Myelodysplastic syndrome (MDS) is a heterogeneous group of myeloid neoplasms characterized by treatment difficulties and a propensity to progress to acute myeloid leukemia. Impaired natural killer (NK) cell surveillance is a hallmark of MDS, yet the underlying molecular mechanisms remain poorly understood. This study aims to elucidate the mechanism by which HIF-1α regulates NK cell differentiation disorders and its impact on NK cell cytotoxicity in MDS. Flow cytometry was employed to compare HIF-1α expression and NK cell differentiation between wild-type and NUP98/HOXD13 (NHD13) mice. Our results demonstrated a significant increase in HIF-1α expression in the bone marrow and peripheral blood of MDS mice, accompanied by a notable decrease in immature NK cell subsets and activating receptors (NKG2D, NKp44, and DNAM-1). Overexpression of HIF-1α in human NK cells or pharmacological stabilization with CoCl2 inhibits the differentiation into mature NK cells, suppresses the expression of degranulation molecules such as Granzyme B, and impairs NK cell cytotoxicity. Western blot analysis indicated that HIF-1α regulates NK cell differentiation and function via the JAK1/STAT5/SOCS2 signaling pathway. Collectively, these findings suggest that the hypoxic microenvironment in MDS enhances HIF-1α expression, which subsequently impairs NK cell maturation and inhibits their cytotoxicity. Targeting HIF-1α may delay MDS progression by enhancing NK cell function via the JAK1/STAT5/SOCS2 signaling pathway.

Acquired drug resistance is a major cause of poor prognosis in multiple myeloma (MM). Bortezomib (BTZ), a first-line therapeutic agent, is highly effective in MM; however, resistance remains a significant clinical challenge. Our previous work implicated Solute Carrier Family 19 Member 1 (SLC19A1) in hypoxia and immune modulation, suggesting its potential role in malignant progression. Here, we found that SLC19A1 expression was elevated in MM patients, particularly in those with acquired resistance. Overexpression of SLC19A1 enhanced the proliferation and invasiveness of human myeloma cell lines but did not confer primary BTZ resistance. Using a continuous-BTZ-exposure model, we demonstrated that SLC19A1 overexpression mediated acquired resistance via chronic activation of the stimulator of interferon genes (STING) pathway. This sustained activation triggered the unfolded protein response, dysregulated the endoplasmic reticulum-mitochondrial axis, and induced mitochondrial DNA (mtDNA) release. Treatment with the SLC19A1 inhibitor sulfasalazine or the STING inhibitor H-151 reduced mtDNA release and restored BTZ sensitivity. These findings highlight SLC19A1 and STING signaling as potential therapeutic targets for overcoming acquired drug resistance in MM.

Background:Current prognostic stratification for acute myeloid leukemia (AML) patients primarily relies on international guidelines such as ELN 2022. However, these guidelines provide limited explicit guidance on how to comprehensively assess prognosis when patients harbor concurrent multiple gene mutations, potentially leading to inaccurate risk stratification. Methods:This retrospective cohort study enrolled 299 adult AML patients (median age: 53.5 years). Clinical features, mutation status of prognosis-related genes, complete remission (CR) rate after two induction courses, and overall survival (OS) were analyzed. Logistic regression and Cox proportional hazards models were employed. Results:In this study cohort, the incidence rates of NRAS and CEBPA single mutations were 15.38% (46/299) and 13.37% (40/299), respectively, while the NRAS and CEBPA co-mutation rate was 4.68% (14/299). Both univariate and multivariate logistic regression analyses demonstrated that CEBPA mutation (OR = 2.807, 95% CI: 1.244-6.333, P = 0.013) and NRAS mutation (OR = 4.028, 95% CI: 1.760-9.219, P = 0.001) were independent positive predictive factors for achieving complete remission after two treatment courses. Survival analysis indicated that neither NRAS single mutation (HR = 1.11, 95% CI: 0.60-2.04, P = 0.738) nor CEBPA single mutation (HR = 0.70, 95% CI: 0.36-1.34, P = 0.280) was significantly associated with overall survival. Notably, NRAS and CEBPA co-mutation was confirmed as an independent adverse prognostic factor, conferring a 3.15-fold increased risk of death (HR = 3.15, 95% CI: 1.08-9.21, P = 0.036) compared to patients without either mutation. Conclusion:The NRAS and CEBPA co-mutation defines a distinct molecular subtype with independently poor prognosis in AML. Routine NRAS mutation screening in patients with CEBPA-mutated AML is warranted to refine risk stratification, particularly for identifying this high-risk subgroup, which may benefit from more intensive or novel therapeutic approaches.

