Journal of Blood Medicine最新文献

Sickle cell disease (SCD) is an inherited haemoglobinopathy caused by a point mutation in the β-globin gene, resulting in abnormal sickle haemoglobin (HbS) and variable clinical expression ranging from mild to severe. While individuals with sickle cell trait are usually asymptomatic, those with homozygous disease may experience chronic haemolytic anaemia, recurrent vaso-occlusive crises, and progressive organ injury. Current standards of care, including hydroxyurea therapy, chronic blood transfusions, and allogeneic haematopoietic stem cell transplantation (HSCT), have substantially improved survival and reduced complications. However, each approach has limitations, such as incomplete disease control, toxicity, and limited donor availability. Recent advances in non-myeloablative and haploidentical HSCT have expanded curative options, achieving high survival with minimal graft-versus-host disease, though accessibility and cost remain challenges. Emerging gene therapies, particularly lentiviral vector-mediated gene addition and CRISPR-Cas9 genome editing, represent major progress by directly targeting the underlying genetic defect. These autologous approaches eliminate donor-related immune risks and have demonstrated durable haemoglobin correction, near-complete resolution of vaso-occlusive events, and encouraging outcomes in stroke prevention. This review synthesises evidence comparing gene therapies with standard treatments, outlining molecular mechanisms, efficacy, safety, and long-term considerations. Key challenges include stem-cell mobilisation, fertility preservation, conditioning toxicity, and equitable access. Early trials show substantial clinical benefit, improved quality of life, and favourable safety profiles. Emerging in vivo editing technologies may further simplify delivery and enhance global accessibility. Integrating gene therapy into evolving standards of care could transform SCD management, offering realistic prospects for durable remission or cure.

Background: The dynamic changes of the hematopoietic system during fetal development may be disrupted by preterm birth. Hematopoietic stem and progenitor cell (CD34⁺) levels are poorly investigated in preterm infants, particularly in relation to immune responses and morbidities. This is partly because of low blood volumes, which raise ethical concerns and limit specific sampling for research studies. To overcome this problem, we used residual blood from routine clinical testing to monitor CD34⁺ cell counts in the first months of life. Our aim was to characterize the dynamics of circulating CD34⁺ cells and explore associations with prenatal and postnatal clinical events.

Methods: We retrieved residual blood samples from nine infants born <28 weeks gestational age (GA), collected from birth through eight postnatal weeks. CD34⁺ cell count was assessed using flow cytometry. The number of nucleated red and white blood cells, and hemoglobin concentration were also measured.

Results: Median (min-max) GA was 25+0 (22+3─27+5) weeks. CD34⁺ cell counts at birth ranged from 19 to 284 x 10⁶ cells/L. Between days 0 and 1, CD34⁺ cell count increased in four infants and decreased in four. By day 7, the proportion of CD34⁺ of total nucleated blood cells was significantly lower than at birth (p=0.018). High inter- and intra-individual variability in CD34⁺ cell count was observed. Notably, the highest CD34⁺ cell levels coincided with maternal or infant infections.

Conclusion: This pilot study demonstrates the feasibility of longitudinal monitoring of CD34⁺ hematopoietic stem and progenitor cells in extremely preterm infants using residual clinical blood samples. While limited by a small sample size, the study provides preliminary insights into early immune function and highlights directions for future research in larger cohorts.

Background: A major challenge after allogeneic haematopoietic stem cell transplantation for haematologic malignancies is the management of acute graft-versus-host disease (aGVHD), which remains associated with poor prognosis despite therapeutic advancements. We conducted a randomized, double-blinded, placebo-controlled Phase I/II clinical trial to assess the safety and efficacy of umbilical cord-derived mesenchymal stem cells (Cyto-MSC) as an upfront treatment in patients with grade II-IV aGVHD.

Methods: In this multicentre trial, 22 grade II-IV aGVHD patients were randomized to receive up to three infusions of Cyto-MSC (n = 14) or placebo (n = 8), alongside standard corticosteroid therapy. The primary endpoints were overall response (OR) at Day 28 and overall survival (OS) at 12 months. The secondary endpoints included correlation between responses at Day 28 with 12-month OS and exploratory analyses of immune cell subsets.

