Hematology最新文献

Objectives: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare condition characterized by intravascular hemolysis (IVH), thrombosis, and organ damage. Although C5 complement inhibitors such as eculizumab have significantly improved the prognosis of patients with PNH, persistent anemia remains in some patients.

Methods: We report a patient with PNH who initially responded to eculizumab but experienced recurrent hemoglobin decrease and became transfusion-dependent after 24 weeks of treatment. Here, we present the clinical features of this patient. In addition, we reviewed the current literature to characterize persistent anemia caused by non-dominant residual IVH following C5 inhibitor therapy in PNH, along with related biomarker assessment and clinical applications of proximal complement inhibitors.

Results: Lactate dehydrogenase (LDH) levels did not significantly increase, and the direct antiglobulin test (DAT) with anti-C3d was only weakly positive (titre 1:16). The changes in free hemoglobin, haptoglobin, and type III red blood cells (RBC) (total loss of CD59) indicated subclinical yet active IVH. After the introduction of iptacopan monotherapy for six weeks, the levels of LDH, free hemoglobin, and haptoglobin normalized, and the need for further transfusions was eliminated. The proportion of type III RBC increased to 57.3%.

Conclusion: This case suggests that persistent anemia in patients with PNH following C5 inhibitor therapy might be associated with subclinically active IVH, and proximal complement inhibitors, such as iptacopan, may offer effective management of this condition.

Objectives: Systemic iron overload in transfusion-dependent anemias leads to progressive myocardial iron accumulation, a major cause of morbidity and mortality. This study evaluated the relationship between cardiac T2* magnetic resonance imaging (MRI) values and natriuretic peptide levels in patients with systemic iron overload.

Methods: Cardiac T2* MRI magnetic resonance imaging (MRI) is the gold standard for assessing myocardial iron, but it is costly and not widely available. B-type natriuretic peptides (BNP and NT-proBNP), which reflect myocardial stress, may offer a practical biomarker alternative. This systematic review and meta-analysis evaluated the relationship between cardiac T2* MRI values and natriuretic peptide levels in patients with systemic iron overload. Nine studies involving 783 patients were included in the systematic review, and pooled analyses were performed using data from seven studies.

Results: Pooled data from seven studies showed a moderate inverse correlation between T2* values and natriuretic peptide levels (r = -0.30, 95% CI -0.51 to -0.06), indicating higher peptide levels with greater myocardial iron deposition. Patients with cardiac iron overload (T2* < 20 ms) had significantly higher peptide levels (standardized mean difference = -0.71, 95% CI -1.32 to -0.11), with pooled mean concentrations of 321.1 (95% CI 248.3-393.9) compared with 179.0 (95% CI 134.3-223.6) in those without cardiac iron overload (T2* > 20 ms).

Discussion: These findings suggest that natriuretic peptide levels reflect myocardial stress associated with cardiac iron burden and may provide clinically relevant information on myocardial iron overload.

Conclusion: Although natriuretic peptides cannot replace cardiac MRI, they may serve as accessible, low-cost adjunct biomarkers for screening, monitoring, and early warning of myocardial iron overload, particularly where MRI is limited. Further prospective studies are warranted to validate their role in longitudinal assessment and risk prediction.

Objectives: The aim of this study was to assess the burden of Burkitt lymphoma (BL) at the global, regional, and national levels from 1990-2021 and to project trends over the next 15 years.

Methods: Data from the 2021 Global Burden of Disease database was used for analysis.

Results: Both the incidence and prevalence rates of BL increased from 1990-2021. BL demonstrated a bimodal age pattern, with incidence peaking among children aged 5-9 years and again in adults older than 65 years. The disease burden was consistently greater in males than in females. A significant positive correlation was found between the sociodemographic index (SDI) and both the incidence and prevalence rates, whereas the mortality and DALY rates were significantly negatively correlated with the SDI. Health inequality analyses revealed that while incidence and prevalence burdens have increasingly concentrated in high-SDI countries, mortality and DALY burdens remain disproportionately higher in low-SDI regions. Frontier analysis demonstrated that in most countries, BL-related DALYs remain above the expected level on the basis of development status. The projected trend shows a slow but continuous decline in global BL age-standardized rates through 2036.

