To evaluate the real-world efficacy and safety of iptacopan in complement inhibitor-naïve patients with paroxysmal nocturnal hemoglobinuria (PNH) in China. This retrospective study included data collected from patients who commenced iptacopan treatment for PNH. Changes in clinical and laboratory indicators were examined after 1, 3, and 6 months and during the subsequent follow-up. A total of 54 patients were enrolled, including 17 (31.5
Acute promyelocytic leukemia (APL) is curable with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), but differentiation syndrome (DS) remains a potentially life-threatening complication, with poorly understood pathogenesis. We investigated clinical, molecular and functional determinants of DS in APL. Two independent cohorts of APL patients were analyzed, including a real-life series (n = 34) and a cohort from the APL0406 trial (n = 18). Baseline and sequential RNA sequencing, and cytokine profiling were performed on PB samples. In vitro assays on human pulmonary microvascular endothelial cells were also performed (HPMECs). DS occurred in 47
Leukocyte Associated lmmunoglobulin Like Receptor 1 (LAIR1) has been found to be associated with chronic lymphocytic leukemia (CLL). Thus, we aimed to investigate the function of LAIR1 in cell cycle and apoptosis of CLL. Single-cell analysis was initially conducted to explore cellular signatures in CLL, and identified key cells to investigate LAIR1 expression in different cell types. The expression of LAIR1 was further analyzed between CLL and control samples in public datasets and human CLL cell line. According to the optimal cutoff value of LAIR1 expression, CLL samples were categorized into two expression groups, and survival outcomes was compared by Kaplan-Meier analysis. Subsequently, LAIR1 overexpression CLL cell lines were constructed, and validated by real time-quantitative polymerase chain reaction (RT-qPCR) and Western blot. Moreover, flow cytometry assays were performed to investigate the impact of LAIR1 on the CLL cell cycle and apoptosis. Macrophages were identified as key cells in the CLL microenvironment, exhibiting the highest expression of LAIR1. LAIR1 expression was significantly decreased in CLL group for both bioinformatics and experimental analyses, and low LAIR1 expression group had the worse prognosis. RT-qPCR and Western blot analyses confirmed that LAIR1 expression was significantly increased in CLL cell line with LAIR1 overexpression. Finally, flow cytometry analysis indicated that CLL cell with LAIR1 overexpression had shortened S-phase length and increased apoptotic rates. This study found overexpression of LAIR1 reduced S-phase length and increased apoptotic rates of CLL cells, offering novel reference for the effect of LAIR1 in CLL.
The phase III BRUIN CLL-313 and CLL-314 trials have established pirtobrutinib, a noncovalent Bruton tyrosine kinase (BTK) inhibitor, as a candidate for first-line therapy in chronic lymphocytic leukemia (CLL), and all-lines regulatory approval has now been granted in the European Union. We highlight an untested asymmetry: after failure of covalent BTK inhibitors, pirtobrutinib retains phase III–validated activity, whereas resistance to first-line pirtobrutinib can arise through kinase-domain mutations (e.g., A428D, L528W) that confer in vitro cross-resistance to covalent agents, the class that currently anchors relapse management. No clinical data exist on covalent BTK inhibitors after pirtobrutinib failure. We argue that, until reverse-sequence data emerge, a cautious approach that retains the clinically validated covalent-first sequence is reasonable for patients expected to need multiple lines of therapy, and we suggest mutation testing at progression, registry tracking of post-pirtobrutinib outcomes, and explicit discussion of sequencing in forthcoming guideline updates.
