Annals of Hematology最新文献

Castleman disease (CD), a rare and clinically heterogeneous condition, frequently involves renal impairment, though this relationship remains poorly characterized. This large cohort study of 183 patients (116 unicentric [UCD], 67 multicentric [MCD]) investigated renal involvement (RI). RI occurred in 6.03% (7/116) of UCD and 55.22% (37/67) of MCD patients. In UCD-RI, 4 underwent renal biopsy, revealing varied pathological results, and 1 underwent total left nephroureterectomy. In MCD-RI, common manifestations included edema, nephrotic syndrome, and acute renal failure. Thrombotic microangiopathy (TMA) was the most frequent renal pathology (9/19 biopsies). Acute renal failure often responded well to treatment, with 60% (9/15) achieving complete recovery. The myeloma-like treatment regimen demonstrated superior efficacy compared to the lymphoma-like regimen and immunomodulatory therapy (P = 0.039). The 5-year renal survival rate in the MCD-RI group was 88.9%, not significantly different from UCD-RI (P = 0.45). Furthermore, the 5-year overall survival in the CD-RI group was 81.9%, showing no statistically significant difference from CD patients without renal involvement (P = 0.11). This study confirms that RI is more common in MCD, with TMA as a key pathological feature, and demonstrates that renal involvement does not negatively impact overall survival.

Angioimmunoblastic T-cell lymphoma (AITL) is a subtype of peripheral T-cell lymphoma originating from follicular helper T cells and characterized by profound clinical, pathological, and molecular heterogeneity. Despite advances in classification and diagnosis, therapeutic outcomes remain suboptimal, particularly in relapsed or refractory settings. In recent years, the evolution of risk stratification models and a deeper understanding of AITL’s molecular pathogenesis, including its unique pattern of clonal evolution, have paved the way for precision medicine. Notably, targeted treatment approaches, such as immunomodulatory agents, epigenetic therapies, kinase inhibitors, and immune checkpoint blockade, are demonstrating promising clinical efficacy, especially in patients harboring specific molecular aberrations. This review comprehensively summarizes the multilayered heterogeneity of AITL, emphasizes the role of immune and molecular profiling in informing therapeutic decisions, and outlines future directions for personalized, multi-agent treatment strategies aimed at overcoming resistance and improving survival.

Acute myeloid leukemia (AML) is a high-risk hematologic malignancy with poor long-term survival and frequent relapse, sustained by leukemic stem cells, antigenic heterogeneity, and an immunosuppressive bone marrow niche. Although chimeric antigen receptor (CAR) T-cell therapy achieves durable responses in B-cell malignancies, its application in AML is restricted by on-target myelotoxicity from antigen overlap with normal progenitors, heterogeneous and dynamic antigen expression, rapid T-cell exhaustion in suppressive microenvironments, limited manufacturing windows with compromised T-cell quality, and uncertainty in optimal infusion timing. To address these barriers, logic-gated and adapter CARs are engineered to broaden antigen recognition while limiting toxicity; nanobody-based CARs provide stable, low-immunogenic binding; gene-edited hematopoietic stem and progenitor cells permit AML clearance without prolonged marrow suppression; and metabolic or epigenetic modulation is employed to sustain T-cell function in hostile niches. Allogeneic CAR-T platforms offer a potential means to overcome manufacturing constraints and improve treatment accessibility. In selected settings, sequential CAR-T therapy and hematopoietic stem cell transplantation consolidate remission and restore hematopoiesis. This review integrates current and emerging AML antigen targets with engineering innovations into a structured translational framework, directly addressing the biological, manufacturing, and application barriers unique to AML, and outlining strategies with the potential to advance CAR-T therapy from experimental studies to durable clinical benefit.

