Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi最新文献

To improve the understanding of Löeffler endocarditis, we retrospectively analyzed six patients with eosinophilia, predominantly characterized by Löeffler endocarditis, who were treated at the First Affiliated Hospital of Soochow University from January 2019 to October 2024. Among the 6 patients, 5 were male, with a median age of 45.5 years (31-77 years). All patients demonstrated increased white blood cell count and eosinophil count in peripheral blood. Clinical symptoms and imaging examination were considered as Löeffler endocarditis, and two cases were complicated by cerebral infarction. Fusion gene testing was completed in five patients, with cases 4 and 5 demonstrating FIP1L1::PDGFRA fusion gene positivity, and case 6 with TLS::ERG (+) acute myeloid leukemia. Two patients with FIP1L1::PDGFRA positivity achieved rapid remission after imatinib treatment. Case 6 experienced symptom relief after glucocorticoids and hydroxyurea treatment, followed by complete remission after chemotherapy with the cytarabine (20 mg q12 h × 14 days), idarubicin (5 mg on days 2-12 every other day), and G-CSF (adjusted based on blood counts) regimen. After 8 months, the patient underwent allogeneic hematopoietic stem cell transplantation but died 1 year post-transplantation due to disease relapse complicated by infection. The remaining three patients demonstrated improvement after glucocorticoid treatment. Except for case 6, the other patients were still alive, with case 4 relapsing at 28 months after imatinib discontinuation and relieved after treatment re-initiation.

Objective: To identify factors influencing treatment-free remission (TFR) outcomes in children and adolescent patients with chronic myeloid leukemia (CML) after imatinib (IM) discontinuation. Methods: This multicenter retrospective study analyzed 36 children and adolescent patients with CML from eight hematology centers in China (December 1, 2016, to September 27, 2024) who discontinued IM therapy with documented post-cessation outcomes. Clinical characteristics and molecular response dynamics were assessed. Univariate analysis and multivariate Cox proportional hazards regression models were employed to assess factors associated with TFR outcomes. Results: A total of 36 patients were documented, comprising 17 males and 19 females. The median ages at CML diagnosis and IM discontinuation were 11 years (IQR: 5,16) and 20 years (IQR: 14,25), respectively. The median time from IM initiation to first deep molecular response (DMR) was 21 months (IQR: 13, 38). Pre-discontinuation, patients received IM for a median duration of 96 months (IQR: 84, 121) and maintained DMR for 74 months (IQR: 63, 89). With a median post-discontinuation follow-up of 38 months (IQR: 15, 68), cumulative TFR rates at 6, 12, 24, and 36 months were 74.1%, 60.7%, 60.7%, and 56.0%, respectively, generating an overall TFR rate of 58.3%. Fifteen patients lost major molecular response at a median of 5 months post-discontinuation (IQR: 3, 11). All 15 patients resumed tyrosine kinase inhibitor therapy, comprising 13 who restarted IM and 2 who switched to dasatinib. By the last follow-up, 13 (86.7% ) patients regained DMR after a median treatment duration of 5 months (IQR: 3, 17), and no disease progression occurred in any patient. Withdrawal syndrome occurred in 2 (5.6% ) patients. Univariate analysis revealed significantly higher TFR rates in patients with pre-discontinuation IM duration of ≥100 months vs <100 months (82.4% vs 36.8%, P=0.017) and pre-discontinuation DMR duration of ≥72 months vs <72 months (84.2% vs 29.4%, P=0.003). Multivariate Cox analysis identified pre-discontinuation DMR duration as an independent protective factor for TFR (HR=5.419, 95% CI: 1.524-19.272, P=0.009) . Conclusion: DMR duration was identified as an independent protective factor influencing TFR outcomes in children and adolescent patients with CML after IM discontinuation. Patients who maintained DMR for ≥72 months before IM discontinuation demonstrated a significantly higher TFR rate.