Results: No treatment-related adverse events were observed. There were no significant differences between Cyto-MSC and placebo in the OR at Day 28 and 12-month OS. Among patients with severe grade III-IV aGVHD who achieved OR by Day 28, those treated with Cyto-MSC had significantly improved 12-month OS compared to placebo (100% vs 50%, p=0.039). Furthermore, in patients with severe aGVHD and baseline CD4⁺ T_EMRA >35% or CD8⁺ T_EMRA >70%, the survival benefit was pronounced in the Cyto-MSC group (83.3% and 100%, respectively). In contrast, none of the placebo-treated patients with baseline CD4⁺ T_EMRA <35% (p=0.007) or CD8⁺ T_EMRA <70% (p=0.005) survived at 12 months. OS was significantly associated with OR at Day 28 (p<0.001), baseline CD4⁺ T_EMRA (p=0.004), and baseline CD8⁺ T_EMRA (p=0.004).

Conclusion: Patients with severe grade III-IV aGVHD, particularly those who respond early or have elevated baseline CD4⁺ T_EMRA (>35%) or CD8⁺ T_EMRA (>70%) levels, may have an overall survival advantage when treated with Cyto-MSC as an upfront therapy in combination with standard corticosteroids.

Aim: Alloimmunization (the production of antibodies against foreign red blood cell (RBC) antigens) is a significant complication in patients with sickle cell disease (SCD) who require chronic transfusion. This retrospective study examined the distribution of ABO and Rh phenotypes in SCD patients at Dr. Soliman Fakeeh Hospital in Jeddah (DSFH-J) and their implications for alloimmunization risk. The high immunogenicity of the K antigen in the Kell system, second only to that of the D antigen in the Rh system, makes it a frequent target.

Results: Among 241 patients with SCD, the most common blood group was O (58.5%), followed by A (26.97%), B (12.03%), and AB (2.9%). The majority of patients (93.36%) were Rh-positive (D antigen-present). Among Rh antigens, the e antigen was the most prevalent (97.51%), while C antigen and c antigen were detected in 68.04% and 75.52% of patients, respectively. Within the Kell system, K was found in 8.29% of the study population. The most common antibodies detected were anti-E (20%) and anti-C (15%), indicating Rh incompatibilities to be a major concern. Kell system antibodies (anti-K) accounted for 12.5% of cases, and unidentified alloantibodies represented 17.5%. Although antibodies from other blood group systems (such as Kidd, Duffy, Lutheran, and MNS) were detected at low frequencies, their presence and known clinical significance in causing transfusion reactions underscore the need for extended RBC phenotyping to include these systems.

Conclusion: The observed distribution of Rh phenotypes and the presence of alloantibodies beyond the prevalent ones highlights the need for extended RBC phenotyping to include other blood group systems, such as Kidd and Duffy. Establishing a national blood donor registry with comprehensive RBC antigen data is a crucial step toward ensuring safer transfusions. Standardizing blood screening protocols across hospitals in Saudi Arabia and introducing routine extended RBC typing before transfusions would minimize alloimmunization risks and improve the overall patient safety.

Introduction: In Europe, recombinant von Willebrand factor (rVWF) is approved for the prevention and treatment of hemorrhage or surgical bleeding in adults with von Willebrand disease (VWD) for whom desmopressin alone is ineffective or contraindicated. Real-world data on rVWF safety are limited.

Aim: To assess the safety of rVWF in real-world European clinical practice.

Methods: EU post-authorization safety study (NCT05265078, EUPAS45617) was a multicenter, retrospective, non-interventional study conducted in adults with VWD who received rVWF at 1 of 30 participating sites in Europe (January 2019-March 2023). Data were collected retrospectively for ≥7 days and ≤6 months after the first rVWF infusion, and similarly, after each subsequent rVWF course. Primary outcomes were the risk of hypersensitivity reactions, thromboembolic events, and VWF/factor VIII (FVIII) inhibitor formation when used for hemorrhage treatment or prevention/treatment of surgical bleeding; and the association of thromboembolic events with concurrent use of FVIII for hemorrhage treatment or prevention/treatment of surgical bleeding.

