Burkitt lymphoma (BL) is a rare and highly aggressive B-cell non-Hodgkin lymphoma. While targeted combination chemotherapy can be effective, it is associated with a high rate of relapsed or refractory disease and a pronounced propensity for central nervous system (CNS) involvement. Currently, novel therapies such as chimeric antigen receptor T-cell (CAR-T) therapy have not demonstrated established efficacy in BL. Given the poor prognosis and the challenge of managing relapsed/refractory BL, the use of bispecific antibodies, specifically glofitamab, as employed in this case, has yielded a favorable therapeutic outcome. This is particularly noteworthy in the present case, given the patient’s documented CNS infiltration. After the failure of first-line treatment in this case, the combination of glofitamab and a Bruton’s tyrosine kinase inhibitor (BTKi) was used for six cycles, which significantly improved the patient’s CNS infiltration and achieved a long remission period. This provides an opportunity to try glofitamab in the treatment of CNS lymphoma, and we look forward to its confirmation in more BL patients.

INTRODUCTION:Diffuse large B-cell lymphoma (DLBCL) is mostly curable by chemotherapy, but p53 mutations limit the therapeutic effect of DLBCL. Although chimeric antigen receptor (CAR) T cells have made revolutionary progress in the treatment of DLBCL, p53 mutations still lead to drug resistance and/or relapse of DLBCL, affecting the prognosis of lymphoma. Therefore, the project aims to explore additional therapeutic strategies to improve the prognosis of DLBCL with p53 mutations. METHODS:We investigated the correlation between XPO1 and mut-P53 employing qRT-PCR, WB, CCK8 and flow cytometry. Then, we conduct XPO1 inhibitor (KPT-330) to explore the apoptotic effect on DLBCL. Through the TCGA database, there is a clear correlation between XPO1-related genes and the PI3K-AKT pathway. RESULTS:In this study, we showed that XPO1 inhibitor (KPT-330) synergized with CAR-T to reduce the viability of DLBCL and enhance the killing effect of CAR-T cells. As expected, KPT-330 combined with CAR-T therapy slowed tumor growth and reduced tumor burden in DLBCL with p53 mutations. Mechanistically, XPO1 inhibitor KPT-330 can cooperate with CAR-T in the treatment of DLBCL by activating the PI3K pathway. Then, in vitro cytotoxicity assays revealed that the KPT-330 combined with CAR-T group significantly enhanced the secretion of effector cytokines IFN-γ, TNF-α, and IL-2, and activated the immune system. CONCLUSIONS:The XPO1 inhibitor KPT-330 exerts anti-cancer effects through stabilizing p53 and inhibiting the PI3K-AKT pathway, providing a molecular basis for DLBCL treatment. We may provide a potential promising combination therapy for the treatment of DLBCL with p53 mutations.

Introduction Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder characterized by complement-mediated hemolysis, thrombophilia, and bone marrow failure. Despite anti-C5 therapy (e.g., eculizumab), many patients remain anemic due to residual intravascular hemolysis and C3-mediated extravascular hemolysis (EVH). HSK39297, a novel oral Factor B inhibitor, targets proximal complement activation and enables a once-daily administration regimen, offering potential advantages over existing therapies. This phase 2 trial evaluated the efficacy and safety of HSK39297 monotherapy in complement inhibitor- naïve PNH patients. Methods In this open-label, multicenter study (NCT06561841), 47 adults with PNH (granulocyte clone >10%, lactate dehydrogenase [LDH] >1.5× upper limit normal [ULN], hemoglobin [Hb] <100 g/L) were randomized 1:1:1 to receive HSK39297 (cohort A: 75 mg/125 mg twice daily [BID], cohort B: 100 mg BID, or cohort C: 200 mg once daily [QD]) for 24 weeks. The primary endpoint was the proportion of patients achieving Hb increase of ≥20 g/L without red blood cell (RBC) transfusions between weeks 4 and 24. Secondary endpoints included LDH reduction > 60% or normalization, changes in Hb levels, reticulocyte count, indirect bilirubin, PNH clone size, C3 fragment deposition, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scores, and safety. Pharmacokinetics and pharmacodynamics were assessed. Results At week 24, 42 of 47 patients (89.4%) met the primary endpoint (cohort A: 87.5%; B: 86.7%; C: 93.8%). Transfusion avoidance was achieved in 95.7% of patients. Mean Hb increased by 50.7 g/L. LDH levels reduced by ≥60% or normalized in all patients (47/47, 100%). C3d+ RBC levels remained low (0.34% at week 24). Consistent improvements were observed in other markers of hemolysis and FACIT-Fatigue scores. Adverse events (AEs) occurred in 72.3% of patients ,mostly of which were grade ≤2（CTCAE5.0）. 59.6% of patients experienced drug-related AEs, with headache (34.0%) being the most frequently reported. No breakthrough hemolysis or thromboembolic events were reported. The 200 mg QD cohort showed sufficient exposure to sustained complement inhibition at the trough. Conclusions HSK39297 monotherapy significantly improved hematologic and clinical outcomes in complement inhibitor- naïve PNH patients, demonstrating robust efficacy across all doses and a favorable safety profile. The 200 mg QD regimen demonstrated optimal efficacy and pharmacokinetics and is therefore proposed for further investigation in phase 3 trials.