Objective: To investigate the clinical characteristics, treatment and prognostic factors in patients with primary central nervous system lymphoma (PCNSL) . Methods: This retrospective study included 52 patients with PCNSL treated in Peking University Third Hospital between January 2013 and December 2023. An analysis was conducted on the clinical characteristics, treatment and prognostic factors of the patients. Univariate and multivariate Cox proportional hazards models were used to determine factors associated with progression-free survival and overall survival (OS) . Results: In the overall cohort, the median age at diagnosis was 57 (range, 23-87) years, with a male/female ratio of 1.08:1. Neurological dysfunction (71.2%) and intracranial hypertension (57.7%) were common clinical manifestations. The tumors involved the deep brain tissue and presented as multifocal lesions. Treatment efficacy was evaluable in 49 patients, with a median follow-up of 23 (95% CI: 8.6-37.4) months. The 2- and 5-year PFS rates were 56.4% (95% CI: 42.2%-68.3%) and 36.3% (95% CI: 17.3%-53.4%), respectively, whereas the OS rates were 75.5% (95% CI: 61.7%-87.2%) and 66.0% (95% CI: 43.9%-78.3%), respectively. By univariate Cox regression analysis, age >60 years (HR=3.436, 95% CI: 1.008-11.710, P=0.049) and Memorial Sloan-Kettering Cancer Center grade 3 tumor (HR=22.10, 95% CI: 4.736 - 103.400, P< 0.001) were prognostic factors for worse OS, whereas auto-hematopoietic stem cell transplantation (HSCT) as consolidation therapy was significantly associated with longer OS (HR=0.223, 95%CI: 0.077-0.643, P=0.006). By multivariate Cox regression analysis, high-dose methotrexate chemotherapy (HR=0.082, 95%CI: 0.008-0.873, P=0.038) and auto-HSCT (HR=0.151, 95%CI: 0.030-0.747, P= 0.020) were independent predictors of prolonged OS. Conclusion: The prognosis was poor in patients with PCNSL who are elderly and those at high risk according to risk stratification. Adopting treatment regimens containing high-dose methotrexate and performing auto-HSCT can improve survival in patients with PCNSL.

Objective: To analyze the clinical characteristics, treatment response, and prognosis of patients newly diagnosed with immunoglobulin A multiple myeloma (IgA MM), and to ascertain whether the IgA isotype remains a poor prognostic factor in the bortezomib era. Methods: This study retrospectively enrolled 155 patients newly diagnosed with IgA MM and 420 with non-IgA MM admitted to the Department of Hematology, the First Affiliated Hospital of Nanchang University from March 2014 to December 2021. We compared the two groups in terms of their clinical characteristics, prognoses, and progression-free survival (PFS) and overall survival (OS) following different treatment regimens. Results: Compared with the non-IgA group, the IgA group presented with more aggressive clinical features, including a higher proportion of patients with hemoglobin<85 g/L (61.3% vs 51.4%, P=0.035), extramedullary manifestations (20.0% vs 11.4%, P=0.008), and gain/amp (1q21) (48.6% vs 36.7%, P=0.032). Efficacy analysis revealed a lower overall response rate (ORR) in the IgA group than in the non-IgA group (83.2% vs 92.4%, P=0.001). Among patients treated with bortezomib-based regimens, the ORR was 91.2% in the IgA group and 94.8% in the non-IgA group, but the difference was nonsignificant (P=0.146). Survival analysis showed that the median PFS and OS were significantly shorter in the IgA group compared with the non-IgA group[23.5 (95% CI: 17.4-29.5) months and 48.8 (95% CI: 30.1-67.5) months vs 40.7 (95% CI: 33.8 - 47.6) months and not reached, respectively; P<0.001 and P=0.002]. In the subgroup of patients who received bortezomib-based therapy without subsequent autologous hematopoietic stem cell transplantation (auto-HSCT), the PFS and OS were significantly shorter in the IgA group compared with the non-IgA group[25.4 (95% CI: 18.7-32.1) months and 53.5 (95% CI: 35.4-71.6) months vs 41.0 (95% CI: 33.7-48.3) months and not reached; P=0.001 and P=0.011]. In patients who underwent bortezomib-based induction therapy followed by auto-HSCT, the 1-, 3-, and 5-year OS rates for the IgA group were 96%, 81%, and 81%, respectively, compared with 93%, 89%, and 79% for the non-IgA group, but the difference was nonsignificant (P=0.758) . Conclusion: In the bortezomib era, IgA MM is still associated with a poorer overall prognosis than non-IgA MM, likely due to its inherent high-risk biological characteristics. Although bortezomib-based regimens effectively improve the treatment response, they fail to completely bridge the survival gap between the two disease isotypes. Therefore, bortezomib-based therapy followed by auto-HSCT may be a key strategy to overcome the poor prognosis of IgA MM, potentially enabling these patients to achieve long-term survival comparable to that of their non-IgA counterparts.

Plasma cell leukemia (PCL) is a rare and highly aggressive form of plasma cell dyscrasia, distinguished by its rapid clinical course and dismal prognosis. This guideline is intended to offer clinicians evidence-based, comprehensive recommendations encompassing diagnostic criteria, risk stratification, therapeutic approaches-including frontline treatment, hematopoietic stem cell transplantation, and the incorporation of novel therapeutic agents-as well as protocols for long-term follow-up. The overarching objective is to promote standardized clinical management and ultimately enhance both survival outcomes and quality of life for patients diagnosed with PCL.