Results: In the primary analysis, 87 patients received 203 rVWF treatment courses. In total, 2 hypersensitivity-related AEs of mild severity occurred in 1 patient who received rVWF (0.00068 events per person-day at risk), and 1 thromboembolic AE of moderate severity (venous thrombosis) was reported in 1 patient (0.00127 events per person-week at risk). There were no reports of VWF or FVIII inhibitor formation. The association between thromboembolic events and the concurrent use of rVWF and FVIII could not be assessed because no patient received rVWF in conjunction with FVIII.

Conclusion: In this EU post-authorization safety study, the risks of hypersensitivity reactions and thromboembolic events with rVWF were low and there were no reports of VWF or FVIII inhibitor formation. Overall, no new safety signals were identified in this European real-world study when rVWF was used for the prevention or treatment of hemorrhage or surgical bleeding in VWD.

Non-traumatic fat embolism syndrome (FES) in sickle cell disease (SCD) is associated with high morbidity and mortality. This severe complication arises from bone marrow necrosis, which subsequently can lead to fat embolism syndrome and multi-organ failure. A key challenge in diagnosing and managing this syndrome lies in the absence of established diagnostic criteria and the variability of its clinical presentation. Instant red cell exchange transfusion could be lifesaving once the syndrome is suspected, and the use of therapeutic plasma exchange, as suggested in the literature, can improve outcomes. Here, we report two cases of SCD with FES that were managed successfully with blood transfusion and plasma exchange. Both of them rapidly deteriorated and required intensive care unit admission, where they received red cell exchange followed by plasma exchange. They both made a good recovery and were discharged from the hospital within two weeks.

Background: β-thalassemia major (βTM) is a severe genetic blood disorder that necessitates regular blood transfusions, which often lead to iron overload and associated complications, including liver dysfunction and dyslipidemia.

Objective: To investigate the relationship between iron overload, liver function abnormalities, and lipid profile disturbances in transfusion-dependent β-thalassemia patients in Sana'a, Yemen.

Methods: A cross-sectional study was conducted among 53 participants recruited from the Yemeni Association for Thalassemia Patients and Genetic Blood Disorders in Sana'a City. Participants were divided into four groups: healthy controls, β-thalassemia patients receiving regular blood transfusions with or without iron chelation therapy (ICT), and nontrans fused thalassemia patients. Clinical data were collected using structured questionnaires, and Biochemical and haematological parameters, including serum ferritin, serum iron, GPT (ALT), bilirubin, triglycerides (TG), HDL, LDL, cholesterol, hemoglobin (Hb), and white blood cell (WBC) counts, were measured. The data were analyzed using SPSS Version 20. Normality was assessed with the ShapiroWilk test. Parametric tests, including independent sample ttests and ANOVA, were used to compare continuous variables. Categorical data were analyzed with the chi-square test. A Bonferroni correction was applied to adjust for multiple comparisons.

Results: Serum ferritin levels above 1,000 ng/mL were considered elevated, and iron levels were significantly higher in transfusion-dependent patients, particularly those receiving blood for >5 years or >250 mL per transfusion. Group II (patients receiving blood transfusions with ICT) and Group III (patients receiving blood transfusions without ICT) showed significantly elevated ferritin and serum iron levels compared to Group IV (non-transfused patients). Patients with high ferritin levels also exhibited significantly elevated GPT and direct bilirubin, indicating liver damage, with the highest levels observed in Group II and Group III. Furthermore, these patients had higher triglycerides and lower HDL, LDL, and total cholesterol, consistent with dyslipidemia. Haematological parameters showed reduced hemoglobin and RBCs, and increased WBCs among patients with iron overload.

Conclusion: Iron overload is strongly associated with liver dysfunction and dyslipidemia in transfusion-dependent β-thalassemia patients. The findings suggest that iron chelation therapy helps reduce the impact of iron overload on liver function and lipid metabolism. Routine monitoring of ferritin, liver enzymes, and lipid profiles is essential for managing these complications. Effective iron chelation therapy is critical, and improving access to ICT and establishing better follow-up strategies are needed to mitigate the long-term consequences of iron overload.

Introduction: Haemophilia, an X-linked recessive bleeding disorder caused by mutations in the F8 and F9 genes, remains profoundly underdiagnosed in resource-limited settings. In Tanzania, it is estimated that fewer than 10% of individuals with haemophilia are diagnosed. Centralized services, limited diagnostic capacity, and underutilization of available therapies pose major barriers to timely and effective care. This review reports on the activities undertaken to establish and expand haemophilia care in Tanzania, charting the journey toward excellence.