Conclusions: Over the past three decades, the global burden of BL has steadily increased, accompanied by pronounced regional and sex-related disparities closely associated with levels of sociodemographic development. This comprehensive analysis offers critical insights and evidence-based guidance to inform targeted strategies for the prevention and control of BL worldwide.

Introduction: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare type of cutaneous lymphoma lacking standardized treatments. Consequently, patient outcomes vary significantly.

Methods: This study explored the clinical characteristics and prognostic factors of 205 SPTCL patients from 2000 to 2021 in the Surveillance, Epidemiology, and End Results (SEER) database.

Results: Overall survival (OS) at 1, 3, and 5 years were 78.3%, 75.7%, and 66.4%, respectively. Patients diagnosed after 2008 (possibly excluding the γ-δ subtype) (HR = 0.197, 95% CI = 0.106-0.364, p = 0.000) and Asian or Pacific Islanders (HR = 0.210, 95% CI = 0.049-0.902, p = 0.036) were independent predictors of favorable survival, whereas age 50-60 years (HR = 3.213, 95% CI = 1.357-7.607, p = 0.008) and age > 60 years (HR = 5.039, 95% CI = 2.327-10.911, p = 0.000) were independently associated with poor survival. Patients who received radiotherapy alone exhibited a significantly lower hazard risk compared to those receiving no chemotherapy or radiation (HR = 0.216, 95% CI = 0.048-0.983, p = 0.048). No statistically significant differences in prognosis were observed between patients who received no chemotherapy or radiation and those who received either chemotherapy alone (HR = 1.276, 95% CI = 0.644-2.529, p = 0.485) or radiochemotherapy (HR = 1.283, 95% CI = 0.463-3.558, p = 0.632). These associations persisted after IPTW adjustment, with age, race, year of diagnosis, and treatment remaining independent predictors of OS in SPTCL.

Conclusions: The Ann Arbor staging was not suitable for SPTCL. Radiotherapy represents an appropriate therapeutic option for patients with single or localized skin lesions. No statistically significant differences in prognosis were observed between patients who received no chemotherapy or radiation and those who received either chemotherapy alone or radiochemotherapy. This finding suggests that immunomodulatory agents may be preferable to cytotoxic therapy as initial treatment for SPTCL, an inflammatory lymphoma.

Introduction: Secondary poor graft function (PGF) after autologous hematopoietic stem cell transplantation (Auto-HSCT) for multiple myeloma (MM) is rare, often delayed in recognition, and lacks standardized salvage algorithms.

Areas covered: Using a case-based expert-review format, we summarize diagnostic hallmarks, exclusion work-up, mechanistic drivers, and practical management, with emphasis on autologous stem-cell boost as a rescue option.

Case summary: A 59-year-old woman with IgG κ MM achieved timely neutrophil and platelet engraftment after Auto-HSCT, then developed recurrent transfusion-dependent pancytopenia approximately two months later. Relapse, occult infection/viral reactivation, immune cytopenia, nutritional deficiency, and drug-related myelosuppression were systematically excluded, supporting secondary PGF. Growth factors and thrombopoietin-receptor agonists produced only transient benefit. A second infusion of cryopreserved autologous peripheral blood stem cells (PBSCs) (3.621 × 10⁶ CD34⁺/kg) without re-conditioning led to rapid platelet recovery within 7 days and durable trilineage hematopoiesis.