Hemophilia is an X-linked recessive inherited hemorrhagic disease primarily caused by reduced activity or deficiency of coagulation factor Ⅷ (FⅧ) or coagulation factor Ⅸ (FⅨ). Depending on the specific coagulation factor deficiency, it is classified into two types: hemophilia A (caused by F Ⅷ deficiency) and hemophilia B (caused by F Ⅸ deficiency), each attributed to gene mutations in their respective coagulation factors. Among these, hemophilia A is the most prevalent, accounting for approximately 80% of all hemophilia cases. In recent years, the advent of novel therapeutic strategies-including long-acting coagulation factor products, non-factor therapies, and gene therapy-has ushered hemophilia into a new era of treatment. Several of these innovative products have been approved for marketing in China, marking a significant improvement in treatment outcomes for patients with hemophilia. To standardize clinical practices amid these new treatment modalities and evolving therapeutic concepts, the Thrombosis and Hemostasis Group of the Hematology Branch of the Chinese Medical Association and the Chinese Hemophilia Collaboration Group have collaborated to develop relevant guidelines. These guidelines aim to provide guidance for domestic medical professionals engaged in hemophilia diagnosis and treatment, ensuring the delivery of standardized, high-quality care.

Objective: To evaluate the long-term efficacy and safety of recombinant coagulation factor Ⅷ (Octocog alfa) in Chinese patients with hemophilia A (HA) enrolled in the International Antihemophilic Factor Hemophilia A Outcome Database (AHEAD) study (NCT02078427) . Methods: Enrollment of Chinese patients in the AHEAD study was completed by January 2021, and data were collected up to July 15, 2022. This study primarily assessed patients in terms of the Gilbert score, global gait score within the Hemophilia Joint Health Score (HJHS), annualized bleeding rate (ABR), annualized joint bleeding rate, and adverse events. Results: A total of 168 male patients were included in this study, of which 113 received prophylactic treatment and 53 received on-demand treatment. The average age of the patients was 21.4±13.37 years. Compared with baseline, the global gait score within HJHS significantly decreased during the 1-year follow-up in patients with moderately severe HA in the prophylactic treatment group (P=0.01) and on-demand treatment group (P=0.008). The mean reduction in Gilbert score was greater in the prophylactic treatment group than in the on-demand treatment group (28.6% vs 8.2%). The average ABR decreased significantly during the 1-year follow-up (3.70 vs 7.78, P=0.01) in the prophylactic treatment group, particularly in patients with severe HA (2.14 vs 8.98, P=0.006) and pediatric patients (2.1 vs 4.73, P=0.03). The ABR score also decreased significantly in the moderate-dose prophylactic treatment group (P=0.015). During the 1-year follow-up, 25 patients (14.9%) reported 39 adverse events, with only one patient developing treatment-related F Ⅷ inhibitor. Conclusion: Joint mobility improved in patients receiving either prophylactic or on-demand Octocog alfa. Bleeding episodes significantly reduced in patients receiving prophylactic treatment, particularly in pediatric patients and those with severe HA.

Objective: To explore differences in the efficacy and safety of ruxolitinib in patients with myelofibrosis by age and to identify prognostic factors by analyzing clinical features and characteristics of chromosomes and gene mutations. Methods: This study retrospectively analyzed 188 patients with myelofibrosis who received ruxolitinib in the Department of Hematology, Qilu Hospital, Shandong University from January 1, 2017, to July 1, 2024. According to age at diagnosis, the patients were divided into the middle-aged group (≤55 years), young elderly group (56-65 years), and elderly group (>65 years). Clinical features, the characteristics of chromosomes and gene mutations, and the efficacy and safety of ruxolitinib treatment were compared across the three age groups. Independent factors influencing overall survival were identified through Cox proportional risk regression analysis. Results: Before treatment, the elderly group had more underlying comorbidities, a heavier symptom burden, higher leukocyte count, higher proportion and frequency of JAK2 mutations, and lower proportion of CALR mutations. The incidence of nondriver gene mutations was significantly higher in the young elderly group. After ruxolitinib treatment, the degree of reduction in spleen size did not differ significantly among the three groups. The length of the palpable spleen below the left costal margin reduced by more than 50% from baseline in 50.9% (27/53) of the patients in the middle-aged group, 43.5% (27/62) in the young elderly group, and 45.5% (20/44) in the elderly group (P=0.720). No significant difference was observed among the three groups in the degree of reduction in Myeloproliferative Neoplasm Symptom Assessment Form (10-item version) score (P=0.153), with a reduction in total symptom score by more than 50% achieved by 54.0% (27/50), 60.3% (41/68), and 66.7% (34/51) of the patients from the three groups, respectively (P=0.429). The most common hematological adverse events were anemia and thrombocytopenia, while the most common nonhematological adverse events were electrolyte disturbance, elevated transaminase activity, and pulmonary infection. Multivariate analysis indicated that in ruxolitinib-treated patients with myelofibrosis, poor overall survival was independently predicted by increased age, reduced hemoglobin, percentage of bone marrow blasts ≥ 1%, absence of JAK2 mutations, chromosomal abnormalities, ≥2 high-molecular-risk mutations, and TP53 mutations. Conclusions: Patients with myelofibrosis stratified by age exhibited heterogeneous clinical features and gene mutation profiles but similar efficacy of ruxolitinib treatment and occurrence of adverse events.

