, small series, and early-phase studies with heterogeneous protocols. Reported benefits include improved pain control and tissue healing in selected patients. HBOT appears generally well tolerated, but its role remains undefined. Prospective, controlled trials are needed to establish efficacy and optimal use.

BackgroundEmapalumab, an interferon-γ (interferon-gamma)–blocking monoclonal antibody, has emerged as a targeted therapy for refractory hemophagocytic lymphohistiocytosis (HLH). This scoping review summarizes real-world evidence of its clinical use across HLH subtypes.MethodsA comprehensive search of PubMed, Scopus, and Web of Science through September 2025 identified studies reporting emapalumab use outside clinical trials. Case reports, series, and observational studies describing clinical outcomes were included.ResultsThirty-one publications comprising 86 patients were analyzed. Disease contexts included familial/genetic HLH (n = 11), rheumatology-associated macrophage activation syndrome (MAS; n = 12), malignancy-associated HLH (n = 25), infection-associated HLH (n = 22), CAR-T/IEC-HS or cytokine-release-syndrome–related HLH (chimeric antigen receptor T-cell/immune effector cell–associated hemophagocytic syndrome; n = 11), and other secondary HLH (n = 5). Across all categories, emapalumab achieved rapid suppression of hyperinflammation, typically within 1–2 weeks. Clinical response rates were 100% in familial HLH, 91.7% in rheumatology-associated MAS, 72.7% in infection-associated HLH, 90.9% in CAR-T/IEC-HS–related HLH, and 80% in other secondary HLH. In contrast, only 6 of 25 patients with malignancy-associated HLH (24%) showed partial or complete responses, reflecting inferior outcomes due to underlying disease progression. Overall survival was highest in familial and infection-associated subgroups. The reported adverse events were generally infrequent and mild in the published cases, but causality cannot be reliably established given the complexity of the underlying disease and concurrent therapies.ConclusionReal-world evidence demonstrates that emapalumab induces rapid and durable disease control across diverse HLH subtypes, with a favorable tolerability profile. However, outcomes remain markedly inferior in malignancy-associated HLH, where response rates are limited to approximately 24%, primarily due to the impact of underlying malignancy. Its role as rescue or bridging therapy to hematopoietic stem-cell transplantation (HSCT) is increasingly supported in both pediatric and adult populations.

Background Myeloid neoplasms harboring both an isolated deletion of chromosome 5q (del(5q)) and myeloproliferative neoplasm (MPN) driver mutations ( JAK2, CALR, MPL ) constitute a rare and diagnostically challenging subset, often described with features overlapping those of myelodysplastic syndromes (MDS) and MPN. Methods We systematically reviewed published case reports and case series of adult patients with myeloid neoplasms and concomitant isolated del(5q) and MPN driver mutations. A comprehensive search of PubMed and Google Scholar from inception through 31 December 2024 was performed using terms related to “del(5q)”, “ JAK2”, “CALR”, “MPL” , and “myeloid neoplasm”. Eligible reports required documentation of isolated del(5q) and at least one MPN driver mutation with extractable clinical, cytogenetic, and/or molecular data. Data were synthesised descriptively; no quantitative meta-analysis was feasible. The review followed PRISMA 2020 guidelines and was registered post-study at INPLASY2025120046. Results Twenty publications reporting 24 patients (diagnosed between 2006 and 2021) met the inclusion criteria. The median age was 70.5 years with a female predominance. Most patients presented with macrocytic anemia, thrombocytosis, and megakaryocytic dysplasia, frequently accompanied by marrow fibrosis. JAK2 V617F was the predominant mutation, whereas CALR and MPL were rarely described. Lenalidomide achieved hematologic responses in 14 of 17 evaluable patients and cytogenetic responses in 8 of 16; JAK2 V617F clearance occurred in 4 of 13. During a median follow-up of approximately two years, 5 of 24 patients progressed to acute myeloid leukemia. Conclusion Reported cases with isolated del(5q) and an MPN driver mutation suggest a rare overlap presentation with mixed dysplastic and proliferative features. Lenalidomide appears to provide hematologic and cytogenetic benefit in some patients, although molecular persistence and progression to AML have been observed. Given the limited number and heterogeneity of published cases, these observations should be interpreted with caution. Larger, systematically collected datasets are needed to better understand the clinical significance and optimal management of this combination.