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by splenomegaly, symptoms, cytopenias, and chronic inflammation. PMF has two stages: pre-fibrotic (prePMF) and overt PMF. PrePMF and essential thrombocythemia share a similar high thrombotic risk, but few studies have examined thrombosis risk factors in prePMF. The neutrophil-to-lymphocyte ratio (NLR), reflecting the imbalance between systemic inflammation and immunity, has emerged as a prognostic biomarker in various diseases. We investigated the predictive value of NLR for thrombotic risk in a multicenter cohort of 225 prePMF patients enrolled in the retro-prospective observational INFLA-ME (INFLAmmation in MyeloproliferativE disease) cooperative study. After a median follow-up of 5.9 years, 37 thrombotic events occurred in 31 patients (2.5 events/100 patients/year; 18 arterial, 19 venous). Multivariate analysis linked venous thrombosis risk to prior venous events (HR 4.46, p = 0.001) and NLR ≥ 6 (HR 3.82, p = 0.008). The patients with NLR ≥ 6 showed a shorter venous thrombosis-free survival (p = 0.003). NLR value had no significant association with total and arterial thrombotic events. In conclusion, NLR is an inexpensive and accessible prognostic biomarker of venous thrombosis in prePMF. The integration of NLR into conventional risk scores may allow for better identification of pre-PMF patients requiring cytoreduction.

As a novel multiple myeloma (MM) specific antigen, rare is known about the underlying molecular mechanism of MMSA-1 gene in the progression of myeloma. Transcription factor 4 (TCF4) and MMSA-1 over/down expressed stable U266 cell lines was constructed using lentivirus transfection technique. TCF4’s impact on MMSA-1 expression was explored. Overexpressed of MMSA-1’s interaction with RAS protein and its downstream signaling pathways was investigated. Moreover, the interaction changes between overexpressed MMSA-1 protein and bone marrow microenvironment were also detected by examing adhesion molecules and angiogenesis promoting factors using Western Blot. We successfully constructed transcription factor 4 (TCF4) and MMSA-1 over/down expressed stable U266 cell lines (termed ^TCF4−/+U266 and ^{MMSA−1−/+}U266). Our result showed that TCF4 could bind with MMSA-1 promoter sequence, greatly up regulate its promotor activity and then improve MMSA-1 expression. Overexpressed MMSA-1 also made a series of changes in U266 cells, including promoting RAS protein expression in cytoplasm, enhancing the interaction between MMSA-1 and RAS, which resulted in hyperactivation of RAS and its downstream signaling pathways including RAF/MEK/ERK and RAF/PI3K/AKT, improving U266 cells’ clonogenicity capacity, changing apoptosis related proteins, reducing the interaction between myeloma cell and bone marrow microenvironment by reducing adhesion molecules expression including HIF-1α, E-cadherin, CXCR4 expression and elevating angiogenesis promoting factors including VEGF, Ang-2 and reducing Ang-1 at the same time. These results suggested MMSA-1 was over expressed in MM cells being regulated by Wnt/β-catenin/TCF4 signaling pathway, which resulted in hyperactivation of downstream RAS/RAF signaling pathway and eventually promote myeloma cells survival and invasion.

This study aimed to investigate the prognostic value of FLT3-ITD molecular features such as allelic ratio (AR), variant allele frequency (VAF), insertion length, insertion number and insertion site in patients with de novo acute myeloid leukemia (AML). Next-generation sequencing (NGS) was used to detect FLT3-ITD mutations in 170 patients with newly diagnosed AML (except acute promyelocytic leukemia). FLT3-ITD patients with longer insertion lengths, higher allelic ratio, and more mutations had relatively shorter overall survival(OS), though not statistically significant. Early transplantation or FLT3 inhibitor therapy led to longer OS and event-free survival(EFS). Insertion sites located in Hinge Region(HR)/β1 domain and juxtamembrane domain (JMD) derived significantly greater benefit from early FLT3 inhibitor therapy(primarily sorafenib), showing significantly prolonged overall survival. HR/β1 insertion and multiple insertions showed a trend toward being risk factors for EFS. While white blood cell count > 30 × 10⁹/L and insertion of FLT3-ITD in the HR/β1 site were independent risk factors affecting patients’ overall survival. Patients with high white blood cell counts and HR/β1 insertions demonstrated shorter overall survival, while early administration of FLT3 inhibitors resulted in significantly prolonged overall survival in this population. Early transplantation and FLT3 inhibitor therapy significantly improved prognosis in AML patients. In the era of FLT3-ITD targeted drug therapy combined with transplantation, the insertion site of FLT3-ITD based on high throughput sequencing results helps predict the efficacy of FLT3 inhibitors. Integrating white blood cell count with HR/β1 insertion site can identify a high-risk patient subgroup likely to benefit from FLT3 inhibitor therapy.

