Annals of Hematology最新文献

Background: Thalassemia is an inherited autosomal recessive hematologic disorder characterized by chronic hemolytic anemia due to impaired synthesis of globin chains. A three-level prevention system has effectively reduced the birth rate of affected children and enabled early intervention in Guangxi, China. However, conventional blood tests lack accuracy, and hemoglobin electrophoresis has low predictive value for α-thalassemia with low HbA₂. While genetic testing remains the gold standard, its high-cost limits large-scale use. Thus, a fast, low-cost, and reliable screening method is urgently needed for effective thalassemia control. Methods:An AI-driven detection system for intelligent recognition and quantitative analysis of erythrocyte morphology was developed using a large-scale dataset. This system was applied to both thalassemia and control samples to identify erythrocytes. The eXtreme Gradient Boosting (XGB) and logistic regression (LR) models were developed to distinguish thalassemia cases from controls, classify thalassemia subtypes, and differentiate thalassemia from iron deficiency anemia (IDA) based on the morphological features of red blood cell (RBC) identified by the system. Results: The XGB and LR models achieved AUROC values of 0.92 and 0.98, respectively, for distinguishing thalassemia cases from controls. Subclass analysis showed that the XGB model reached an AUROC of 0.99 for α-thalassemia and 0.98 for β-thalassemia, while the LR model achieved an AUROC of 0.95 for α-thalassemia and 0.99 for β-thalassemia. The LR model outperformed the XGB model (AUROC 0.88 vs. 0.75) in differentiating IDA from thalassemia. Conclusions: Both the XGB and LR models demonstrate high accuracy in predicting thalassemia and distinguishing its subtypes, based on using RBC morphological features extracted by an AI-driven detection system.

Acute myeloid leukemia (AML), especially therapy-related (t-AML) or secondary AML (s-AML), presents complex therapeutic challenges. CPX-351, a liposomal formulation of cytarabine and daunorubicin, has demonstrated superior outcomes compared to standard 7 + 3 chemotherapy. However, optimal post-remission strategies are debated. This retrospective study evaluates the feasibility and efficacy of intermediate-dose ARA-C (IDAC), total dose of 8–9 g/m², following CPX-351 in 47 patients from three Italian centers. Median patient age was 69, with 64% having AML with myelodysplasia-related changes (MRC-AML). Based on the 2017 European LeukemiaNet (ELN) risk stratification, 8 patients were classified as favorable, 20 as intermediate, and 19 as adverse. The median overall survival (OS) was 21 months (IC95% 17–43), with 85% alive at 12 months and 48.4% at 24 months. Event-free survival (EFS) was 14.9 months (IC95% 11.7–28.2). Multivariate analyses identified adverse-risk ELN-2017 and MRD-positivity after CPX-351 as negative predictors for OS. IDAC was well tolerated, with manageable toxicities: neutropenic fever (27, grade 1–3) and mucositis (4, grade 2–3). Importantly, 70% of patients achieved stable or improved measurable residual disease (MRD) after consolidation. The study underscores IDAC as a viable consolidation strategy, especially for patients unable to receive further CPX-351 or awaiting transplant. Despite its retrospective nature and limited sample size, the findings suggest that IDAC may offer improved outcomes, including lower costs, compared to CPX-351.