Abstract Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease with limited treatment options. The COMMODORE 2 study demonstrated that the novel C5 inhibitor crovalimab had comparable safety and non-inferior efficacy to eculizumab. We evaluated the safety and efficacy of crovalimab compared with eculizumab in the Chinese subpopulation of the global COMMODORE 2 study. Adult patients with PNH without previous complement inhibitor therapy were randomized (2:1) to crovalimab or eculizumab for 24 weeks. The co-primary endpoints were the proportions of patients achieving hemolysis control from Weeks 5–25 and those with transfusion avoidance from baseline to Week 25. The secondary endpoints included the proportion of patients with breakthrough hemolysis and hemoglobin stabilization from baseline to Week 25 and the mean change from baseline in FACIT-Fatigue score at Week 25. Safety data were assessed from baseline to the clinical cut-off (16 November 2022). The demographic and baseline characteristics of the 81 patients included (eculizumab: 27; crovalimab: 54) were well-balanced. In the crovalimab and eculizumab arms, respectively, hemolysis control was achieved in 88.3% and 86.8%, transfusion avoidance in 72.2% and 74.1%, hemoglobin stabilization in 72.2% and 70.4%, and breakthrough hemolysis in 5.6% and 11.1%. The FACIT-Fatigue score improvement was greater with crovalimab. Adverse events (81.5% vs. 88.9%) and grade 3–5 adverse events (24.1% vs. 33.3%) were less frequent with crovalimab. Over 24 weeks, 91% of patients achieved complete terminal complement inhibition with crovalimab. Crovalimab demonstrated at least comparable treatment performance and acceptable safety in Chinese patients with PNH. Clinical trial registration ClinicalTrials.gov identifier NCT04434092 (study registration was first posted on 16th June 2020).