Objective:To conduct a comprehensive comparison of the efficacy, safety, and cost-effectiveness of denosumab versus zoledronic acid in patients with bone metastases from solid tumors and multiple myeloma. Methods:A systematic search of PubMed, Web of Science, Embase, and major Chinese databases was performed for studies published up to 30 September 2025. Eligible evidence included randomized controlled trials, cohort studies, and pharmacoeconomic analyses. Random-effects models were applied for quantitative synthesis. The certainty of evidence for key outcomes was assessed using the GRADE framework. Results:Twenty-one studies were included. Moderate-certainty evidence indicates that denosumab likely delays the time to first skeletal-related event (SRE) (HR = 0.85, 95% CI: 0.79-0.93) and time to first and subsequent SREs (HR = 0.86, 95% CI: 0.76-0.97) relative to zoledronic acid. Subgroup analyses demonstrated that this benefit is pronounced in solid tumors but not observed in multiple myeloma. For survival outcomes, moderate-certainty evidence suggests little to no difference in overall survival (HR = 0.97, P = 0.49) or progression-free survival (HR = 0.99, P = 0.86). Low-certainty evidence suggests that denosumab may reduce the risk of any adverse events (OR = 0.70, P = 0.04) and nephrotoxicity (OR = 0.65, P = 0.02). Pharmacoeconomic evaluations revealed marked geographic heterogeneity: denosumab was generally cost-effective in high-income settings with higher willingness-to-pay thresholds, whereas in resource-limited regions, zoledronic acid remained the more economically favorable option. Conclusion:Denosumab probably confers superior protection against SREs in patients with solid tumors and demonstrates a potentially improved renal safety profile compared with zoledronic acid. However, its cost-effectiveness varies substantially across healthcare systems and is strongly shaped by regional pricing structures and willingness-to-pay thresholds. Clinical adoption should therefore consider tumor biology, safety characteristics, and local economic capacity. Systematic review registration:https://www.crd.york.ac.uk/prospero/, identifier CRD420251020691.

Allogeneic stem cell transplantation (allo-HSCT) has recently been approved as standard therapy for transfusion-dependent thalassemia (TDT) but remains limited to the use of HLA-matched sibling donors (MSDs), due to a lack of large-scale prospective studies evaluating the use of grafts from alternative donors. Here, we report the results of a non-randomised, interventional, phase 4 clinical trial evaluating allo-HSCT from alternative donors for the treatment of TDT. A total of 823 patients with TDT were transplanted with grafts from MSDs (n = 331) or alternative donors, including matched unrelated donors (MUDs; n = 352) and haploidentical related donors (Haplos; n = 140). Conditioning was with busulfan, cyclophosphamide, fludarabine and anti-thymocyte globulin. Graft-versus-host disease (GvHD) prophylaxis was cyclosporine, methotrexate (MTX) and mycophenolate mofetil (MMF) for recipients of MSDs and tacrolimus, MTX, MMF for others. The primary endpoints were 2-year overall survival (OS) and event-free survival (EFS). Two-year OS for MSDs, MUDs, Haplos was 97.2% (95% CI, 95.4-99.0), 93.1% (90.5-95.9) and 95.4% (91.9-99.1); EFS was 97.2% (95.4-99.0), 92.9% (90.1-95.7) and 94.7% (90.9-98.6); GvHD-free, relapse-free survival (GRFS) was 91.4% (88.4-94.6), 77.0% (72.6-82.7) and 75.6% (68.5-83.4) respectively. Two-year OS and EFS for MUDs were lower than those for MSDs (both P < 0.05) and were not significantly different with those for Haplos (both P > 0.05). Transplant-related mortality was 4.4% (3.0-5.9) and graft failure rate was 0.5%. The incidence of grades 2-4 acute GvHD and moderate-severe chronic GvHD from alternative donors were higher than those from MSDs (28.9% [24.7-33.2] vs 7.5% [4.9-10.7], P < 0.001; 12.3% [9.2-15.7] vs 5.0% [2.9-7.9], P < 0.01). In summary, these findings may help expand the donor pool for patients with TDT lacking MSDs (ClinicalTrials.gov: NCT04009525).