Methods: This is a comprehensive review of national program reports, registry data from the Haemophilia Society of Tanzania, and interviews with key personnel directly involved in the development of haemophilia services between 2021 and April 2025.

Results: Between 2021 and 2025, Tanzania made significant strides in strengthening haemophilia care. A multidisciplinary workforce was trained both locally and internationally in specialized diagnosis, treatment, and management of haemophilia and other inherited bleeding disorders. Fourteen haemophilia clinics were established, including a national comprehensive clinic at Muhimbili National Hospital and satellite clinics across zonal and regional hospitals, providing screening, diagnosis, and comprehensive care. As of 17th April 2025, a total of 473 patients had been registered and were receiving structured care through this network.

Conclusion: The integration of specialized haematological training, stakeholder engagement, decentralization of services through 14 clinics, and the development of a national registry and clinical guidelines have markedly enhanced Tanzania's capacity to diagnose and manage haemophilia and other inherited bleeding disorders. Moving forward, it is imperative to expand regional coverage, intensify community-based awareness and screening initiatives, strengthen capacity building and research efforts, and establish a specialized centre of excellence dedicated to advancing haemophilia care, professional training, research, and innovation.

Background: Vitamin B12 (cobalamin) deficiency is a well-known cause of hematologic and neurological disorders; however, its presentation can be highly variable, leading to diagnostic challenges. The etiology is diverse: while the most common cause is dietary insufficiency, other potential causes include malabsorption syndromes, autoimmune gastritis, gastrointestinal disorders, chronic infections, and genetic defects. Clinical presentation varies significantly, ranging from clinically silent macrocytosis to life-threatening anemia or pancytopenia. Neurological and psychiatric manifestations may include vision and gait impairment, depression, and cognitive dysfunction. Given this complexity, vitamin B12 deficiency can mimic other conditions, often leading to a delay in diagnosis.

Case presentation: A 15-year-old male was admitted in critical condition with severe anemia, thrombocytopenia, jaundice, progressive weight loss, fatigue, gait disturbances, and vision impairment. Initially, Evan's syndrome was suspected, but further laboratory investigations, including a peripheral blood smear and elevated mean corpuscular volume (MCV), led to the diagnosis of profound vitamin B12 deficiency. Additional workup revealed chronic atrophic gastritis as the underlying cause. The patient was treated with vitamin B12 injections, leading to significant hematologic and neurological improvement, weight gain, and resolution of psychiatric symptoms. However, optic nerve atrophy was detected as a late complication.

Conclusion: This case emphasizes the need to consider vitamin B12 deficiency in pediatric patients with unexplained hematologic, neurological, and psychiatric symptoms, particularly when associated with chronic atrophic gastritis. Early recognition and intervention are crucial to preventing irreversible complications, such as optic neuropathy. Given the multidisciplinary nature of its presentation, this case serves as an important reminder for pediatricians, hematologists, gastroenterologists, and neurologists to maintain a high index of suspicion for vitamin B12 deficiency in complex clinical scenarios.

Herpes simplex virus (HSV) infection is a common problem in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Severe HSV infections can cause pneumonia, encephalitis, meningitis and other lesions, thus requiring caution. Acyclovir is the drug of choice for the prevention of HSV infection. Acyclovir resistance caused refractory HSV infection which is a severe complication after allo-HSCT. Cidofovir may be effective for acyclovir-resistant patients; however, the efficacy of systemic cidofovir administration for acyclovir-resistant patients after allo-HSCT remains unknown. We describe a 67-year-old female patient with multiple ulcers and erosions of the periocular, perioral, and oral mucosa after haploidentical allo-HSCT. Poor results were observed after the treatment of acyclovir and foscarnet. In particular, an adverse effect of low potassium and renal damage has been observed with foscarnet. Genetic testing suggested an acyclovir-resistant herpes simplex virus type 1 (HSV1) infection with T287M mutation of gene UL23. The patient's infection was cured after intravenous treatment with cidofovir. Systemic administration of cidofovir may be useful for patients with acyclovir-resistant HSV1 infection after haploidentical allo-HSCT.