A 64-year-old male patient with hemophilia A was scheduled for the surgical removal of a pulmonary mass. Preoperative evaluation revealed that the coagulation factor Ⅷ (FⅧ) activity was 0.5%, with an F Ⅷ inhibitor level of 32 BU/ml; the R value could not be detected on the thromboelastogram. Thoracoscopic lobectomy was successfully completed. On the day of the operation and the first day after the operation, 6 mg of recombinant activated coagulation factor Ⅶ (rFⅦa) was intravenously administered every 6 h. On postoperative day 1, the patient's blood pressure dropped and the HGB gradually declined from 102 g/L to 65 g/L. Chest X-ray revealed a large amount of pleural effusion on the left side, and urgent thoracoscopic thoracic exploration was performed. A total of 3200 mL fresh blood was cleared, and a thoracic drainage tube was placed. On postoperative day 2, the rFⅦa dose was increased to 6 mg, which was intravenously administered every 4 h, and concentrated red cells were intermittently infused to correct anemia. Four days later, due to the inability to obtain rFⅦa, PCC (50 IU/kg every 8 hours) was administered. Additionally, treatment with methylprednisolone (40 mg/d) and cyclophosphamide (200 mg, every 2 weeks) was initiated to remove FⅧ inhibitors. The thoracic drainage tube was removed on postoperative day 9, and the patient was successfully discharged 3 weeks later.

Objective: To investigate the combined therapeutic role of the AKT inhibitor MK2206 and Ruxolitinib in treating Myeloproliferative Neoplasms (MPN) driven by a calreticulin (CALR) gene mutation. Methods: ① Murine bone marrow c-kit(+) cells were isolated by sacrificing mice and harvesting bone marrow from the femur, tibia, and ilium for subsequent c-kit(+) cell sorting. ② A CALR transplantation mouse model was established. GFP-tagged retroviral vectors containing either the CALR gene mutation or the migR1 control were constructed, packaged in Platinum-E cells, and used to transduce murine bone marrow c-kit(+) cells. These transduced cells were then transplanted into lethally irradiated female recipient mice via tail vein injection. ③ Following successful engraftment, the mice were randomly assigned to four treatment groups for intragastric administration. Complete blood counts were monitored periodically, and the spleen size and weight of transplanted mice were measured. ④ Flow cytometry was used to quantify the proportions of GFP(+) tumor cells, megakaryocytic lineage cells, and hematopoietic stem cells in both splenic and bone marrow tissues. Histopathological examination was performed to evaluate the degree of tumor cell infiltration in these organs. Results: ① Following gavage treatment, peripheral blood platelet (PLT) and white blood cell counts were significantly lower in the combined AKT inhibitor MK2206 and Ruxolitinib group compared to the MK2206, Ruxolitinib, and control groups (P<0.05). ② In comparison with the MK2206 and Ruxolitinib monotherapy groups, the combination therapy group exhibited a significant reduction in spleen weight and a marked improvement in splenomegaly at 30 weeks post-transplantation (P<0.05). ③ After four weeks of continuous treatment, combined administration resulted in a significant decrease in the proportion of megakaryocytic lineage cells and GFP(+) tumor cells in the bone marrow and spleen (P<0.05). Additionally, the proportion of hematopoietic stem cells in the bone marrow was also significantly reduced (P<0.05). ④ Histopathological analysis (H&E staining) of bone marrow and spleen tissues confirmed that the combined regimen decreased both tumor cell infiltration and the proportion of abnormal megakaryocytes in these organs. Conclusion: The combination of AKT inhibitor MK2206 and Ruxolitinib is effective at significantly ameliorating disease symptoms and reducing tumor infiltration in vivo in mice with a myeloproliferative tumor transplantation driven by a CALR gene mutation.