BACKGROUND:Therapeutic advances in chronic lymphocytic leukaemia (CLL) have made treatment selection far more nuanced than in the chemoimmunotherapy era. Patients now have access to two principal therapeutic strategies: continuous therapy with Bruton's tyrosine kinase inhibitors (BTKis) or fixed-duration regimens combining venetoclax with CD20 monoclonal antibodies and/or BTKis. These strategies carry fundamentally different safety profiles, monitoring requirements, and logistical demands, necessitating a treatment-specific approach to fitness assessment. SUMMARY:The objective of this article was to synthesise current evidence and propose a practical, treatment-specific fitness assessment framework for patients with CLL, enabling physicians to match patient characteristics to the most appropriate targeted therapy. This was a narrative review of the literature from PubMed, Scopus, and Embase. Landmark randomised controlled trials, contemporary expert opinion papers, and current guidelines from ESMO, ASCO, and ESC were reviewed. The two therapeutic paradigms impose distinct fitness demands. For continuous BTKi therapy, cardiovascular comorbidity is the dominant determinant, given the class-effect risk of atrial fibrillation and hypertension. For fixed-duration venetoclax-based regimens, the key determinants instead shift to renal function and tumour burden, which govern tumour lysis syndrome risk, and to the social support and hospital access required for intensive ramp-up monitoring. Building on this distinction, the landmark phase 3 CLL17 trial (N Engl J Med, 2026) demonstrated that fixed-duration venetoclax-obinutuzumab and venetoclax-ibrutinib are non-inferior to continuous ibrutinib, with superior rates of undetectable minimal residual disease and lower treatment discontinuation, particularly in older patients. Notably, frailty - better conceptualised as lower resilience - is dynamic rather than fixed and may improve during effective targeted therapy. Structured pre-treatment screening can be performed with validated instruments such as the G8, VES-13, GAH, and the Canadian Study of Health and Aging Clinical Frailty Scale (CSHA-CFS); however, no single tool has yet been prospectively validated for outcome prediction specifically with BTKi or BCL-2 inhibitor therapy, and addressing this evidence gap is a priority for future research. KEY MESSAGES:A treatment-specific, individualised fitness assessment - rather than an age-based or aggregate comorbidity score - is the appropriate framework for CLL in the targeted therapy era. Most patients, including those with lower resilience, are candidates for targeted therapy; the clinical imperative is to match each patient to the treatment best suited to their specific fitness profile.

Introduction: Tyrosine kinase inhibitors (TKIs) are the cornerstone of therapy for chronic myeloid leukemia (CML). Although nephrotoxicity has been reported, existing evidence remains inconsistent, with limited data from the Gulf region. This study aimed to evaluate the impact of TKIs on renal function among patients with CML treated at Hamad Medical Corporation (HMC), Qatar. Methods: This retrospective, single-center study included adults with CML who received a TKI between 2016 and 2023. The primary outcome was the change in estimated glomerular filtration rate (eGFR) over time. Secondary outcomes included acute kidney injury (AKI), chronic kidney disease (CKD) and the need for dialysis. Repeated-measures analysis of variance was used to assess unadjusted eGFR trends. Linear mixed-effects modeling was used to assess longitudinal eGFR trends while adjusting for baseline comorbidities. Results: A total of 209 patients were followed for a median of 69.3 months (IQR, 39.4-117.8). Imatinib was the most frequently prescribed TKI (n = 136, 65.1%), followed by dasatinib (n = 39, 18.7%) and nilotinib (n = 34, 16.3%). The mean baseline eGFR was 93.8 mL/min/1.73 m2 (SD 26.3) and showed no significant decline at 3 months (p = 0.498), 3 years (p = 0.112), or 8 years (p = 0.297). However, among dasatinib-treated patients, eGFR significantly decreased from 87.5 (SD 16.7) to 76.8 (SD 11.4) over 3 years (p = 0.042). Multivariate mixed-effects modeling revealed that this reduction was confounded by hypertension (p < 0.001). After adjusting for comorbidities, no significant difference in eGFR decline was observed between the TKI groups. AKI occurred in 17 (8.1%) patients, CKD in 4 (1.9%), and none required dialysis. No significant differences were observed across TKI types. Conclusion: Renal function remained largely stable during long-term TKI therapy. Initial declines to dasatinib were largely comorbidity-driven, pointing to the need for cardiovascular risk assessment in this population.

