Objective: To explore the variables associated with severe cytopenia in patients with chronic phase chronic myeloid leukemia (CML-CP) receiving initial tyrosine kinase inhibitor (TKI) therapy. Methods: Data from consecutive patients aged ≥18 years with CML-CP who received imatinib, nilotinib, or flumatinib at Peking University People's Hospital between November 2006 and January 2025 were retrospectively reviewed. Binary logistic regression models were applied to analyze the variables associated with severe cytopenia (according to Common Terminology Criteria for Adverse Events version 5.0, with a focus on grade 3/4 leukocytopenia or thrombocytopenia) . Results: This study included 1 906 patients initially receiving imatinib (n=1 542, 80.9%), nilotinib (n=256, 13.4%), and flumatinib (n=108, 5.7%). The median age was 41 (range, 18-83) years, and 1 141 (59.9%) patients were male. At a median of 1 (range, 0.2-3) month, 186 (9.8%) patients developed grade 3/4 cytopenia, primarily thrombocytopenia, and persisted for 0.6 (range, 0.1-10.6) months, including 68 (3.6%) patients who developed grade 4 cytopenia. No significant difference in the incidence of grade 3/4 cytopenia was observed among patients receiving the three TKIs, whereas grade 4 cytopenia was more common in those receiving the second-generation (2G) TKI (nilotinib and flumatinib) compared with imatinib (7.3% vs 2.7%, P=0.001). Multivariate analysis revealed that female sex, decreased hemoglobin level, and increased white blood cell count (or splenomegaly) were significantly associated with the higher incidence of severe cytopenia in patients receiving TKI. Based on the adverse variables, patients receiving imatinib were categorized into low- and high-risk groups, and those receiving 2G-TKI were classified into low-, medium-, and high-risk groups with a significant difference in the incidence of grades 3/4 and 4 cytopenia (P<0.001) . Conclusion: Severe cytopenia is a common adverse event in patients with CML-CP receiving TKI therapy. Grade 4 cytopenia is more common in those receiving 2G-TKI compared with imatinib. High-risk factors for severe cytopenia associated with TKIs included female sex, decreased hemoglobin level, increased white blood cell count, and splenomegaly at initial diagnosis. Close monitoring is necessary during the early phase of TKI-therapy for the high-risk group.

Objective: To explore the clinical characteristics, treatment patterns, and outcomes of patients with autoimmune hemolytic anemia (AIHA) in a single-center retrospective cohort. Methods: Clinical data of 125 patients with AIHA admitted to the Blood Diseases Hospital, Chinese Academy of Medical Sciences, between July 2019 and February 2025, were retrospectively analyzed to investigate their clinical characteristics, treatment patterns, and outcomes. Results: Glucocorticoid monotherapy was the most commonly administered first-line treatment, whereas 78.2% of the patients received glucocorticoids in combination with rituximab during the disease course. The overall response rate (ORR) and the sustained remission rate were 61.3% and 10.7% in 75 patients receiving glucocorticoid monotherapy as first-line treatment and 88.0% and 60.0% in 25 patients treated with glucocorticoids plus rituximab, respectively. The median number of treatment lines was two, with approximately one-third of the patients requiring three or more lines of therapy. In the context of clinical research, 27 (21.6%) patients with relapsed/refractory disease received exploratory treatment with novel targeted agents, with a significantly higher median number of treatment lines compared with those who did not [4 (2-12) vs 2 (1-6), P<0.001]. After treatment, 44.4% of patients achieved remission, whereas 40.7% of patients had their HGB levels normalized. Regarding complications, venous thromboembolism occurred in 8 patients (6.4%). Further, 36 patients (28.8%) developed infections, with a significantly higher number of treatment lines in the infection group than in the noninfection group (P<0.001) . Conclusion: The therapeutic approaches for AIHA demonstrate remarkable heterogeneity. Glucocorticoid monotherapy remains the most commonly administered first-line treatment; however, its ability to maintain sustained remission is limited. Glucocorticoid treatment in combination with rituximab demonstrated a higher ORR and sustained remission rate. Patients who developed infections during the disease course required significantly more lines of therapy, emphasizing the importance of infection prevention and surveillance in clinical practice.