Expert opinion: Secondary PGF after Auto-HSCT appears multifactorial, involving quantitatively adequate but qualitatively fragile grafts, inflammatory/microenvironmental injury, and therapy-related megakaryocytic vulnerability (including heavy lenalidomide exposure). When backup cells are available and reversible causes are excluded, early unpreconditioned autologous PBSC boost is a safe, feasible, and likely under-utilized salvage strategy. Strategic PBSC banking and early recognition may prevent life-threatening PGF.

Objectives: To elucidate the mechanisms by which leukemia-derived exosomes induce immunosuppression in dendritic cells (DCs) and identify potential therapeutic targets.

Methods: The optimal exosome dosage (20 µg/ml) for DC treatment was determined via gradient concentration experiments. Transcriptomics and qPCR validation explored molecular pathways. DC phenotype was assessed for maturation markers (CD83/CD86), antigen presentation (CD1a), and immune receptors (TLR2). Cytokine levels (IL-6, IL-17, TNF-α, IL-4) were quantified. Multi-omics analysis identified key signaling pathways. Clinical validation utilized samples from AML patients.

Results: Exosome treatment induced broad DC immunosuppression, characterized by significant downregulation of pro-inflammatory cytokines (IL-6, IL-17, TNF-α) and upregulation of anti-inflammatory IL-4. Phenotypic analysis revealed selective inhibition of CD1a and TLR2, while maturation markers (CD83/CD86) remained unaltered. Multi-omics identified TNF-β signaling as the primary immunosuppressive pathway. qPCR confirmed elevated TGF-β2 and mitochondrial ribosomal protein MRPL58, alongside reduced TLR2. Clinical studies in AML patients validated upregulation of TGF-β2, MRPL58, and exosomal markers. Exosomes impaired DC antigen presentation, immune response, and metabolic activity.

Discussion: MRPL58 is a novel mediator of exosome-driven immunosuppression, implicating metabolic reprograming. Selective CD1a/TLR2 inhibition suggests exosomes evade immune detection while permitting DC maturation, a strategy favoring leukemia immune escape. Targeting exosome-DC interactions (e.g. blocking exosomal signals or MRPL58) may restore anti-tumor immunity.

Conclusion: Leukemia exosomes suppress DC function primarily through MRPL58-associated metabolic modulation and TNF-β signaling. MRPL58 represents a promising therapeutic target. Disrupting exosome-mediated immunosuppression could enhance DC-based vaccines and combination immunotherapies for leukemia.

Purpose: This study aims to determine the proportion of bone marrow dysplasia in advance of HIV infection.

Patients and methods: A cross-sectional study was conducted on advanced HIV patients, stage III and IV, with cytopenia at Hasan Sadikin General Hospital, Bandung, from January 2021 to November 2023. Patient characteristics and laboratory data were obtained from patients diagnosed with HIV stages III and IV who presented with cytopenia and underwent bone marrow examinations, as documented in the medical records. The differences between the two groups were analyzed using the Mann-Whitney U test or the Independent T-test for numerical data and Chi-square or Fisher's exact for categorical data.

Results: A total of 42 subjects were enrolled, consisting of 8 (19%) HIV stage III and 34 (81%) stage IV patients. Patients with HIV stage IV exhibited a higher incidence of pancytopenia, with 15 cases (44.1%). The bone marrow cellularity in HIV stage IV was predominantly hypocellular, accounting for 22 cases (64.7%). Dyserythropoiesis was the most common type of bone marrow dysplasia observed in HIV stage IV, present in 19 cases (55.9%). The prevalence of Bone Marrow Dysplasia in HIV stage IV was higher than in HIV stage III, with 23 (64.7%) and 2 (37.5%), respectively (p = 0.2348).

Conclusion: Cytopenias related to HIV are common and tend to worsen as the disease advances. This emphasizes the importance of investigating the potential for bone marrow dysplasia and conducting cytogenetic diagnostic testing for myelodysplastic syndromes (MDS), as a significant non-AIDS-defining hematological malignancy in individuals with advanced HIV.