Background Aplastic anemia (AA) is a severe hematological disorder caused by hyperactivated T cell-mediated hematopoietic failure. It is characterized by hematopoietic stem cell deficiency and hypocellular hematopoiesis in the bone marrow (BM). Ferroptosis, a specific type of programmed cell death, is defined by iron-dependent lipid peroxidation, which has garnered the attention of researchers due to its unique role and biological importance in various diseases. However, the correlation between immunological imbalance-induced ferroptosis and the mortality of hematopoietic stem cells within the BM microenvironment in AA is unclear. Resveratrol (RSV) is crucial in activating NRF2, hence influencing the onset and progression of diseases by regulating ferroptosis. This study aimed to investigate the roles and molecular mechanisms of RSV in the hematopoietic recovery of AA regarding ferroptosis.Methods We measured some biomarkers in AA mice and IFN-gamma-treated 32D cells, representing AA syndromes and ferroptosis features. Furthermore, in RSV-treated 32D AA cells, cell activity, cell apoptosis, mitochondrial membrane potential, mitochondrial membrane permeability, and intracellular levels of MDA, ferrous iron, 4-HNE, GSH, ROS, and lipid peroxidation were assessed. Subsequently, additional in vitro and in vivo experiments were performed to investigate the mechanisms by which RSV effectively regulates NRF2 stability, further inhibiting ferroptosis in AA.Results We demonstrated that ferroptosis contributes to the occurrence and development of AA disease. RSV dose-dependently inhibits ferroptosis in 32D AA cells by targeting GPX4 expression, enhancing the cell activity of hematopoietic BM cells. Mechanically, RSV significantly increases NRF2 phosphorylation through the PI3K/AKT/mTOR signaling pathway, which maintains NRF2 stability to promote the GPX4 metabolic pathway in AA. Protein levels of p-AKT, p-mTOR, p-NRF2, and GPX4 were markedly increased in BM cells in RSV-treated AA mice, resulting in the suppression of AA development.Conclusion Our data demonstrate that RSV effectively inhibits ferroptosis in AA or IFN-gamma-treated 32D cells by targeting the PI3K/AKT/mTOR signaling pathway, which enhances NRF2-mediated GPX4 transcription, thereby ameliorating AA symptoms in vitro and in vivo. This study concludes that RSV is a potential therapeutic drug for ferroptosis-related AA treatment.

BACKGROUND:Thrombotic microangiopathy (TMA) is an acute syndrome characterized by microangiopathic hemolytic anemia, thrombocytopenia, and multi-organ dysfunction due to the microcirculation of platelet thrombi. Cancer-associated TMA is a rare and fatal complication, which often occurs during cancer remission. It is frequently misdiagnosed because of limited clinical awareness. CASE SUMMARY:A middle-aged female patient presented to our clinic with a 15-days history of back pain, 15 months post-gastrectomy. Cancer-associated TMA was confirmed through bone marrow aspiration, biopsy, and imaging. The patient received intermittent transfusions, fluids, nutrition, and microcirculation therapy with partial coagulation improvement. The family refused intensive care unit admission and plasma exchange, preferring palliative care. The patient died of cerebral hemorrhage and herniation due to disease progression. This case indicates that TMA may serve as an early manifestation of various malignancies, particularly gastric cancer. However, it is often misdiagnosed. Its pathogenesis is not well understood and needs to be further investigated. Currently, no standardized treatment have been developed. Plasma exchange is the only intervention available, though other therapies may also be effective. CONCLUSION:In this case of gastric signet-ring cell carcinoma complicated by TMA, the patient achieved transient remission with supportive care but died following treatment discontinuation. Further studies are needed to elucidate the pathological mechanisms and therapeutic strategies for cancer-associated TMA.