Multiple myeloma (MM), the second most common haematological malignancy, remains incurable to date. Based on Global Burden of Disease 2021, global trends in MM incidence, mortality and disability-adjusted life-years (DALYs) were analysed and visualized. Estimated annual percentage changes (EAPCs) quantified trends and future disease burden (2022-2050) were forecasted using autoregressive integrated moving average time-series models. From 1990 to 2021, the global burden of MM incidence showed a slight increase, primarily affecting ageing populations and high/high-middle sociodemographic index (SDI) regions. This rise was more significant in males and notably in middle SDI regions (including East Asia, Central Asia and Western Sub-Saharan Africa). Mortality trends exhibited minimal overall growth; female age-standardized death rates (ASDRs) decreased, especially in high SDI regions. Across 204 countries and 21 SDI regions, MM ASDRs correlated positively with SDI, while EAPCs correlated negatively with Human Development Index (HDI), age-standardized incidence rates (ASIRs) and ASDRs. Projections indicate rising ASIRs for both sexes and increasing ASDRs and age-standardized DALY rates among males through 2050. Additionally, population-attributable fractions of MM deaths and DALYs due to high body mass index showed upward trends across all SDI regions from 1990 to 2021. Over three decades, global MM incidence has moderately increased, most affecting ageing populations and high/high-middle SDI regions. Notably, global mortality and DALY rates have declined since 2000, especially in females and high SDI regions. Initiatively, our study identified a significant negative correlation between the HDIs and EAPCs of MM incidence and mortality and takes SDI as the core external predictor to project the global MM disease burden up to 2050.

ObjectiveThis study evaluated the effectiveness of Kangfuxin liquid against autologous stem cell transplantation toxicity in patients with multiple myeloma.MethodsThis single-center retrospective study involved 82 participants, divided into the simple oral cryotherapy group (control group), which included 43 patients with multiple myeloma who underwent autologous hematopoietic stem cell transplantation before May 2023, and the Kangfuxin liquid + oral cryotherapy group (experimental group), which included 39 patients with multiple myeloma, who underwent autologous hematopoietic stem cell transplantation after June 2023. Statistical analysis indicators included infection, gastrointestinal toxic side effects, efficacy evaluation, and prognostic analysis.ResultsCompared with the control group, the experimental group had a higher mean age (p = 0.003), fewer reinfused stem cells (p < 0.001), and a longer neutrophil and platelet engraftment time (p = 0.001 and p < 0.001). The experimental group had lower auxiliary treatment costs (p < 0.0001), and significantly lower infection incidence (p = 0.001) and mucositis and diarrhea grading (p = 0.046), indicating a protective effect. There were no additional adverse reactions, and the treatment efficacy for the patients’ primary diseases remained unaffected.ConclusionKangfuxin liquid significantly reduces mucosal damage, shortens hospitalization, lowers medical costs, and does not compromise the therapeutic efficacy of autologous transplantation for multiple myeloma, providing evidence for clinical treatment.