INTRODUCTION:Tyrosine kinase inhibitors (TKIs) have transformed chronic-phase chronic myeloid leukemia (CML) into a chronic condition with excellent long-term survival. As outcomes improve, attention has shifted toward treatment-related metabolic effects and survivorship issues. Body weight and body mass index (BMI) are important indicators of metabolic health; however, the long-term effects of TKIs on these parameters remain incompletely characterized, particularly in real-world settings. This study evaluated longitudinal changes in body weight and BMI in adults with chronic-phase CML treated with TKIs. METHODS:We conducted a retrospective longitudinal observational study at a tertiary care center between January 2016 and December 2023. Adult patients with chronic-phase CML who initiated TKI therapy and had baseline and follow-up weight measurements were included. Patients with major preexisting metabolic conditions or factors likely to confound weight were excluded. Body weight and BMI were assessed at predefined time points up to 7 years. Paired analyses evaluated within-patient changes over time, and stratified analyses were performed according to initial TKI and cumulative exposure patterns. RESULTS:A total of 175 patients were included in the analytic cohort (82.9% male; mean age 39.2 ± 11.7 years). The marked male predominance and younger age reflect the demographic context of CML care in Qatar. Mean baseline weight was 68.2 ± 14.4 kg, and baseline BMI was 24.6 ± 3.9 kg/m2. Weight increased significantly from baseline at 6 months (+4.27 kg), 12 months (+6.00 kg), 18 months (+6.63 kg), and 24 months (+6.41 kg) (all p < 0.001). At the last follow-up, the mean weight gain was 6.12 kg (p < 0.001), with 56.9% of patients achieving ≥5% weight gain. The temporal pattern showed rapid weight gain during the first 6-12 months, followed by stabilization through 2-3 years with persistent elevation thereafter. Weight and BMI increases were observed across all first-line TKIs and cumulative exposure groups, without statistically significant differences between agents. CONCLUSION:In this real-world cohort of adults with chronic-phase CML, TKI therapy was associated with early and sustained increases in body weight and BMI, largely occurring within the first year of treatment. These changes likely reflect a combination of treatment-related metabolic effects and reversal of cancer-associated catabolism. Given the long life expectancy of patients with CML, routine metabolic surveillance, early lifestyle interventions, and prospective studies incorporating metabolic biomarkers, body composition, edema assessment, treatment response, and toxicity outcomes should be incorporated into long-term CML survivorship research and care.

Myelofibrosis (MF) is a Philadelphia chromosome–negative myeloproliferative neoplasm characterized by progressive bone marrow fibrosis, constitutional symptoms, cytopenias, and splenomegaly. Splenic enlargement, driven primarily by extramedullary hematopoiesis, represents a hallmark of MF and contributes substantially to symptom burden, portal hypertension, and worsening cytopenias through splenic sequestration. The identification of constitutive Janus kinase–signal transducer and activator of transcription (JAK–STAT) pathway activation as the central pathogenic mechanism in myeloproliferative neoplasms led to the development of JAK inhibitors, which have become the cornerstone of therapy for spleen volume reduction and symptom amelioration. Four JAK inhibitors—ruxolitinib, fedratinib, pacritinib, and momelotinib—are currently approved by regulatory agencies, each exhibiting distinct pharmacological profiles suited to different clinical phenotypes. Ruxolitinib remains the first-line standard for patients with adequate platelet counts, pacritinib is preferred in severe thrombocytopenia, and momelotinib is the agent of choice in anemia-dominant disease. Fedratinib serves as an effective second-line option following ruxolitinib failure. Emerging combination strategies, including pelabresib plus ruxolitinib and navitoclax plus ruxolitinib, have demonstrated superior spleen volume reduction in phase III trials and represent a promising therapeutic frontier. Conventional agents such as hydroxyurea and immunomodulatory drugs retain a role in select patients. Non-pharmacologic interventions—including splenectomy, splenic irradiation, partial splenic artery embolization, and radiofrequency ablation—remain valuable for patients refractory to or ineligible for medical therapy. This review provides a comprehensive and updated overview of the management of splenomegaly in MF, integrating all four approved JAK inhibitors, emerging combination therapies, peri-transplant considerations, and procedural approaches, and proposes a practical phenotype-driven treatment framework.