Polycythemia vera (PV) is a myeloproliferative neoplasm. The presence of JAK2 mutations is a major diagnostic criterion for PV. PV is linked to chronic inflammation and an increased risk of thrombosis, and inflammation plays a significant part in the pathophysiology of PV. Testing for JAK2 mutations is expensive and is not available in all laboratories. Simple inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), are evaluated in this study as potential diagnostic markers for differentiating patients with PV from other patients with polycythemia. We conducted a retrospective study of the clinical and laboratory data from 281 patients with polycythemia (110 with PV and 181 with secondary polycythemia (SP)) who attended Ghaem Hospital. The diagnosis of PV was established based on the World Health Organization criteria. Individuals who did not meet the criteria were classified as having SP. The median NLR, PLR, and SII in the PV group were considerably elevated compared to the SP group (NLR: 5.00 vs. 1.86, PLR: 261.3 vs. 94.0, SII: 2432.9 vs. 368.8, p < 0.001 for all). The receiver operating characteristic analysis revealed that NLR, PLR, and SII were highly effective in differentiating PV patients from the SP group. Each of these tests showed sensitivities and specificities over 85% and an area under the curve of more than 0.9. SII, NLR, and PLR were all higher in PV than SP, suggesting that these biomarkers, particularly SII, might be helpful in the diagnosis of PV.

Platelet transfusion is a cornerstone of modern supportive care, yet its application is characterized by significant practice variation and uncertainty regarding optimal strategies. This comprehensive review synthesizes current evidence to delineate a more nuanced, physiologically informed approach to platelet therapy. A paradigm shift is underway, moving from uniform count-based triggers toward more restrictive, evidence-based practices; this includes prophylactic thresholds of < 10 × 10⁹/L in stable hematology-oncology patients and therapeutic-only strategies in select populations. In massive hemorrhage, fixed-ratio resuscitation protocols incorporating early platelet administration are critical for improving hemostasis. Conversely, high-quality evidence now defines populations where transfusion may be harmful, including in thrombotic microangiopathies like TTP, heparin-induced thrombocytopenia, and spontaneous intracerebral hemorrhage in patients on antiplatelet agents. The utility of viscoelastic assays in guiding goal-directed therapy and the potential of novel products such as pathogen-reduced, cold-stored, and cryopreserved platelets to mitigate the limitations of conventional storage are also critically examined. This review provides clinicians with a framework to navigate these complexities, emphasizing a context-dependent strategy that balances hemostatic benefit against potential harm to optimize patient outcomes and steward a precious resource.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare hematologic malignancy with an aggressive course and poor prognosis. Treatment remains challenging particularly in patients who are ineligible for stem cell transplantation due to resistance to conventional chemotherapy. The introduction of tagraxofusp, a CD123-directed cytotoxin, has significantly expanded therapeutic options and improved outcomes for patients with BPDCN. However, its use can be accompanied by notable adverse events, especially capillary leak syndrome, underscoring the need for careful patient selection and monitoring. Up to date, no data is available regarding the safety of tagraxofusp in patients with chronic kidney failure and cardiovascular co-morbidities. We present the case of a 79-year-old male who developed a solitary, rapidly progressing skin lesion on his lower back. The lesion represented the first manifestation of BPDCN with bone marrow infiltration and concomitant myelodysplastic syndrome (MDS). Molecular analysis identified mutations in CBL, TET2, ZRSR2 and KRAS. Non-eligible for stem cell transplantation, the patient was admitted to treatment with tagraxofusp in a dose-reduced protocol due to concomitant chronic kidney disease (CKD). After three doses of the first cycle, treatment needed to be stopped due to acute-on-chronic renal failure. After treatment disruption, kidney failure was completely restituted to pre-treatment levels. Notably, skin and bone marrow biopsies demonstrated a dermatologic complete response and partial remission of bone marrow infiltration. A watch and wait concept was followed, and prolonged therapy response was obtained for 8 months before relapse. To our knowledge, this is the first reported case demonstrating the use of tagraxofusp in a patient with BPDCN and advanced chronic kidney disease, showing that even a minimum of tolerated treatment dose can induce a sustained response. Despite the risk of adverse events, tagraxofusp should be considered a viable treatment option for elderly patients with poor performance status and significant comorbidities who are ineligible for intensive chemotherapy or stem cell transplantation, as even limited exposure may achieve meaningful clinical responses.