Chimeric antigen receptor (CAR-T) cell therapy has been widely used in haematological malignancies and has achieved remarkable results. However, two major toxicities of CAR-T-cell therapy, cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, have been reported in many studies and often require hospitalization. There is evidence that CAR-T-cell therapy is being increasingly used clinically, so it is important to pay attention to its serious adverse events that may be life-threatening. In this review, we provide a detailed discussion of the clinical manifestations, classification, risk factors, and management and treatment of serious adverse events to provide theoretical support for clinicians to manage such cases. Although the clinical application of CAR-T cells continues to expand, adverse events associated with CAR-T-cell therapy are inevitable. With the identification of risk factors and the application of various new therapeutic approaches, the incidence and severity of these adverse events can be effectively controlled.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening, complement-mediated hematologic disorder. Pregnancy, often a complement-activating event, is associated with poor outcomes in patients with untreated PNH and other complement-mediated diseases. Crovalimab (PiaSky®) is a next-generation C5 inhibitor with every-4-week subcutaneous maintenance dosing, with the possibility for self-administration by the patient or caregiver, after proper training. Crovalimab is indicated for the treatment of PNH and is currently being evaluated for the treatment of other complement-mediated diseases. Here we present data on the use of crovalimab during pregnancy, with the aim of characterizing pregnancy outcomes after crovalimab exposure, using both animal and clinical trial data. As part of the non-clinical safety evaluation, an enhanced prenatal and postnatal development study assessed pregnant cynomolgus monkeys who were given an intravenous loading dose of 100 mg/kg crovalimab on Gestation Day 20 followed by weekly subcutaneous injections of up to 100 mg/kg until parturition. The dams and infants were observed untreated for 6 months. A cynomolgus monkey model was chosen for crovalimab toxicity assessment due to the high C5 sequence homology (95.9%) to human C5, leading to comparable complement binding affinity and inhibitory effects. A retrospective review of pregnancies in patients treated with crovalimab in the Phase I–III clinical trial program for crovalimab was performed, including patients from the COMPOSER (NCT03157635), and COMMODORE 1 (NCT04432584), 2 (NCT04434092), and 3 (NCT04654468) trials (PNH), the COMMUTE-a (NCT04861259) and -p (NCT04958265) trials (atypical hemolytic uremic syndrome [aHUS]), and the CROSSWALK-a (NCT04912869) trial (sickle cell disease [SCD]). In the cynomolgus monkey reproductive toxicity study, there were no adverse effects of crovalimab on pregnancy with doses up to 100 mg/kg. Additionally, there were no adverse effects on the viability, growth, and development of the infants. Exposures were up to 14 times the human exposure at the maximum recommended human dose, based on area under the concentration-time curve. In the clinical trial program, there were eight pregnancies reported, which all occurred after patients started treatment with crovalimab; six in patients with PNH, one in a patient with aHUS, and one in a patient with SCD. Among these eight patients, three (all with PNH) provided consent to share data about the pregnancies. One patient continued crovalimab throughout the pregnancy. The patient experienced a Grade 3 adverse event of pre-eclampsia at Gestational Week 31, deemed unrelated to crovalimab by the investigator. The patient gave birth by Cesarian section at Gestational Week 36; the infant was born with dysmaturity (1.96 kg at birth), which was deemed related to the mother's pre-eclampsia. The pre-eclampsia was considered resolved the same day. The infant was hospitalized for several days but was discharged after stabilizing. Crovalimab treatment was continued, with no change in treatment due to pre-eclampsia. Elective abortions were performed for the other two pregnancies with data available, both within the first 2 months and with no reported adverse events related to crovalimab. Crovalimab treatment was continued in both cases. Adverse outcomes, including hypertensive disorders such as pre-eclampsia, are common in complement-mediated diseases; therefore, pregnant patients being treated for such diseases should be monitored. Although data on crovalimab treatment during pregnancy are limited in patients with PNH, data from the reproductive toxicity study in pregnant animals and clinical trial data suggest no adverse effect of crovalimab treatment on pregnant mothers or fetuses, consistent with data from other C5 inhibitors. As untreated PNH in pregnancy is associated with adverse outcomes, continuation of crovalimab treatment in patients with PNH who become pregnant should be considered.

OBJECTIVE:To analyze the clinical characteristics, treatment effect and prognosis of patients with non-Hodgkin lymphoma (NHL) complicated by hypercalcemia. METHODS:The clinical features, treatment and prognosis of 47 patients with NHL complicated by hypercalcemia in Ningde Municipal Hospital of Ningde Normal University and Affiliated Hospital of Nantong University from January 2018 to January 2023 were retrospectively analyzed. RESULTS:Among the 47 lymphoma patients, 33 cases were T-cell NHL, 14 cases were B-cell NHL. The median serum calcium level of the 47 patients was 3.10 (2.77-4.86) mmol/L, with 27 cases (57.4%) experiencing mild hypercalcemia (2.75-3.00 mmol/L), 8 cases (17.0%) experiencing moderate hypercalcemia (3.00-3.50 mmol/L), and 12 cases (25.5%) experiencing severe hypercalcemia (>3.50 mmol/L). All 47 patients were treated with hydration, alkalization, diuresis, etc. 32 cases (68.1%) received combination chemotherapy, 21 cases (44.7%) received salmon calcitonin treatment, and 3 cases were treated with denosumab in 5 patients with renal insufficiency. After treatment, 38 patients' serum calcium gradually returned to normal, with a median recovery time of 6 (1-18) days, while 9 patients still failed to recover their serum calcium after treatment and all died within 1 month. 32 patients undergoing combination chemotherapy were evaluated for efficacy after 2-4 courses of chemotherapy. Among them, 8 cases (25.0%) achieved complete response (CR), 11 cases (34.4%) achieved partial response (PR), 7 cases (21.9%) showed stable disease (SD), and 6 cases (18.8%) showed progressive disease (PD). The median follow-up time was 10 months. There were 13 cases of disease progression after combination chemotherapy and a total of 28 deaths. The survival time ranged from 0.8 to 23.7 months, and the median progression time was 4.9 months. Multivariate Cox regression analysis showed that the T-cell NHL, blood calcium >3.5 mmol/L, and no decrease in blood calcium after treatment were independent risk factors for the OS, and the T-cell NHL was independent risk factors for the PFS. CONCLUSION:NHL complicated by hypercalcemia has a poor prognosis, and hypercalcemia can be used as one of the indicators reflecting the tumor burden. Patients with NHL complicated by hypercalcemia should be given more clinical attention and treated actively.