This report describes a case of Niemann-Pick disease caused by double missense mutations in the SMPD1 gene and investigates the morphological relationship between Niemann-Pick cells and sea-blue histiocytes. The patient's bone marrow smear showed typical Niemann-Pick cells, containing small to moderate sea-blue granules, as well as sea-blue histiocytes. Next-generation sequencing revealed heterozygous SMPD1 mutations c.1361C>A (p. Ala454Asp) and c.1666C>T (p. His556Tyr). While these mutations were previously reported in the literature, their clinical significance remains unclear. Since missense mutations in SMPD1 are pathogenic and can cause Niemann-Pick disease, it is hypothesized that a morphological link exists between Niemann-Pick cells and sea-blue histiocytes. Combining bone marrow morphology with genetic testing can improve the diagnostic accuracy for this disease and other related lipid storage disorders.

This study retrospectively analyzed the clinical data of 15 patients diagnosed with large granular lymphocytic leukemia (LGLL) at the First Affiliated Hospital of Chongqing Medical University between January 2017 and December 2024. The median age was 50 years, and the main clinical manifestations included fatigue (73.3%), splenomegaly (46.7%), and lymphadenopathy (33.3%). None of the patients had autoimmune diseases. Laboratory examinations primarily demonstrated decreased hemoglobin levels (100%) and/or neutropenia (73.3%). The bone marrow smears showed an increase in lymphocyte proportion, and pure red cell aplasia was frequently observed. The typical immunophenotype was TCRαβ(+)TCRγδ(-)CD3(+)CD4(-)CD8(+)CD16(-)CD10(-)CD30(-)CD45RA(+)CD45RO(-)CD56(-)CD25(-), with monoclonal T-cell proliferation confirmed in all patients. Further, 8 patients demonstrated decreased complement C3 or C4 levels. The overall response rate of first-line immunosuppressive therapy for patients with LGLL was 85.7% (12/14) .

The clinical course and management of a patient with refractory immune thrombotic thrombocytopenic purpura (iTTP) admitted to the Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, were retrospectively analyzed, alongside a review of pertinent literature. Upon admission, the patient had a PLASMIC score of 6, and emergency therapeutic plasma exchange (TPE) combined with glucocorticoid therapy was immediately initiated. Further examinations revealed an ADAMTS13 activity of 2.9% and a positive inhibitor, thereby confirming iTTP diagnosis. After 5 consecutive days of TPE and glucocorticoid treatment, the patient demonstrated no clinical response, consistent with a diagnosis of refractory iTTP. Rituximab was subsequently added; however, the platelet count continued to decrease, and the disease progressed. After adding caplacizumab to the original regimen, the platelet and lactate dehydrogenase levels rapidly normalized, ADAMTS13 activity recovered to 24.9%, and no serious adverse events occurred during the treatment. This case indicates that incorporating caplacizumab into the combination therapy strategy for patients with refractory iTTP who failed conventional therapies effectively achieves rapid disease control.