BACKGROUND:Acute myeloid leukemia (AML) is a biologically heterogeneous and clinically aggressive hematologic malignancy, with outcomes that remain poor for many older adults and patients with adverse-risk disease. Advances in cytogenetics and next-generation sequencing have identified actionable molecular lesions, including FLT3, IDH1/2, and NPM1, enabling biomarker-driven risk stratification and more individualized therapeutic approaches. SUMMARY:Since 2017, multiple targeted therapies and antibody-drug conjugates, often combined with intensive chemotherapy or hypomethylating agents, have improved remission rates in molecularly defined AML subsets. Measurable residual disease (MRD) assessment using multiparameter flow cytometry and molecular assays is increasingly incorporated into post-remission evaluation to inform decisions regarding transplantation and maintenance therapy. However, its clinical utility remains limited by assay variability, interference from clonal hematopoiesis, and the lack of robust evidence supporting MRD-directed interventions. This narrative review synthesizes the evolving genomic landscape of AML, current guideline-endorsed targeted therapies, and emerging investigational strategies, while outlining a practical framework that integrates genomic profiling, MRD-informed decision-making, and algorithmic treatment pathways. KEY MESSAGES:Precision medicine is reshaping AML management through genomic classification, targeted therapies, and evolving MRD applications. A practical treatment framework that incorporates molecular profiling and post-remission risk assessment may improve clinical decision-making, although real-world barriers to implementation and issues of equity remain important challenges.

Abstract. Background: During the last few decades, screening for dysglycemia in transfusion-dependent β-thalassemia patients (β-TDT) with an oral glucose tolerance test (OGTT) using fasting (FPG) and 2-hour plasma glucose (2h-PG) samples has been recommended at 10, 12, 14, and 16 years and annually thereafter. A precise measurement of blood glucose (BG) concentration is the mainstay for an accurate diagnosis of dysglycemia, in order to limit the risk of false-positive (i.e., overdiagnosis) and false-negative (i.e., underdiagnosis) results, especially in patients with BG values near the cut-off values. Research objective: The primary objective of our survey was to describe the procedures followed during the pre-analytical phase of screening for dysglycemia, based on the actual clinical practice of Centers following β-TDT patients. Answers from the survey were compared with international recommendations (American Diabetes Association and World Health Organization). Methods: This observational study was based on an online questionnaire survey. All members of the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) were officially invited. The questionnaire consisted of 6 sections and 22 questions, including single-choice, multiple-choice, and open-ended descriptive answers. Results: 14 out of 18 invited Centers [Bulgaria, Cyprus, Greece, Iran (2), Italy (2), Oman, Qatar, Sri Lanka, Türkiye (3) and United Kingdom] accepted and completed the survey promoted by the ICET-A with a response rate of 77.7 % The total number of β-TDT patients followed in the participating Centers was 3,372 and 2,932 (86.9 %) were over the age of 10 years. The total number of thalassemia related diabetes mellitus (Th-RDM) reported by all Centers was 549. The total mean prevalence of Th-RDM was 14.7 ± 10.2 % . Generally, the survey has shown that there was a variable adherence to, and deviations from, current international guidelines. The lowest adherence rate regarded the information and instructions given to patients prior to OGTT (~56%), and how the BG samples were stored from the time of collection to time of centrifugation and analysis (~80 %). Differences in these factors may result in unintended variations in the prevalence of dysglycemia and have important implications for clinical practice. Conclusions: Many factors across the total testing process (sample collection, storage and transport during the preanalytical phase) can significantly impact OGTT accuracy and reproducibility, especially in patients with blood glucose values closer to the cut-off values. To minimize pre-analytical errors, a more precise diagnostic approach associated with closer patient follow-up is needed to reduce the risk of errors in glucose measurement.