Crovalimab is a novel C5 complement inhibitor that enables rapid and sustained C5 inhibition with subcutaneous, low-volume self-administration every 4 weeks. COMMODORE 2 (NCT04434092) is a global, randomized, open-label, multicenter, phase 3 trial evaluating the non-inferiority of crovalimab versus eculizumab in patients with paroxysmal nocturnal hemoglobinuria not previously treated with C5 inhibition. C5 inhibitor-naive patients with lactate dehydrogenase (LDH) ≥2 × upper limit of normal (ULN) were randomized 2:1 to crovalimab or eculizumab. Co-primary efficacy endpoints were proportion of patients with hemolysis control (centrally assessed LDH ≤1.5 × ULN) and proportion with transfusion avoidance. Secondary efficacy endpoints were proportions of patients with breakthrough hemolysis, stabilized hemoglobin, and change in FACIT-Fatigue score. The primary treatment period was 24 weeks. Two hundred and four patients were randomized (135 crovalimab; 69 eculizumab). Crovalimab was non-inferior to eculizumab in the co-primary endpoints of hemolysis control (79.3% vs. 79.0%; odds ratio, 1.0 [95% CI, 0.6, 1.8]) and transfusion avoidance (65.7% vs. 68.1%; weighted difference, -2.8 [-15.7, 11.1]), and in the secondary efficacy endpoints of breakthrough hemolysis (10.4% vs. 14.5%; weighted difference, -3.9 [-14.8, 5.3]) and hemoglobin stabilization (63.4% vs. 60.9%; weighted difference, 2.2 [-11.4, 16.3]). A clinically meaningful improvement in FACIT-Fatigue score occurred in both arms. Complete terminal complement activity inhibition was generally maintained with crovalimab. The safety profiles of crovalimab and eculizumab were similar with no meningococcal infections. Most patients who switched from eculizumab to crovalimab after the primary treatment period preferred crovalimab. These data demonstrate the positive benefit-risk profile of crovalimab.

Eltrombopag combined with immunosuppressive therapy (IST) was superior to IST alone for severe aplastic anemia (SAA) in the previous studies. But in China, horse antithymocyte globulin (hATG) is not available, instead, we use rabbit ATG (rATG). Here, we compared the efficacy and safety of IST (rATG combined with cyclosporine) combined with or without eltrombopag for the first-line treatment of SAA and very severe aplastic anemia (VSAA). A total of 371 patients in ten institutions in China from April 1, 2017 to December 1, 2022 were enrolled. The overall response (OR) rate at 3 months (54.2

