Annals of Hematology最新文献

The incidence of paediatric blastic plasmacytoid dendritic cell neoplasm (BPDCN) is extremely low, and little is known about the disease. This study aims to investigate its clinical course and optimal management. We retrospectively analysed the clinical manifestations, laboratory findings, treatment responses, and survival outcomes of 18 paediatric patients with BPDCN treated at our hospital. In this cohort, the male-to-female ratio was 2.6, and the median age of onset was 12 years. Bone marrow involvement was observed in 88.9% of patients (16/18), making it the most commonly affected site, followed by the skin (13/18) and lymph nodes (13/18). Central nervous system infiltration occurred in the youngest patient (Case 13), who experienced relapse after matched sibling donor haematopoietic stem cell transplantation (MSD-HSCT). Immunohistochemical and flow cytometry analyses revealed a distinct immunophenotype, with high expression of CD4 (94.4%), CD56 (100%), CD123 (100%), CD304 (100%), and HLA-DR (100%), and no expression of myeloperoxidase and CD19. In terms of the initial response, 14 patients received acute lymphoblastic leukaemia (ALL)-like regimens, all of whom achieved complete remission (CR) after induction chemotherapy. All 18 patients proceeded to HSCT post-chemotherapy, including 15 haploidentical and 3 MSD transplants. The 4-year overall survival (OS) and event-free survival (EFS) rates for the entire cohort were 94.4% ± 5.4% (95% CI, 83.8%–100.0%) and 87.7% ± 8.2% (95% CI, 71.6%–100.0%), respectively. Paediatric patients with BPDCN who receive allogeneic HSCT—particularly haploidentical HSCT—during CR following ALL-like induction chemotherapy appear to have favorable outcomes in this limited cohort.

Polycythemia vera (PV) and Essential thrombcythemia (ET) are myeloproliferative neoplasms (MPNs) that can progress to secondary myelofibrosis, a complication associated with increased mortality. Circulating CD34-positive cells at diagnosis can be used to distinguish primary myelofibrosis from other MPNs with a threshold of 10/µL. In this study, we evaluate the interest of serial CD34-positive cell quantifications during the follow-up of MPNs. We retrospectively include 180 patients with MPN (90 ET, 55 PV and 35 myelofibrosis) with at least two measurements of circulating CD34-positive cells. CD34-positive cell count showed an AUC of 0.901 for the diagnosis of post-ET/PV myelofibrosis, with a sensitivity of 54.8%, a specificity of 99.5%, a PPV of 89.5% and a NPV of 96.3% for the threshold of 15 cells/µL. The decreased sensibility could be explained by an impact of cytoreductive treatments. Then we focused on primary and secondary myelofibrosis (MF) and found that patients achieving partial or complete response (per IWG-MRT criteria) had lower CD34-positive cell levels. Finally, CD34-positive cell levels had a prognostic impact on overall survival in MF, a count ≥ 100/µL is predictive of a higher risk of death (HR = 2.9 [1.5–5.9]), independently of DIPSS classification. In conclusion, monitoring of circulating CD34-positive cells is valuable for evaluating both disease progression and prognosis in MPN patients.

Acute leukemias of ambiguous lineage (ALAL) is a rare type of hematologic malignancies with poor outcomes. Currently, the treatment for this type of leukemia lack standardized protocols and exhibit significant heterogeneity, necessitating the exploration of novel, targeted approaches. We retrospectively analyzed the clinical characteristics, efficacy, and safety of 13 newly diagnosed Philadelphia chromosome (Ph)-negative ALAL patients between May 2022 and March 2025, who received induction therapy with the mini-CVD regimen (cyclophosphamide, vincristine, dexamethasone) combined with venetoclax and azacitidine. The cohort comprised 8 males and 5 females, with a median age of 53 years (range, 28–73 years). Among this cohort, 92.3% of patients (12/13) achieved complete remission (CR). Three patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) during CR1, and one patient received salvage allo-HSCT following relapse. With a median follow-up of 9.0 months (range 1.2–35.4 months), the overall survival rate was 84.6% (11/13). One patient died due to primary resistance with sustained disease progression, and another succumbed to post-transplantation complications. Of the 12 patients who achieved CR, 2 (15.4%) experienced relapsed, but both attained a second CR after salvage therapy. During induction therapy, the overall incidence of infection was 76.9% (10/13), with the majority being pulmonary infections (5/10). Notably, there was no death during induction therapy. Our data demonstrated that this regimen showed a high CR rate, with manageable toxicity, offering a promising therapeutic approach for this rare and challenging leukemia subtype.

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.