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy driven by severe ADAMTS13 deficiency with consequent ultra-large von Willebrand factor-mediated microthrombosis. Over the last two decades, understanding of the ADAMTS13–vWF axis has transformed management and made TTP a model for precision medicine. This narrative review (adult focus) synthesizes contemporary evidence on diagnosis, treatment, genetics, and emerging therapies in immune-mediated TTP. We summarize a pragmatic, biomarker-guided algorithm integrating early therapeutic plasma exchange and corticosteroids, upfront rituximab to suppress anti-ADAMTS13 autoimmunity, and caplacizumab to block vWF–platelet interactions; define escalation strategies for refractory disease (e.g., proteasome inhibition); and formalize treat-to-target de-escalation anchored to ADAMTS13 recovery. We emphasize the role of rapid ADAMTS13 assays for front-door triage, routine ADAMTS13 monitoring in remission, and preemptive rituximab at biochemical relapse to avert clinical recurrence. Precision diagnostics are extended by genetic markers (e.g., HLA associations) and emerging biomarkers that may refine relapse risk. Finally, we discuss near-term opportunities—point-of-care ADAMTS13 assays, longer-acting vWF-pathway inhibitors, and data-driven risk tools—that can further individualize timing and intensity of therapy. Collectively, a biomarker-first strategy offers a clear path to fewer exacerbations, fewer relapses, and more consistent outcomes.

Introduction Transformed follicular lymphoma (t-FL) is an aggressive lymphoma with limited prospective evidence to guide treatment, particularly in the relapsed setting. We summarized the current evidence on emerging cellular and targeted therapies that extend beyond conventional chemoimmunotherapy. Methods This scoping review was conducted in accordance with the PRISMA extension for Scoping Reviews (PRISMA-ScR) and structured using the Population–Concept–Context (PCC) framework. Adults with histologically confirmed or strongly suspected t-FL were the population of interest. Findings were synthesized narratively. Results Seventeen studies met inclusion criteria across three therapeutic categories: CAR-T therapy (7 interventional trials, n = 130 t-FL patients in reported subsets), CD20×CD3 bispecific antibodies (BsAbs; n = 61 t-FL patients with extractable outcomes), and selinexor (n = 31 t-FL patients); together encompassing approximately 222 t-FL patients across primary interventional cohorts with extractable outcomes. CAR-T products achieved overall response rates (ORR) of 52–83% and complete response (CR) rates of 40–58%; randomized second-line trials favored axicabtagene ciloleucel and lisocabtagene maraleucel over standard care. In real-world CAR-T series, ORR ranged from 82–92% and CR rates from 64–67% across registry cohorts. BsAbs were active in heavily pretreated disease (epcoritamab ORR 50%/CR 44%; glofitamab ORR 55%/CR 35%), with predominantly low-grade cytokine release syndrome. Selinexor showed more modest efficacy (ORR 39%/CR 16%) but durable benefit in complete responders. Conclusions Current evidence supports a stepwise treatment framework: DLBCL-like induction at transformation, autologous stem-cell transplant in fit, chemosensitive responders, CAR-T as the preferred option at first relapse, BsAbs after CAR-T or when cellular therapy is not feasible, and selinexor in later-lines of therapy. Additional prospective t-FL–inclusive trials are needed to refine treatment selection and biomarker-guided sequencing.