Objectives POEMS syndrome is a rare disorder which has been increasingly recognized. The clonal origin is controversial. Some people argue that POEMS syndrome originates from abnormal plasma cell clones. So, treatment frequently targets the plasma cell clone. Nevertheless, others believe that both plasma cells and B cells can be the potential culprit in POEMS syndrome. Methods A 65-year-old male came to the emergency department of our hospital with the complaints of bilateral soles numbness and weight loss for half a year, abdominal distension for half a month, and chest tightness and shortness of breath for one day. He was then diagnosed as POEMS syndrome complicated with monoclonal B-cell lymphocytosis (non-CLL type). A standard bendamustine plus rituximab (BR) regimen combined with low dose of lenalidomide was administered. Results After four cycles of treatment, the ascites of the patient was absent and the neurological symptom disappeared. The renal function, the IgA level, and the VEGF level all returned to normal. Discussion POEMS syndrome, a multi-system disorder, is easily misdiagnosed. The clonal origin of POEMS syndrome is controversial and needs further study. For now, there are no approved treatment regimens. Treatments mainly target the plasma cell clone. This case suggested that other therapy besides anti-plasma cell treatment may also be effective in POEMS syndrome. Conclusion We report a patient with POEMS syndrome who achieved complete response after treatment with the combination of a standard BR regimen and low dose of lenalidomide. POEMS syndrome's pathological mechanisms and therapies warrant further studies.

Multiple myeloma (MM) is a fatal hematological malignancy and does not have adequate prognostic indicators. Previous studies indicate that CEP72 is closely related to tumorigenesis and tumor progression. However, the expression and function of CEP72 in multiple myeloma have yet to be elucidated.

Topic: 11. Bone marrow failure syndromes incl. PNH - Biology & Translational Research Background: Aplastic anemia (AA) is a typical human bone marrow failure syndrome, which is due to immune attack of hematopoietic stem and progenitor cells (HSPCs) by auto-reactive T cells for most patients. Epag（eltrombopag） is a novel thrombopoietin receptor (TPO-R) agonist that has been suggested in many studies to promote hematopoiesis, alleviating the low blood platelet counts with chronic immune thrombocytopenia, possibly by the following mechanisms: stimulation of hematopoietic stem progenitor cell proliferation; promoting a more tolerizing environment via an increase in regulatory T and B cells; modulating immunity by a decreased release of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) and a increased release of transforming growth factor-β (TGF-β); mobilizing intracellular iron, resulting in a decrease in total iron burden. Aims: Studies have shown that Epag can improve the early response to IST treatment, shorten the time period of pancytopenia, and reduce side effects, which makes Epag converted from second-line therapy to first-line therapy. However, because of the slow onset of Epag, the need for long-term maintenance therapy, and the limited efficacy of monotherapy, further exploration of its mechanism is warranted, resulting in a extensive clinical application. Methods: In order to further clarify the mechanism of Epag in the treatment of AA, we used BM failure mice and 32D cells. A new possible mechanism of Epag in the treatment of AA has been demonstrated through in vitro and in vivo trials. Results: Based on our experiments, it is significantly demonstrated that Epag has failure to restore blood counts and mononuclear cells in bone marrow and spleen of BM failure mice, mainly altering the propotion of the T lymphocyte subsets (such as CD4+T, CD8+T, Treg cells) and CD8+/CD4+T ratio. Our data revealed that Epag had inhibitory effect on the proliferation and induced effect the apoptosis of wild type 32D cells induced by IFN-γ in a concentration-dependent manner. Interstingly, in IFN-γ-induced 32D cells with hTPO receptor overexpression, Epag had no obvious effect on cell apoptosis. This shows that hTPO receptor plays a key role in the function of Epag treatment. To further reveal the mechanism of Epag effect, the stability and ubiquitination of Akt protein were performed. Our results demonstrated that Epag significantly decreased the stability of Akt protein via the proteasome pathway, ultimately resulting in the inhibition of cell growth and proliferation in AA mice. Summary/Conclusion: In summary, the regulation of hematopoiesis by Epag is a complex network structure, with distinct positive and negative regulation in different species and at different times. Epag lacks the promotion of hematopoiesis through the TPO-R dependent pathway, and also further activated the cytotoxic T cells of BM failure mice. Keywords: T cell, Akt, Anemia