Prognosis of adult patients with relapsed/refractory (r/r) or measurable residual disease (MRD)–positive B-precursor acute lymphoblastic leukemia (B-ALL) remains poor. Blinatumomab induces complete remissions (CR) and MRD negativity in a subset of patients, yet overall survival remains limited. As BCL2 overexpression contributes to leukemic cell survival and therapy resistance, combining Blinatumomab with the BCL2 inhibitor Venetoclax may enhance therapeutic efficacy. The GMALL-BLIVEN (NCT05182385) phase I multicenter trial evaluated the safety and feasibility of Venetoclax plus Blinatumomab in adults with CD19⁺, Philadelphia chromosome–negative r/r or MRD-positive B-ALL. Dose escalation followed a 3 + 3 design across three Venetoclax dose levels (DL-1: 400 mg; DL-2: 600 mg; DL-3: 800 mg) administered from day − 7 to day 42, with Blinatumomab given per label. The primary endpoint was determination of the maximum tolerated dose (MTD); key secondary endpoint was achievement of molecular complete remission (MOL-CR) by centralized IG/TR MRD assessment (sensitivity ≥ 10⁻⁴). Nine patients (median age 52 years, range 22–71) were enrolled across four German centers: four with r/r B-ALL and five with MRD-positive disease. Molecular subtypes included ZNF384-rearranged (n = 2), BCR::ABL1-like (n = 2), CEBP-rearranged (n = 1), hypodiploidy (n = 1), B-ALL NOS (n = 2), and KMT2A-rearranged (n = 1). No dose-limiting toxicities were observed, and the MTD was not reached. Treatment-emergent grade ≥ III toxicities included neutropenia, febrile neutropenia, cytokine release syndrome, and ICANS; no 30- or 60-day mortality occurred. Six patients completed two full cycles without treatment interruptions. The recommended phase II dose (RP2D) was established as Venetoclax 800 mg daily plus standard-dose Blinatumomab. All nine patients were evaluable for response. Among r/r B-ALL, responses included PR (n = 1), CR (n = 1), and PD (n = 2). Among MRD-positive patients, 4/5 achieved MOL-CR. Four patients were successfully bridged to allogeneic stem cell transplantation. After a median follow-up of 17.8 months, median overall survival was 15.0 months (r/r: 6.6 months; MRD-positive: 16.9 months). Non-responders were enriched for adverse molecular subtypes (BCR::ABL1-like and hypodiploid B-ALL). Venetoclax combined with Blinatumomab is safe and feasible in adults with r/r or MRD-positive B-ALL, without increased rates of CRS or neurotoxicity compared with Blinatumomab alone. High rates of MRD clearance were observed in MRD-positive patients. The phase II portion of GMALL-BLIVEN is ongoing at the RP2D of Venetoclax 800 mg daily.

Clonal heterogeneity within chronic lymphocytic leukemia (CLL) has been increasingly recognized as a factor that may influence disease progression, treatment response, and prognosis. Here, we report a rare case of CLL with two distinct B-cell populations displaying distinct immunophenotypic characteristics, genetic mutations, and genetic evolution. The two aberrant mature B cell populations were identified in peripheral blood (PB) and bone marrow (BM) through multiparametric flow cytometry (MFC) with identical light chain restriction but distinct immunophenotypes. The first population (CD5 + CD23+CD200+) was consistent with typical CLL, while the second (CD5-CD23-CD200-) displayed atypical features. Further characterization through flow sorting, fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS) revealed that both populations shared the same BCL2-IgH translocation and an identical IGHV gene usage, but exhibited different IGHV mutation rates. NGS revealed that a common progenitor cell with BCL2-IgH translocation and mutations in TP53, KMT2A, KMT2C, and KMT2D gave rise to two distinct subclones: one (CD5 + CD23+CD200+) CLL driven by mutations in TNFAIP3 and BCORL1, and the other (CD5-CD23-CD200-) driven by mutations in EP300, NOTCH1, and BCL2. This case highlights the significance of clonal heterogeneity in CLL and underscores the crucial role of MFC, flow sorting, and molecular genetics in diagnosing and understanding the complex evolution of this disease.

Acute myeloid leukemia (AML) is a hematological malignancy characterized by clonal expansion of myeloid progenitors in the bone marrow, resulting in impaired hematopoiesis. AML remains challenging due to frequent disease recurrence and limited treatment alternatives, highlighting the necessity for further research. Corilagin, an ellagitannin isolated from ethnopharmacological plants, displays potential anti-cancer activity, but its anti-leukemic effects and mechanism in AML are unclear. This study aimed to assess whether corilagin induces cell death in AML cells, a cell-derived xenograft (CDX) model, and primary AML cells, and to elucidate its therapeutic mechanism in AML. Cell viability was measured using the Cell Counting Kit-8 and proliferation was assessed with an EdU imaging kit. Flow cytometry analyzed PI-positive cells. Pyroptosis was evaluated by morphology and LDH release. mRNA and protein levels were measured by qPCR and western blot. Stable cell lines with gene knockouts were created using CRISPR-Cas9. The therapeutic efficacy of corilagin was also tested in CDX models. Corilagin treatment induced pyroptotic bubbles in AML cells, increasing LDH release and PI-positive cells. Corilagin activated caspase-3, which cleaved gasdermin E (GSDME) to form active GSDME-NT, promoting pyroptosis. Corilagin also activated thioredoxin-interacting protein (TXNIP), and TXNIP knockdown by siRNA rescued corilagin-induced pyroptosis. Corilagin reduced viability and promoted pyroptosis in primary AML cells. In an AML CDX mouse model, corilagin inhibited leukemia progression and prolonged survival. Our results suggested that corilagin induced pyroptosis in AML by activating the TXNIP/caspase-3/GSDME pathway, offering a potential therapeutic strategy for AML.