Background:Over the last few decades, screening for dysglycemia in transfusion-dependent β-thalassemia patients (β-TDT) using an oral glucose tolerance test (OGTT) with fasting (FPG) and 2-hour plasma glucose (2h-PG) samples was recommended at 10, 12, 14, and 16 years, and annually thereafter. The precise measurement of PG levels is the mainstay for accurate diagnosis of dysglycemia and for limiting the risk of false-positive (i.e., overdiagnosis) and false-negative (i.e., underdiagnosis), especially in patients with PG values near the recommended cutoff values. Research objective:The primary objective of the survey was to describe the procedures of the preanalytical phase of screening for dysglycemia, using data from actual clinical practice at Centers caring for β-TDT patients. The collected data were compared to the international recommendations of the American Diabetes Association and the World Health Organization. Methods:This observational study was based primarily on an online questionnaire. All members of the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) were officially invited to participate. The questionnaire consisted of 6 sections and 22 questions, with single-, multiple-choice, and open-ended descriptive answer options. Results:14 out of 18 invited Centers [Bulgaria, Cyprus, Greece, Iran (2), Italy (2), Oman, Qatar, Sri Lanka, Türkiye (3) and United Kingdom] accepted and completed the survey with a response rate of77.7 % The total number of β-TDT patients followed in the participating Centers was 3,372 with 2,932 (86.9 %)over the age of 10 years. A total of 549 patients were followed for thalassemia-related diabetes mellitus (Th-RDM). Furthermore, the survey across the 10 countries showed variable adherence to and deviations from current international guidelines. The lowest adherence rate was associated with the information and instructions given to patients prior to the OGTT and with how the blood samples were stored from collection to centrifugation and analysis. Differences in these factors may lead to unintended variations in the prevalence and severity of hyperglycemia, with important implications for clinical practice. To improve the quality of the pre-analytical phase across participating centers, the Standards for Reporting of Diagnostic Accuracy (STARD) statement was implemented. Conclusions:Based on the STARD statement, the pre-analytical blood sampling procedures for OGTT screening in thalassemia Centers require revision and standardization. To minimize preanalytical errors, a precise diagnostic approach, coupled with closer patient follow-up, is needed to reduce the risk of glucose measurement errors.

Anemia of chronic disease (ACD), also referred to as anemia of inflammation, is a prevalent and clinically significant complication of chronic infection, autoimmune disease, malignancy, and chronic kidney disease. It is characterized by inflammation-driven iron sequestration, impaired erythropoietin (EPO) production and signaling, and suppression of effective erythropoiesis. Current therapies (iron supplementation and erythropoiesis-stimulating agents) often address downstream consequences and may be limited by hepcidin-driven functional iron deficiency, cytokine-mediated EPO resistance, and safety concerns in vulnerable populations. This review re-examines ACD through an integrated framework of hepcidin dysregulation, iron sequestration, and inflammatory inhibition of the EPO axis. We then synthesize emerging evidence that sodium-glucose cotransporter 2 (SGLT2) inhibitors produce sustained increases in hemoglobin/hematocrit beyond transient hemoconcentration across cardiovascular and kidney disease trials, including in non-diabetic populations. Mechanistic studies suggest a coordinated biologic response that may include reduced hepcidin, improved iron mobilization, physiologic augmentation of endogenous EPO, and attenuation of systemic inflammation-pathways directly relevant to ACD. We critically re-appraise current ACD paradigms by contrasting downstream "replacement" strategies (iron and ESAs) with pathway-level approaches (HIF-PHIs and SGLT2 inhibition), and we outline biomarker-guided study designs to test whether SGLT2 inhibition may act as an adjunctive physiologic modulator of iron-erythropoietic crosstalk in well-phenotyped inflammatory anemia cohorts, while emphasizing that current evidence remains hypothesis-generating rather than practice-changing.