Objective: To compare the efficacy and safety of venetoclax (VEN) combined with azacitidine (AZA) (VA) versus decitabine combined with cytarabine+aclarubicin+granulocyte colony-stimulating factor (CAG) (D-CAG) regimen in the treatment of elderly patients with relapsed or refractory acute myeloid leukemia (RR-AML) . Methods: This prospective randomized study was conducted using VA and D-CAG regimens for the salvage treatment of elderly patients with RR-AML. A sealed envelope was used for randomization, with a planned enrollment of 50 patients. The primary endpoints were objective response rate (ORR) and composite complete remission (cCR) rate, whereas the secondary endpoints included overall survival (OS), duration of remission (DOR), and safety. Results: From January 2021 to June 2024, 50 elderly patients with RR-AML received at least one cycle of either VA or D-CAG treatment and completed efficacy and safety assessments. The VA group comprised 22 patients with a median age of 63.0 (range: 60.8-69.3) years, and the D-CAG group included 28 patients with a median age of 66.5 (range: 62.3-69.0) years. DNA methylation gene mutations were the most frequent, comprising 8 cases (36.4%) in the VA group and 9 cases (32.1%) in the D-CAG group. The ORR was 68.2% (15/22) and 53.6% (15/28) and the cCR rate was 68.2% (15/22) and 46.4% (13/28) in the VA and D-CAG groups, respectively. No significant difference in ORR or cCR was observed between the two groups. Subgroup analysis revealed that the cCR rate in the VA group with AML-MR gene mutations was 6/7, which was higher than 4/10 in the D-CAG group. Patients were categorized into early relapse, late relapse, and refractory groups. The cCR rate for early relapse was below 40% with both regimens. In the late relapse group, 4 of 5 patients in the VA group achieved cCR, and both patients in the D-CAG group achieved cCR. The median follow-up time was 19 months (IQR: 11-48.5 months). The median OS was 16 months in the whole cohort, with 19 months for the VA group and 11 months for the D-CAG group (P=0.189). Among the 30 patients who achieved cCR after salvage chemotherapy (VA=15 and D-CAG=15), the DOR in the VA group demonstrated a significant advantage over that in the D-CAG group (not reaching vs 6 months, P=0.023). The median OS for the early relapse, late relapse, and refractory groups was 5, 21, and 18 months, respectively, with significantly better efficacy observed in the late relapse group (P=0.020). Four patients who received salvage treatment followed by allogeneic stem cell transplantation had no evidence of disease, demonstrating a survival advantage compared with nontransplant patients (P=0.007). The incidence of rash (27.3% vs 3.6%, P=0.047) and diarrhea (40.9% vs 7.1%, P=0.012) in the VA group was significantly higher than that in the D-CAG group. Conclusion: The VA and D-CAG regimens have comparable efficacy for elderly patients with RR-AML. Patients with late relapse demonstrated better efficacy with both regimens compared with the early relapse and refractory groups.

Objective: To investigate the effect of transplant conditioning intensity (TCI) on transplant outcomes in patients with myelodysplastic neoplasms (MDS) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: This multicenter retrospective cohort study included 337 patients with MDS undergoing allo-HSCT between February 2019 and April 2025 in four transplant centers in China. Patients were categorized based on TCI scores into TCI-1 (1-2 points, low intensity), TCI-2 (2.5-3.5 points, moderate intensity), and TCI-3 (4-6 points, high intensity) groups. The Fine-Gray competing risk model was applied to analyze nonrelapse mortality (NRM) and relapse. Overall survival (OS) was estimated employing the Kaplan-Meier method and compared using the log-rank test. Inverse probability of treatment weighting (IPTW) was performed to balance covariates among groups to eliminate baseline confounding bias. Furthermore, a doubly robust (DR) model combined with the Fine-Gray competing risk model was applied to assess the independent effect of TCI on NRM. Results: Unweighted analysis revealed that the 3-year NRM post-transplantation in the TCI-1, TCI-2, and TCI-3 groups was 7.7% (95% CI: 0.4%-15.1%), 8.3% (95% CI: 4.3%-12.3%), and 27.1% (95% CI: 18.0%-36.3%), respectively (P=0.008). No significant difference in the risk of NRM was observed between the TCI-1 and TCI-2 groups (sHR=1.106, 95% CI: 0.371-3.298, P=0.857), whereas the risk of NRM in the TCI-3 group was significantly higher than that in the TCI-1 (sHR=4.023, 95% CI: 1.414-11.452, P=0.009) and TCI-2 groups (sHR=3.673, 95% CI: 1.951-6.912, P<0.001). The multivariable analysis identified TCI-3, age of ≥50 years, and hematopoietic cell transplantation-comorbidity index score of >2 points as independent risk factors for NRM. After IPTW adjustment, the results remained consistent: the risk of NRM in the TCI-3 group remained significantly higher than that in the TCI-1 (sHR=6.090) and TCI-2 groups (sHR=4.562). The comparison of the contribution of NRM to transplant failure across groups at different time points revealed a significantly increased contribution of NRM to transplant failure with increasing conditioning intensity, especially in the TCI-3 group (sHR=5.011, 95% CI: 1.118-22.452, P=0.035). NRM within 3 years posttransplantation accounted for 39.0% of transplant failures. The Kaplan-Meier curve revealed that the 3-year OS rate was the lowest in the TCI-3 group (61.2%, 95% CI: 51.5%-72.7%). No statistically significant difference in the 3-year cumulative incidence of relapse was observed across the three groups. Conclusion: High-intensity conditioning failed to translate into a reduction in relapse rate but rather significantly increased the risk of NRM and compromised OS after allo-HSCT. Low- and moderate-intensity conditioning achieves a better balance between controlling toxicity and maintaining efficacy.