Background Conditioning regimens are crucial in allogeneic hematopoietic stem cell transplantation (allo-HSCT), especially for older patients (≥7 years) with transfusion-dependent thalassemia (TDT) recieving haplo indentical transplantation (HID). The development of low-toxicity conditioning yet myeloablative regimens is essential to address the dual challenges of high graft rejection rates and transplant-related mortality. Objective This study aimed to evaluate the efficacy and safety of the F-BMT conditionig regimen in improving allo-HSCT outcomes for TDT patients, especially for older patients with HID transplantation . Methods This prospective, multicenter clinical trial was conducted at 923rd Hospital of the Joint Logistics Support Force, the First Affiliated Hospital of Guilin Medical University, and the Eighth Affiliated Hospital of Southern Medical University.Patients with TDT aged 3–25 years were enrolled. The F-BMT regimen included fludarabine 30 mg/m² (days –7 to –2), busulfan 130 mg/m² (day –7), thiotepa 250 mg/m² (day –5), melphalan 100 mg/m² (day –3). For graft versus host disease (GVHD) prentation, porcine anti-human lymphocyte immunoglobulin (p-ALG) (25 mg/kg) or antithymocyte globulin (r-ATG) (2.5 mg/kg ) on days –1, cyclophosphamide 25 mg/kg (days +3 and +4)，methotrexate 5 mg/m² (day +5), cyclosporine (initiated on day +5, continued for 12 months). For HID donors, additional agents were administered: p-ALG (25 mg/kg ) or r-ATG (2 mg/kg) on day day +5, ruxolitinib (days +5 to +28). The primary endpoint was 1-year thalassemia-free survival (TFS). (ChiCTR2300077054) Results From June 2023 to May 2025, 91 patients were enrolled. The median age was 10.0 years (range: 4-19 years), among them 76 patients aged ≥7y, and 63 patients with HID donors. With a median follow-up duration of 12 months (range: 3-25 months). 1-year TFS was 94.24%, 1-year overall survival (OS) was 96.44%.Two patients (2.2%) died from severe pneumonia or sepsis. The remaining 89 patients achieved both neutrophil and platelet engraftment within 28 days post-transplantation, with full donor chimerism. One patient experienced secondary graft failure due to infection, and one patient had primary graft failure. Both of these patients underwent secondary transplantation with successful engraftment.The engraftment rate by day +28 post-transplantation was 97.78%. The mean time to neutrophil engraftment was 13.7 ± 1.5 days, and the mean time to platelet engraftment was 13.1 ± 3.9 days. By day +100 post-transplantation, the cumulative incidence of grade II-IV aGVHD was 7.1%, with only 4.4% (n=4) of patients developing grade III-IV aGVHD. Grade 1-2 hemorrhagic cystitis (HC) occurred in 3.3% (n=3) of patients. Viral reactivation was observed in 26% (n=24) of patients, including Cytomegalovirus (CMV) reactivation in 18 patients and Epstein-Barr virus (EBV) reactivation in 8 patients; 2 of these patients had concurrent CMV and EBV reactivation.Infections occurred in 12% (n=11) of patients within the first 3 months post-transplantation, including bacteremia in 11% (n=10). One patient developed posterior reversible encephalopathy syndrome (PRES), one had an invasive fungal infection, and two patients developed veno-occlusive disease (VOD). Post-transplant lymphoproliferative disorder (PTLD) was diagnosed in one patient and was cured after Rituximab injection.. Chronic graft-versus-host disease (cGVHD) occurred in 8.9% (6 cases) of evaluable patients, involving the pulmonary and hepatic systems, with all cases rated as moderate; all cases were cured with appropriate therapy. No cases of thrombotic microangiopathy (TMA) were observed. Conclusion This study demonstrates that the F-BMT conditioning regimen followed by HSCT represents a low-toxicity protocol with significant efficacy and safety in TDT patients, even in older patients with HID donors.