Treatment response, survival outcomes, and factors related to venetoclax (VEN)-based therapy were assessed in patients with acute myeloid leukemia (AML), including newly diagnosed AML (ND-AML) and relapsed/refractory AML (R/R AML). We also developed a model to predict composite complete remission (CRc) after the first treatment cycle. This retrospective study included 216 patients with AML who received VEN-based regimens at the First Hospital of Lanzhou University between March 2020 and May 2025. Treatment response, overall survival (OS), and factors related to CRc and OS were evaluated. A multivariable model for CRc was developed and internally validated using 1,000 bootstrap resamples. Of the 216 patients, 165 had ND-AML and 51 had R/R AML. CRc was achieved in 74.5
Patients with malignant lymphomas are at increased risk for severe COVID-19. In the general population, outcomes of COVID-19 have improved dramatically over time due to increasing immunity through vaccination or infection and due to improved clinical care. It is unclear whether outcomes of COVID-19 in patients with lymphoma have improved similarly over time. We performed a multi-center retrospective study of lymphoma patients with COVID-19 at five tertiary care centers of the Bavarian Cancer Research Center (BZKF) in Germany, evaluating baseline characteristics as well as COVID-19 management and outcomes across different pandemic waves from March 2020 to March 2022. Clinical management of COVID-19 as well as vaccination rates changed significantly over time. In the most recent pandemic wave (cases after December 27th 2021), 88
Bronchiolitis Obliterans Syndrome (BOS) after pediatric allogeneic hematopoietic stem cell transplantation (allo-HSCT) carries high mortality, partly due to diagnostic delays and static assessments. This brief report evaluates a dynamic monitoring strategy for early warning. This single-center, retrospective cohort study included 201 children who underwent allo-HSCT between January 2015 and December 2024, comprising 29 patients with BOS and 172 non-BOS controls.Independent risk factors for BOS were identified using multivariate Cox regression analysis. Diagnostic performance of a relative FEV1 decline ≥ 10
Risk stratification in myelofibrosis (MF) is increasingly shaped by molecularly informed tools. MIPSS70 and MYSEC‑mPM/MYSEC‑kmPM have reclassified a substantial proportion of patients previously considered lower risk by clinical scores. Whether early‑treatment dynamic models retain prognostic value within molecularly annotated cohorts remains unknown. We evaluated RR6 and iRR6 in 197 MF patients classified as intermediate‑1 risk by MIPSS70 (92 PMF) or MYSEC‑mPM/kmPM (105 SMF; 85 evaluable for kmPM). High‑molecular‑risk variants were detected in 56.5
Follicular lymphoma (FL) is an incurable, indolent non-Hodgkin lymphoma with a high relapse rate despite effective chemoimmunotherapy. Lenalidomide, an immunomodulatory agent, in combination with rituximab (R²), has been evaluated as an alternative to chemoimmunotherapy and to other standard regimens in FL. We conducted a systematic review and meta-analysis to assess the efficacy and safety of R² compared with standard regimens in FL. A PRISMA-guided search of PubMed, Embase, and Cochrane Library through May 2025 identified randomized controlled trials (RCTs) comparing R² to rituximab monotherapy, chemoimmunotherapy, or lenalidomide alone. Four RCTs (n = 1315 patients) were included. Primary endpoints were overall response rate (ORR), complete response (CR) and partial response (PR). Secondary outcomes were 2-year progression-free survival (PFS), 3-year overall survival (OS) and adverse events. R² did not differ significantly from comparators in 2-year PFS in the primary analysis (RR = 1.53, 95
Waldenstrom’s macroglobulinemia (WM) is characterized by familial aggregation. The study displayed the characteristics and outcomes of patients with WM in siblings. Ten cases (five pairs) were recognized as WM in siblings. The earliest pair (cases 3 and 4) was identified in 2002 and 2005, respectively, while the recent pair (cases 7 and 8) was confirmed in 2022. Males accounted for 90
Hodgkin lymphoma (HL) is a rare haematological malignancy that arises from clonal B lymphocytes. Among people living with human immunodeficiency virus (HIV), it is the most common non-acquired immunodeficiency syndrome (AIDS)-defining cancer, with classical Hodgkin lymphoma (CHL) representing the predominant subtype. It is a lymphoid disease, typically involving the axial body lymph nodes, and rarely involving true extranodal sites outside the bone marrow, liver, and spleen. Here we report a rare case of a 41-year-old female, HIV-positive, who presented to multiple healthcare facilities in KwaZulu Natal (KZN), South Africa (SA), treated unsuccessfully for recurrent sexually transmitted infections (STI). Clinical exam revealed a macroscopic cervical mass with the primary suspicion of cervical cancer. Biopsy of the lesion revealed ectocervix with an invasive tumour comprising of mononuclear variant and classic Reed-Sternberg cells, and special stains demonstrated CD15, CD30 and Epstein–Barr virus-encoded small RNA (EBER) immunopositivity, in keeping with CHL.