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Central lymphoma includes two types, primary and secondary. Current treatment regiments are not effective in many patients. zanubrutinib is a BTK inhibitor and pomalidomide is an immunomodulator, which have been reported to be used in the treatment of central nervous system lymphoma. Aims: To investigate the efficacy and safety of zanubrutinib combined with pomalidomide in the treatment of primary or secondary central nervous system lymphoma. Methods: A total of 8 patients diagnosed with primary or secondary central nervous system lymphoma from October 2021 to January 2023 were included. They received zanubrutinib combined with pomalidomide based regimen for at least 2 courses, and the short-term efficacy and safety were analyzed. Results: Among the 8 patients, 7 were effective after 2 courses of treatment, 1 was lost to follow-up. 7 remained effective after 4 courses of treatment,2 patients had central recurrence after 5 courses of treatment, all of which were secondary central nervous system lymphoma involving cerebrospinal fluid, and 1 patient died of coronavirus disease (COVID-19） infection. The adverse reactions were mainly hemocytopenia and pulmonary infection. One case of hypokalemia was aggravated. The adverse events were controllable and improved after symptomatic treatment. Summary/Conclusion: The regimen based on zanubrutinib and pomalidomide has certain efficacy in the treatment of primary or secondary central nervous system lymphoma, and the combination of zanubrutinib and pomalidomide can further improve the response rate and remission time. However, due to the limited cases, the strength of relevant clinical suggestions needs to be further confirmed by expanding the sample size and multi-center studies. Keywords: Immunomodulation, Lymphoma therapy, Bruton’s tyrosine kinase inhibitor (BTKi)

OBJECTIVE:To compare the efficacy of eltrombopag combined with cyclosporine A (CsA) and CsA alone in patients with transfusion-dependent non-severe aplastic anemia (TD-NSAA).METHODS:The clinical data of 76 patients with treatment-naive TD-NSAA in Ningde Municipal Hospital of Ningde Normal University and Affiliated Hospital of Nantong University from December 2017 to June 2021 were retrospectively analyzed. Among them, 45 cases were treated with eltrombopag combined with CsA, and 31 patients with compatible baseline characters were treated with CsA alone. The efficacy of patients between the two groups was compared, and the factors affecting the curative effects were also analyzed.RESULTS:There were significant differences in hematological response (HR) and complete response(CR) rates between the two groups at 3, 6, 12 months, and follow-up endpoint of treatment (P<0.05). With the prolongation of eltrombopag treatment time, the curative effect increased gradually, and the patients achieved more CR and HR rates by the end of the follow-up period. Simultaneously, with the increase in the maximum stable dose of eltrombopag, the HR rate increased gradually. The megakaryocyte count in eltrombopag group was higher than that in control at 6 and 12 months (P<0.05). Compared with the control group, the median time of platelet transfusion independence in eltrombopag group was more shorter (P=0.018), and the median platelets transfusion volume was lower (P=0.009). At 3, 6, 12 months after eltrombopag, the change of platelet in eltrombopag group was higher than that in the control group (P<0.05). Analysis of related factors affecting the efficacy showed that sex, age, iron overload, platelet count before treatment had no effect on the efficacy, and the median maximum stable dosage and the administration period for eltrombopag were related to the curative effect. The patients of eltrombopag group experienced adverse events of varying degrees, but the reactions were mild and mostly tolerated.CONCLUSION:Eltrombopag can effectively improve the hematopoietic response and promote platelet recovery for TD-NSAA patients with relatively more residual hematopoietic cells, and it is safe and well tolerated.

Background. The emergence of dexamethasone (Dex) resistance limits its efficacy. Side population (SP) cells in MM have strong tumorigenicity. Nevertheless, the detailed effect by which SP cells regulate Dex resistance in MP cells has not been completely verified and needs to be further investigated. Methods. SP and MP cells were sorted from RPMI-8226. mRNA expression and cell viability were analyzed using quantitative real-time PCR (qRT-PCR) and MTS assays, respectively. The presence of exosomal lncRNA SNHG16 was verified by transmission electron microscopy, differential ultracentrifugation, and qRT-PCR. Protein expression levels were measured using western blotting. Gain or loss function analyses were performed to demonstrate the role of SNHG16 in the Dex resistance of MP cells. Results. Dex resistance of SP cells was remarkably stronger than that of MP cells. Compared with MP cells, the survival rate and Dex resistance of MP cells cotreated with SP cell-derived exosomes were increased. SNHG16 expression was significantly enhanced in SP cell-derived exosomes compared to MP cell-derived exosomes. SNHG16 expression was remarkably increased in MP cells transfected with OE-SNHG16 vectors, and Dex resistance of MP cells was enhanced. When SNHG16 was silenced in SP cells, the SNHG16 expression was downregulated in both SP cells and SP cell-derived exosomes. SNHG16 expression and Dex resistance were both remarkably downregulated in MP cells treated with SP-si-SNHG16-exosomes compared to MP cells treated with SP-si-NC-exosomes. Conclusion. MM SP cells promote Dex resistance in MP cells through exosome metastasis of SNHG16.