Introduction: Carfilzomib (CFZ) and pomalidomide maintain clinical efficacy in relapsed/refractory multiple myeloma (RRMM). The phase 2 SELECT trial demonstrated ​​once-weekly KPd (CFZ 56 mg/m²)​​ as an effective and well-tolerated regimen for lenalidomide-refractory RRMM (Perrot, Aurore et al. Leukemia & lymphoma 2024), distinct from historical ​​twice-weekly KPd (CFZ 27-36 mg/m²)​​ data. ​​Prospective real-world evidence for once-weekly K56Pd in first-relapse MM remains limited.​​ We therefore conducted a multicenter prospective study evaluating ​​once-weekly K56Pd​​ in this population to generate critical real-world evidence. Methods: Eligible participants were adults aged ≥18 years with RRMM，and Eastern Cooperative Oncology Group (ECOG) performance status was 0–2, measurable disease per International Myeloma Working Group criteria, and documented disease progression following exactly one prior line of systemic therapy. All enrolled patients received K56Pd treatment. Carfilzomib was administered intravenously at 20 mg/m² on day 1 and 27 mg/m² on day 2 of cycle 1, then increased to 56 mg/m² on days 8 and 15 (cycle 1) and subsequently on days 1, 8 and 15 of each following cycle; pomalidomide, 4 mg orally once daily on days 1-21; dexamethasone, 40 mg orally on days 1, 8, 15, and 22. The primary efficacy endpoint was the proportion of patients achieving ≥very good partial response (VGPR).secondary endpoints included overall response rate (ORR), complete response (CR) rate,progression free survival (PFS), overall survival (OS), and safety.The study was approved by the Ethics Committee of the First Affiliated Hospital of Guilin Medical University (Approval No.2024IITLL-09) Results: Herein, we reported the preliminary results. Between Jan 24, 2024, and Apr 17, 2025, 31 patients were enrolled. The median age at the start of weekly K56Pd regimen was 69 years old (range, 39-76) and 48.4% were male. Among these eligible patients, 12 (38.7%) of them had received previous autologous hematopoietic stem cell transplantation. Prior therapies included bortezomib (19.4% refractory), lenalidomide (90.3% refractory), and anti-CD38 antibodies (3.2% refractory); 6 (19.4%) were dual-refractory to bortezomib/lenalidomide, and 1 (3.2%) triple-refractory (bortezomib/lenalidomide/anti-CD38). There were 16 patients with high-risk features including ISS stage III (51.6%), extramedullary disease (25.8%), and cytogenetic abnormalities: t(4;14) (12.9%), 1q21 amplification (64.5%), and del(17p) (6.45%). The median duration of treatment was 15.0 months. All 31 patients completed the initial 2 cycles of treatment, the rate of ≥VGPR was 22.6% (ORR: 90.3%, CR: 19.4%). 22 patients completed 4 cycles of treatment, the rate of ≥VGPR was 63.6% (ORR: 88.2%, CR: 36.4%, sCR: 9.1%). 17 patients completed 6 cycles of treatment, the rate of ≥VGPR was 82.4% (ORR: 88.2%, CR: 35.3%, sCR: 17.6%). After a median follow-up of 8.4 months, the median PFS was 17.0 months (95%CI, NE, NE) and the median OS was not reached. The most common grade 3 treatment related adverse events (TRAE) included anemia (n=3, 9.68%), leukopenia (n=3, 9.68%), infection (n=2, 6.45%), hypertension (n=2, 6.45%) and thrombopenia (n=2, 6.45%). No grade 4 adverse events occurred; no patients died due to TRAE. Conclusion: The weekly K56Pd regimen demonstrated meaningful clinical benefits and manageable safety in patients with MM at first relapse in real-world settings.

BackgroundBoth venetoclax plus a hypomethylating agent (VEN/HMA) and cytarabine, aclarubicin, and granulocyte colony-stimulating factor (CAG) are low-intensity regimens for older patients with acute myeloid leukemia (AML) that show good efficacy and safety. It is unknown how VEN/HMA compares with the CAG regimen for the treatment of newly diagnosed AML.MethodsThe outcomes of patients with newly diagnosed AML treated with VEN/HMA were compared with those of patients treated with a CAG-based regimen. Propensity score matching between these two cohorts at a 1:1 ratio was performed according to age at diagnosis, sex, Eastern Cooperative Oncology Group performance status, state of fitness, and European LeukemiaNet (ELN) 2022 risk stratification to minimize bias.ResultsA total of 84 of 96 patients in the VEN/HMA cohort were matched with 84 of 147 patients in the CAG cohort. VEN/HMA resulted in a better response than the CAG-based regimens, as indicated by a higher composite complete remission (CRc) rate (82.1% vs. 60.7%; p = .002) and minimal residual disease negativity rate (88.2% vs. 68.2%; p = .009). In patients with an ELN adverse risk, VEN/HMA was associated with a higher CRc rate compared to CAG (80.5% vs. 58.3%; p = .006). VEN/HMA was associated with longer event-free survival (EFS) (median EFS, not reached vs. 4.5 months; p = .0004), whereas overall survival (OS) was comparable between the two cohorts (median OS, not reached vs. 18 months; p = .078).ConclusionsThe VEN/HMA regimen may result in a better response than CAG-based treatment in older patients with newly diagnosed AML. Patients newly diagnosed with acute myeloid leukemia responded better to venetoclax plus a hypomethylating agent than to cytarabine, aclarubicin, and granulocyte colony-stimulating factor-based treatment regimens.