Precision medicine in myelofibrosis (MF) has moved beyond confirmation of a driver mutation toward an integrated interpretation of marrow morphology, molecular profile, cytogenetics, clinical phenotype, symptom burden, and transplant fitness. Myelofibrosis is biologically heterogeneous across both primary MF and secondary MF arising after polycythemia vera or essential thrombocythemia, with clinically relevant differences in disease origin, driver distribution, prognostic model validation, phenotype, and outcome. Several prognostic tools and much of the strongest molecular-risk evidence remain best validated in primary MF cohorts; therefore, PMF-derived molecular signals should be applied cautiously to secondary MF, where MYSEC-PM and disease-origin-specific interpretation are more appropriate. Current precision care is actionable now in diagnosis, integrated risk assessment, phenotype-adapted JAK inhibitor selection, structured symptom assessment, and transplant timing. Ruxolitinib remains the anchor first-line option for symptomatic proliferative disease; fedratinib provides an alternative or post-ruxolitinib option in selected patients with preserved platelet reserve; pacritinib is particularly relevant in severe thrombocytopenia; and momelotinib has a differentiated role in anemia-dominant MF. Allogeneic hematopoietic cell transplantation remains the only curative strategy and should be discussed early for biologically or clinically high-risk disease. Emerging artificial intelligence (AI) applications in digital pathology, prognostic modeling, and post-transplant prediction may further operationalize precision care, but they remain adjunctive rather than autonomous and require external validation, explainability, governance, and human oversight before routine deployment. This review reframes MF through an MF-specific precision-medicine lens centered on biology, patient selection, phenotype-adapted treatment, transplantation, monitoring, and the boundary between what is currently actionable and what remains investigational.

Multiple myeloma (MM) is a hematologic malignancy characterized by the clonal proliferation of plasma cells, resulting in considerable morbidity and mortality. Although therapeutic advancements have improved clinical outcomes, this has been restricted to some high-income nations. Countries in the Gulf region, despite significant rises in gross domestic product (GDP), have resource-constrained environments and hence face unique challenges when it comes to the management of MM mainly because of the limited spending on healthcare (as a percentage of the GDP) in these countries. This narrative analysis explores the epidemiology, patient demographics, and therapeutic landscape of relapsed and refractory multiple myeloma (RRMM) in Gulf nations, including the United Arab Emirates (UAE), Qatar, Bahrain, Kuwait, and Oman. Our findings emphasize the growing incidence of MM in the region, with increased mortality rates owing to delayed diagnosis, restricted access to some of the advanced medicines in few areas, and disparities in care. Patients in the Gulf countries usually present at a younger age than their global counterparts, with median ages of diagnosis ranging from 43 to 58 years. Access to innovative treatments like CAR T-cell therapy and bispecific antibodies has been limited by high costs and infrastructural barriers. Stem-cell transplantation, although available in most countries, is insufficiently utilized, and treatment approaches frequently depend on conventional medicines. Obstacles to prompt diagnosis, difficulty in accessing treatment centers, limited availability of innovative treatment, and inadequate regional monitoring protocols, impede efficient illness management. Insights from the Gulf MM Advisory Board highlight the need for individualized treatment protocols, enhanced accessibility to novel treatments, and improvements in healthcare infrastructure. Cooperative initiatives among healthcare professionals, decision makers, and industry stakeholders are crucial for formulating regional treatment protocols and enhancing clinical trial networks. Reflecting on these shortcomings will be critical to improving patient outcomes and aligning MM care in the Gulf region with international standards.

Hyperhemolysis syndrome (HHS) is a rare but severe complication of red blood cell transfusion, characterized by the destruction of both the patient’s and donor’s red blood cells. This condition results in post-transfusion hemoglobin levels lower than pre-transfusion levels, often leading to profound anemia, tissue ischemia, and multiorgan failure. HHS predominantly affects individuals with hemoglobinopathies, particularly sickle cell disease. While the pathophysiology remains poorly understood, proposed mechanisms include bystander hemolysis via complement activation, suppression of erythropoiesis, macrophage-mediated RBC destruction. Refractory cases of HHS are managed with Eculizumab and Tocilizumab, targeting the complement pathway and macrophage activation, respectively. This review analyzed 22 reported cases of HHS identified through PubMed, Embase, and Google Scholar. Of these, 11 patients received Eculizumab, 10 received Tocilizumab, and 1 received both. The cohort had an mean age of 29.5 years, with 36.4% male and 63.6% female. Most patients had underlying hemoglobinopathies. Outcomes showed improvement in 18 patients without major side effects, while 1 patient showed no improvement, and 3 patients passed away. Despite promising results, concurrent use of other immune-modulating agents during treatment complicates attributing the observed efficacy to specific medications alone. Further studies are required to further evaluate the pathophysiology of HHS and assess the safety and effectiveness of these novel therapies.