Although Chimeric antigen receptor (CAR) T-cell therapy has achieved a high response rate in recurrent/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL), the prognosis of the patients who do not respond to this therapy or have a disease progression again is poor. A 69-year-old male patient was diagnosed with refractory follicular lymphoma (FL) had 43.6% abnormal B lymphocytes expressing CD20-, CD19+, CD22 + in his pleural effusion. He received anti-CD19 CAR T-cell combined with anti-CD22 CAR T-cell therapy in our hospital, but he achieved stable disease (SD) only two months after CAR-T cell infusion. When his disease progressed again, there were 40.2% abnormal B lymphocytes expressing CD19-, CD20-, CD22 + in pleural effusion. Because CD22 was the only antigen expressed on his lymphoma cells at this time, reduced-dose of Inotuzumab Ozogamicin (InO) was chosen as a salvage therapy (InO 1 mg on day 1, 8, 15). The main adverse events (AE) of this salvage therapy were haematological toxicity. He was evaluated as complete remission (CR) two months after InO salvage therapy. His haematological toxicity was gradually recovered in the following six months. To date, this refractory FL patient has achieved continuous CR and maintained more than three years of event-free survival from the salvage therapy of InO. InO might be an effective and feasible salvage therapy for refractory FL patients who have failed to CAR-T cell therapy. Moreover, immunotherapy of R/R B-cell NHL could be achieved through target selection of lymphoma cells.

Epiregulin, a polypeptide involved in inflammation, cell proliferation, tumor development, and tissue remodeling pathophysiology, plays a crucial role in the etiopathogenesis of malignancies. This prospective case-control study aimed to investigate the association between epiregulin levels and various clinical and laboratory parameters in HL patients to better understand its role in the disease. This study compared newly diagnosed 56 HL patients with 56 healthy controls to assess epiregulin levels in relation to factors such as cell type, staging, extranodal involvement, β2-microglobulin, lactate dehydrogenase (LDH), and C-reactive protein (CRP). Epiregulin levels were significantly elevated in HL patients (265.0 ± 36.0 pg/ml) compared to healthy controls (130.7 ± 21.8 pg/ml). While no significant differences were observed in epiregulin levels among different HL subtypes, higher levels were found in advanced stages (281.1 ± 32.2 pg/ml) compared to early stages (246.4 ± 31.3 pg/ml). Patients with splenic and extranodal involvement exhibited elevated epiregulin levels. Furthermore, a positive correlation was noted between epiregulin levels and CRP, LDH, and β2-microglobulin levels in HL patients. Epiregulin levels are elevated in patients with Hodgkin lymphoma and are associated with advanced disease stage, extranodal and splenic involvement, the presence of B symptoms, and key laboratory parameters. These findings suggest that epiregulin may be related to disease burden and activity in HL. Further prospective studies are warranted to clarify its clinical relevance.

To evaluate the prognostic value of TP53 mutations in patients with diffuse large B-cell lymphoma (DLBCL). We retrospectively analyzed the clinical data and gene sequencing results of 253 newly diagnosed DLBCL. Survival and correlation analyses were performed. We further revealed significant prognostic heterogeneity among different TP53 hotspot mutations, with mutations at codons G245, R175, R273, and R282 indicating a poorer prognosis. Within the DBD, mutations in exons 5, 7, and 8 were associated with poorer PFS, while mutations in exons 5, 6, and 8 were linked to poorer OS. Additionally, mutations in the Loop-L2, Loop-L3, and LSH motifs within the DBD were all significantly associated with unfavorable PFS and OS. Notably, in the cohort treated with R-CHOP plus novel agents (R-CHOP + X), there were no significant differences in response rates or survival between TP53-mutated and TP53 wild-type patients, suggesting this combination may overcome the adverse prognosis associated with TP53 mutations.TP53 mutation is a crucial adverse prognostic factor in DLBCL. Given the significant prognostic heterogeneity among different TP53 hotspot mutations, a more refined risk stratification based on the TP53 mutational profile is warranted in clinical practice. For patients with high-risk mutations, combining R-CHOP with targeted therapies and exploring novel combination strategies targeting specific pathways are recommended. In contrast, standard R-CHOP may remain an appropriate option for patients with low-risk mutations. Future prospective trials are needed to validate the efficacy of R-CHOP combined with targeted agents in TP53-mutated DLBCL to optimize treatment strategies and improve patient outcomes.