BACKGROUND:Patients with Hematological Malignancies (HM) are at a high risk of mortality from Coronavirus disease 2019 (COVID-19). The available antivirals were different between China and other countries. In China, azvudine was obtained for emergency use to treat adult COVID-19 patients with moderate symptoms in July 2022. While nirmatrelvir-ritonavir was well-known and used in many countries. The purpose of the present study was to assess whether there was any difference in the efficacy and safety of the two drugs. METHODS:This study was a prospective observational study of patients with HM who developed COVID-19. Patients were divided into three treatment groups: nirmatrelvir-ritonavir, azvudine, and observation. Treatment outcomes, first nucleic acid test negative time, hospitalization time, and the conversion rate of mild or moderate disease to severe disease were recorded. RESULTS:First nucleic acid test negative time (23.5 days vs. 34 days, p = 0.015), hospitalization time (p = 0.015), and conversion rate (31.8 % vs. 8 %, p = 0.046) were statistically different between the nirmatrelvir-ritonavir and observation groups. First nucleic acid test negative time (20 days vs. 34 days, p = 0.009) and hospitalization time (p = 0.026) were statistically different between the azvudine and observation groups. ECOG score and liver disease were significantly associated with the conversion rate from mild or moderate disease to severe disease using multivariate analysis (p < 0.05). CONCLUSIONS:The authors found no significant differences existed in outcome measures between patients with HM and COVID-19 who were treated with nirmatrelvir-ritonavir or azvudine.

Abstract: Introduction: Immune thrombocytopenia (ITP) is a complex autoimmune disease characterized by abnormally low blood platelet count, resulting in an increased risk of bleeding. Beceltinib, an oral irreversible covalent inhibitor of Bruton's tyrosine kinase, has shown potential as a therapeutic approach for ITP. This study aimed to evaluate the efficacy and safety of Beceltinib in adult patients with persistent or chronic ITP. Methods: In this multicenter, randomized, open-label, phase 1/2 study, adult patients with primary ITP who had previously failed standard therapy or could not tolerate it were enrolled. Patients were randomly assigned to receive either 50mg, 75mg, or 100mg of Beceltinib twice daily for 24 weeks. The primary endpoint was the proportion of patients achieving platelet counts of ≥50×109/L for at least two consecutive weeks during the treatment period. The secondary efficacy end points were sustained platelet response which defined as the proportion of patients with at least 4 platelet counts≥50×109/L during the last 6 visits within 24 weeks without rescue medication use. Safety monitoring, including adverse events, physical examinations, and bleeding risk assessments, was conducted throughout the trial. Pharmacokinetics and pharmacodynamics of Beceltinib were also explored. Results: A total of 32 patients were enrolled in the study, and 13 patients (40.6%) achieved the primary endpoint which is two consecutive platelet counts of at least 50 x 109/L during 24-week treatment period. Out of the responders, 11 patients (84.6%) demonstrated a sustained response, indicating that majority of the patients who positively responded to Beceltinib exhibited continued efficacy. The median cumulative response duration was 22 weeks (interquartile range, 12 to 31). The median time to the first platelet counts of at least≥50×109/L was 3 week (range, 1 to 9). Patients who had responded to glucocorticoids in the past showed better primary platelet response (61.5%, 8 of 13) and sustained platelet response (53.8%, 7 of 13). Dose adjustments were made in some patients, and the effective rate varied across different dose levels. The incidence of adverse reactions was 43.8%, with most being mild (grades 1 or 2). The study demonstrated that Beceltinib was generally well-tolerated by ITP patients. Conclusion: This study suggests that Beceltinib may have potential efficacy and safety for the second-line treatment of ITP. The findings provide new treatment options for clinical practice. Further studies are needed to validate these results and assess the long-term effects of Beceltinib in ITP patients.