Hypomethylating agents (HMA) plus venetoclax (VEN) is a standard frontline therapy for unfit, newly diagnosed acute myeloid leukemia (AML), but prolonged cytopenia and infections often limit treatment continuity. We performed a retrospective, two-stage cohort study (Jan 2021–Jun 2025) evaluating whether early bone marrow assessment-guided, response-adapted VEN management improves tolerability without compromising efficacy. Stage 1 compared patients undergoing early bone marrow assessment (cycle 1, days 14–21) with subsequent bone marrow-guided VEN adaptation versus a conventionally managed cohort. Stage 2 was a landmark analysis at cycle 3 day 1 (C3D1) comparing VEN shortening (≤ 14 days/cycle) versus continuation (> 14 days/cycle) in responding patients. Among 371 evaluable patients, 200 underwent early bone marrow-guided management, yielding lower day-56 infection-related hospitalization (24.0
The combination of hypomethylating agents and venetoclax (VEN) has emerged as a new standard of care for elderly or unfit patients. In this study, we conducted a retrospective analysis of 37 patients with acute myeloid leukemia (AML) to investigate the efficacy and safety of a low‑dose 10‑day decitabine (DEC) combined with venetoclax (VEN) regimen (DEC 6 mg/m2 for 10 days and VEN for 14 days). The composite complete remission (CRc) rate was 78.4
Fludarabine is widely used in conditioning regimens for allogeneic hematopoietic stem cell transplantation (allo-HSCT). While myelosuppression is a well-recognized adverse effect of fludarabine, fludarabine-associated central nervous system toxicity is rare but potentially fatal and may be under-recognized in clinical practice. Herein, we report three cases of severe neurological impairment after allo-HSCT with fludarabine-based conditioning. All the patients had multiple risk factors including extensive prior cytotoxic therapy and renal dysfunction. Neurological symptoms were characterized by progressive impairment of consciousness, and two patients developed visual disturbances. Brain magnetic resonance imaging revealed bilateral, symmetric white matter lesions involving the periventricular white matter and optic radiation with restricted diffusion. Cerebrospinal fluid analysis revealed elevated protein levels in all the patients, with increased myelin basic protein levels in two of the patients, suggesting active demyelination. All the patients developed progressive renal dysfunction after fludarabine administration, which required dialysis, suggesting that dynamic changes in renal function may contribute to increased drug exposure and neurotoxicity. Although limited by the small number of cases, our findings highlight the importance of recognizing fludarabine-associated neurotoxicity as a differential diagnosis of neurological complications after allo-HSCT, particularly in high-risk patients.
Adoptive cellular immunotherapy has transformed the treatment landscape for hematologic malignancies; however, its broader application to solid tumors remains limited by antigen heterogeneity, inadequate persistence, restricted tumor infiltration, and the profoundly immunosuppressive tumor microenvironment (TME). While conventional CAR-T cell therapy has demonstrated remarkable clinical success, no single immune-cell platform is likely to overcome all biological barriers encountered in complex solid tumors. Emerging evidence instead supports a shift toward an integrated cellular immunotherapy ecosystem that combines the complementary strengths of multiple engineered immune cell populations. In this review, we present a unifying framework for the multi-layered engineering of next-generation immune cell therapies, encompassing CAR-natural killer (CAR-NK) cells, TCR-engineered αβ T cells, γδ T cells, CAR-natural killer T (CAR-NKT) cells, and CAR-macrophages. Rather than considering these platforms as isolated technologies, we examine how shared engineering strategies, including cytokine armoring, CRISPR-based genome editing, protein-level receptor optimization, tumor-responsive gene circuits, metabolic reprogramming, and induced pluripotent stem cell (iPSC)-based manufacturing, can be integrated to enhance persistence, functionality, safety, and resistance to TME-mediated suppression. We further discuss the biological rationale, preclinical advances, and emerging clinical evidence supporting each platform, highlighting their distinct and complementary mechanisms of tumor recognition and immune activation. Finally, we propose that the future of cancer immunotherapy lies not in the optimization of a single cellular modality, but in the development of synergistic, scalable, and off-the-shelf engineered immune-cell networks capable of delivering durable and effective responses against heterogeneous solid tumors.