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Relapsed/refractory multiple myeloma(RRMM) is a malignant disease with abnormal proliferation of clonal plasma cells. With the use of autologous stem cell transplantation and new drugs in the first-line therapy, the survival rate of MM patients has improved significantly. However, MM is still an incurable disease and patients will eventually face recurrence. In view of the impact of the Corona Virus Disease 2019(COVID-19), many patients can not get regular treatment. Delaying or even interrupting treatment has become the biggest difficulty in the disease progression of MM. Therefore, it is urgent to seek safe and convenient all-oral chemotherapy regimens. Aims: To evaluate the efficacy and safety of Ixazomib, Pomalomide and dexamethasone(IPD) in the treatment of relapsed/refractory multiple myeloma(RRMM) retrospectively. Methods: We enrolled 11 patients with RRMM who received at least 4 courses of IPD in the Department of Hematology, Affiliated Hospital and Medical School of Nantong University from January 2021 to July 2022, and analyzed the efficacy and safety after medication. Results: The number of presequencing lines in the patients included in the study ranged from 1 to 4, and the main reasons for switching to IPD were relapse, progression, and COVID-19. In ≥4 courses of treatment, the all-oral IPD was discontinued after progression in 3 of 9 patients with evaluable efficacy. Among the 2 patients that in stable disease(SD), one case continued to take medication while another changed to Daratumumab-Ixazomib-dexamethasone(DID) due to their own will. The remaining 5 patients who responded to IPD continued to take medication. Summary/Conclusion: Under the trend of the COVID-19 pandemic, the all-oral IPD treatment has better efficacy and safety, and is more stable and convenient. However, due to the limited cases, the strength of relevant clinical suggestions needs to be further confirmed by expanding the sample size and multi-center studies. Keywords: Relapse, Treatment, Refractory, Multiple myeloma

患者,男,57岁,因"发现右下肢皮肤肿块3个月"于2018年8月22日至我院就诊.行皮肤组织病理活检.免疫组化提示:CD79(+),CD20(+),CD3(-),CD56(-),CD138(-),EB 病毒编码小RNA(-),T细胞胞浆内抗原1(-),颗粒酶B(-),CD5(-),末端脱氧核苷酸转移酶(-),髓过氧化物酶(-),Bcl-2(+),Bcl-6(弱+),c-Myc(+),多发性骨髓瘤癌基因1(Mum-1)(+),CD10(+),Ki-67(80％+),符合弥漫大B细胞淋巴瘤-生发中心型;荧光原位杂交示:c-Myc(-),Bcl-2(-),Bcl-6(-).

目的:探索教学纳入岗位绩效后对教学质量的影响.方法:随机选取2020年6月—8月南通大学附属医院内科实习医生20例作为研究对象,通过OSCE考试评价实习医生岗位胜任能力,通过智慧医教平台,对临床教师的临床教学内容、过程和结果进行精细化管理并评分.自2020年7月开始将教学考核纳入科室及科主任经济绩效考核中,比较各月份实习医生OSCE考试成绩以及教师绩效考核评分.结果:与2020年6月份比较,2020年7月份和8月份学生OSCE问诊(18.20±1.06分、21.70±0.79分)、体格检查(18.80±0.95分、20.60±1.04分)、临床思维(19.80±1.05分、22.20±0.66分)、操作技能(21.50±0.93分、23.00±0.85分)各单项成绩及整体成绩(82.30±0.99分、87.50±0.80分)均稳步升高,差异均具有统计学意义(P<0.05).结论:将临床教学纳入科室及科主任经济绩效考核中可显著提高临床教师教学积极性和教学质量.