Background: Secondary acute myeloid leukemia (sAML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor prognosis, but the impact relative to de novo AML remains controversial. We investigated clinical and genetic features in a multicenter Japanese cohort before CPX-351 approval.

Methods: We retrospectively analyzed 294 patients with newly diagnosed AML registered in the Hokkaido Leukemia Net between 2022 and 2023. Propensity score matching was used to adjust baseline variables. Genetic profiles were assessed in 160 matched patients.

Results: In the matched cohort, sAML/AML-MRC did not show inferior overall survival compared with non-sAML/non-AML-MRC (P = 0.90). Adverse karyotypes were the predominant determinant among sAML/AML-MRC. Among sAML/AML-MRC patients, adverse karyotypes were associated with poorer survival than those without adverse karyotypes (P = 0.0075). In contrast, non-sAML/non-AML-MRC groups did not affect survival regardless of adverse karyotypes (P = 0.51). Among 65 patients with ELN 2017 adverse-risk, those with TP53 mutations had markedly shorter survival than those with TP53 wild-type (P = 0.018).

Conclusions: sAML/AML-MRC with an adverse karyotype had a dismal outcome. These findings provide a benchmark for risk stratification in the pre- CPX-351 era.

Background: Congenital thrombocytopenia represents a diagnostically challenging group of disorders due to overlapping clinical presentations among various etiologies.

Case presentation: A 3-month-old infant presented with severe thrombocytopenia (platelet count 6,000/μL), neutropenia, and bone marrow findings of megakaryocytic hypoplasia, initially suggestive of congenital amegakaryocytic thrombocytopenia (CAMT). Comprehensive genetic testing identified a homozygous pathogenic variant in the GNE gene (NM_001128227.2:c.1768G > A, p.Gly590Arg), establishing the definitive diagnosis of GNE-related thrombocytopenia (Thrombocytopenia-12, THC12).

Clinical significance: This case highlights three critical aspects: first, the essential role of genetic testing in differentiating congenital thrombocytopenias; second, the distinct management implications of THC12 compared to CAMT; and third, the need for long-term monitoring given the potential for late-onset myopathy despite initial isolated hematologic manifestations.

Management: Therapeutic interventions included intravenous immunoglobulin, platelet transfusions, and thrombopoietin receptor agonists, with concurrent evaluation for potential hematopoietic stem cell transplantation.

Conclusion: This report underscores THC12 as an important diagnostic consideration in infants with congenital thrombocytopenia and emphasizes the necessity of genetic confirmation to guide appropriate clinical management and family counseling.

Objectives: Dysregulation of apoptosis-related genes (ARGs) may contribute to tumorigenesis and impact patient prognosis, but their specific influence on prognosis and immune characteristics in diffuse large B-cell lymphoma (DLBCL) remains unclear.

Methods: Gene expression profiles were collected from GEO datasets GSE10846 (training set; n = 414) and GSE181063 (validation set; n = 1310), totaling 1724 DLBCL samples. Univariate Cox and LASSO Cox regression analyses were performed to identified key ARGs, which were used to construct a risk score model. Patients were stratified into high/low-risk groups using the risk score. Functional enrichment analyses were conducted to explore biological functions and pathways. Immune cell infiltration was assessed using the CIBERSORT algorithm.

Results: 39 ARGs were significantly associated with overall survival in DLBCL patients. The risk score model effectively stratified patients into high/low-risk groups with distinct survival outcomes. Consensus clustering revealed distinct molecular subtypes with varying prognoses and biological characteristics. Enrichment analyses indicated that the prognostic genes are involved in critical pathways related to apoptosis and immune responses. High-risk patients exhibited higher immune scores and a distinct tumor immune microenvironment.

Conclusion: Apoptosis-related genes are valuable prognostic biomarkers in DLBCL and are associated with distinct immune characteristics. The risk model may aid in personalized risk assessment and inform treatment strategies. These findings provide insights into potential therapeutic targets by modulating apoptosis and immune responses in DLBCL.