To explore the key influencing factors of the risk of nosocomial infection in patients with multiple myeloma (MM), to construct a prediction model to effectively assess the risk of infection, and to provide a basis for individualized infection prevention and control. 245 patients with MM admitted to the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine from 2005 to 2024 were retrospectively included, and the patients’ gender, age, BMPC
We reviewed the emerging clinical and biological evidence that supports the broader interpretation of arterial thrombosis as a biological turning point that identifies patients who are entering a more aggressive phase of classic myeloproliferative neoplasms. Findings from multistate analyses, international registry studies, nested case-control investigations, and recent translational research were integrated. We showed that arterial thrombosis is associated not only with recurrent vascular events but also with increased mortality, progression to myelofibrosis and blast phase, and, in selected patient populations, the subsequent development of solid cancers. We discuss the biological mechanisms that may underlie these associations, including persistent JAK2-driven inflammation, endothelial dysfunction, platelet-leukocyte interactions, neutrophil extracellular trap formation, immune remodelling, and clonal evolution. Particular attention is given to emerging biomarkers, such as JAK2V617F variant allele frequency and the neutrophil-to-lymphocyte ratio, which provide complementary information on clonal burden and inflammatory activity and may improve biological risk stratification. Finally, we discuss the clinical implications of this evolving paradigm, proposing that patients experiencing arterial thrombosis should undergo closer surveillance and be considered for biology-directed therapeutic strategies aimed at suppressing both clonal expansion and chronic thrombo-inflammation, rather than receiving secondary vascular prevention alone.
Patients with newly diagnosed acute leukemia are at increased risk of bleeding during vascular access because of thrombocytopenia and coagulopathy. The primary objective of this single-center retrospective study (November 2023–August 2024; Ruijin Hospital) was to evaluate the feasibility and safety of a peripherally inserted central catheter (PICC) puncture and nursing protocol incorporating ultrasound-guided Seldinger puncture, controlled sheath withdrawal with gauze-assisted compression, and localized hemostatic dressing in 101 patients prior to chemotherapy. The first-attempt success rate was 95.1
Women with essential thrombocythemia (ET) and polycythemia vera (PV) are at increased risk of pregnancy complications. During pregnancy, hematologic parameters tend to approach normal values, and previous studies have reported that a greater decline in platelet counts in ET is associated with reduced risk of complications. In this study, we examined longitudinal trajectories of platelet count, hemoglobin, hematocrit, and leukocyte count during pregnancy, characterized pregnancy outcomes, and investigated the association between platelet trajectories and preeclampsia. We established a longitudinal cohort of pregnant women with ET and PV in the Capital Region and Region Zealand between 2010 and 2024, using data from regional laboratory information systems and Danish health registries. In total, 41 ET and 5 PV pregnancies in 35 women were included. The mean age at MPN diagnosis was 30.1 years in women with ET and 34.1 years in women with PV. In ET pregnancies, platelet counts, hemoglobin, hematocrit and leukocyte count changed by − 44
Acute myeloid leukemia (AML) is a genetically heterogeneous hematologic malignancy in children, with molecular alterations playing critical roles in disease development and therapeutic responses. The CBFA2T3::GLIS2 (C/G) is the most frequent genetic alteration identified in non-Down syndrome acute megakaryoblastic leukemia (AMKL) and results from a cryptic inversion involving the subtelomeric region of chromosome 16. Multiple chimeric transcripts can be generated depending on the breakpoint location, with CBFA2T3-ex11/GLIS2-ex3 being the predominant transcript. This fusion gene is associated with chemotherapy resistance and an unfavorable clinical outcome. Although initially identified in AMKL, it has also been detected in several cytogenetically normal AML subtypes, including M0, M1, M2, M4, and M5. However, the molecular mechanisms underlying C/G fusion-driven leukemogenesis remain incompletely characterized. This review provides an overview of the pathogenic mechanisms, emerging therapeutic strategies, and clinical challenges associated with C/G-positive pediatric AML.