Objective: This study aimed to analyze the disease burden and trends of Burkitt lymphoma (BL) in China between 1990 and 2021. Methods: Based on the 2021 Global Burden of Disease Study data, stratified by age, sex, and region, the disease burden was analyzed by BL incidence, mortality, and disability-adjusted life year (DALY). Regression analysis was conducted with joinpoint software to calculate the average annual percentage change (AAPC) of age-standardized rates to analyze the changing trends and compare them with global data. Results: In 2021, a total of 1,322 new BL cases were reported in China, with an age-standardized incidence rate of 0.08/100,000. Of these patients, 241 died, with an age-standardized mortality rate of 0.01/100,000. DALY was 9,516 person-years, with an age-standardized DALY rate of 0.68/100,000. The disease burden of BL demonstrated significant differences across various age and sex groups. The highest BL disease burden was observed in the age group over 80 years old, with an incidence of 0.60/100,000, mortality of 0.11/100,000, and DALY rates of 1.59/100,000. BL disease burden was higher in males than in females, with age-standardized incidence rates of 0.11/100,000 and 0.05/100,000, age-standardized mortality rates of 0.02/100,000 and 0.01/100,000, and age-standardized DALY rates of 0.92/100,000 and 0.43/100,000, respectively. Significant regional differences were observed in BL disease burden. The highest-ranked age-standardized DALY rates were reported in Shanghai [1.78 (95% CI: 0.16-3.63) /100,000], Tibet Autonomous Region [1.15 (95% CI: 0.41-2.23) /100,000] and Qinghai Province[1.06 (95% CI: 0.49-1.87) /100,000], whereas the lowest-ranked were observed in Macao Special Administrative Region [0.32 (95% CI: 0.07-0.57) /100,000], Chongqing [0.36 (95% CI: 0.14-0.72) /100,000] and Ningxia Hui Autonomous Region [0.48 (95% CI: 0.25-0.92) /100,000]. From 1990 to 2021, the age-standardized incidence rate of BL increased by 187.12%, whereas the age-standardized mortality rate and age-standardized DALY rate decreased by 37.72% and 52.70%, respectively. The AAPCs were 3.49%, -1.46%, and -2.40%, respectively. Conclusions: The disease burden of BL in China has been alleviated to a certain extent; however, significant differences were observed among different ages, genders, and regions. Comprehensive prevention and control strategies should be formulated according to local conditions for different populations to further reduce the disease burden.

Platelets play a crucial role in atherosclerosis and thrombus formation, and their activation is regulated by reactive oxygen species (ROS). ROS in platelets primarily originates from nicotinamide adenine dinucleotide phosphate oxidase (NOX). Upon activation of glycoprotein Ⅵ (GPⅥ), ROS generation can be induced through both spleen tyrosine kinase (Syk) -dependent and Syk-independent pathways. In addition, the protease-activated receptor (PAR) signaling pathway not only activates NOX, but our latest research has revealed that it can also induce mitochondria-dependent ROS generation independently of GPⅥ. This finding expands the redox signaling pathways regulated by PAR and suggests mitochondria as a potential novel target for antithrombotic interventions. Endogenous ROS participate in the cascade of platelet activation and thrombus stabilization by modifying key signaling proteins and regulating ion channel function. Therefore, targeting ROS generation pathways associated with GPⅥ/PAR holds promise for developing precise therapeutic strategies for thrombotic diseases. This review summarizes the underlying mechanisms and provides a theoretical basis for the prevention and treatment of conditions such as atherosclerosis.