Background: “7+3” induction is the standard regimen in newly diagnosed young patients (pts) with acute myeloid leukemia (AML) fit for intensive chemotherapy with 60-80% complete remission rate. However, middle aged and elderly pts may experience more severe complications during induction therapy and overall survival is shorter than that of younger pts. Recently, venetoclax with azacitadine as induction therapy was approved as the first line therapy for pts with aged more than 75 years or unfit pts with composite complete remission (CRc) of 60-70%. We hypothesize that venetoclax with azacitadine as induction therapy in fit middle aged and elderly pts may have similar CRc rate and less complications. This study aims to evaluate the safety and efficacy of venetoclax plus azacitadine as induction therapy in fit middle aged and elderly newly diagnosed AML pts. Methods: This is an interim analysis of an ongoing phase 2 clinical trial (NCT05471700) of a planned 40 untreated AML pts aged 45-65 who were fit for intensive chemotherapy according to Ferrara Criteria. In cycle 1, pts received azacitadine 75mg/m2/day on d1-7 and venetoclax escalated from 100mg to 200mg to 400mg until 28-day cycle was finished. For pts with FLT3-ITD positive, sorafenib was optional administered at a dose of 400mg twice daily. Bone marrow assessments were performed on d28. Pts who achieved CRc (defined as complete remission[CR] and CR with incomplete hematologic recovery[CRi]) with intermediate or adverse risk groups received 1 or 2 cycles of consolidation with venetoclax plus azacitadine or center-specific cytarabine-based consolidation. Allogeneic stem cell transplantation (HSCT) was performed if a donor was available. Pts in favorable risk gruop received 3 to 4 cycles of center-specific intermediate or high dose cytarabine-base consolidation. Non-responders or pts who achieved partial remission received 1 more cycle of venetoclax plus azacitadine. Who could not get CRc after 2 cycles of induction would be withdrawn from the study. The primary objective is to determine the CRc rate. The secondary objective is safety, MRD negative rate, duration of remission (DOR), the rate of allo-HSCT, event free survival (EFS), and overall survival (OS). The endpoint is to show that venetoclax plus azacitadine is not inferior to “3+7” induction in fit pts with newly diagnosed AML aged 45-65. Results: From 10/9/2022 to 6/30/2023, a total of 32 pts was enrolled to this study, comprising 18 males and 14 females. There were 27 (84%) pts with de novo AML, 2(6%) pts were secondary AML, 3 pts (9.4%) were therapy-related AML. Median age was 58 years (range, 45-64 years). There were 2(6%), 14(44%) and 16(50%) pts were in the favorable, intermediate and adverse risk group, respectively. The baseline patient characteristics are summarized in Table 1. Outcome data were updated as of June 30, 2023, for a median follow-up of 2.2(0.2-8.8) months. Among 27 evaluable pts, 21(77.8%) achieved CRc with 11(40.8%) in CR and 10(37.0%) in CRi, 2(7.4%) achieved PR in cycle1, while 23(85.2%) achieved CRc with 14(51.9%) in CR and 9(33.3%) in CRi, 4(14.8%) got induction failure after 2 cycles(Figure 1). A total of 16 (61.5%) pts got MRD negative among the pts with CRc after cycle1, and 17 (65.4%) after cycle2. CRc rate after 2 cycles in ELN2017 favorable, intermediate, adverse risk group was 100%, 83.3% and 85.0%, respectively, and MRD negative rate was 100%, 88.9% and 55.6%, respectively. The regimen was well tolerated. No mortality occurred during induction therapy. The most common non-hematological grade 3/4 AE were febrile neutropenia (n=13, 40.6%)，followed by pneumonia (n=3, 9.4%).Sepsis occurred in 1 (3.1%) pt. With a median follow-up of 2.2(0.2-8.8) months, the median remission duration, EFS and OS have not been reached. Conclusions: Preliminary results indicate that venetoclax plus azacitadine as an induction regimen for fit middle aged and elderly pts with newly diagnosed AML is promising with high CRc and low toxicity. Recruitment of adults with newly diagnosed aged 45-65 AML pts for this trial is ongoing.

Abstract Background: Venetoclax(VEN) combination with hypomethylating agent(HMA) are lower-intensity regimens with safety which are widely used for older patients with newly diagnosed acute myeloid leukemia (AML). On the other hand, regimen of cytarabine, aclarubicin and G-CSF (CAG) with or without HMA is also of low-intensity usually applied to older AML patients. The comparison of outcomes of these two regimens has not been reported. In this study, we performed a multicenter, retrospective propensity score-matched study to compare the therapeutic responses and survival outcomes of newly diagnosed AML patients with induction of HMA-VEN to those with CAG based treatment. Methods: Newly diagnosed AML patients treated either VEN/HMA or CAG with or without HMA between January 2013 and April 2023 were compared. Age at diagnosis, sex, ECOG performance status, state of fitness for intensive chemotherapy according to Ferrara criteria and ELN2017 risk group were used to construct the propensity score using logistic regression. Propensity score matching was performed in a 1:1 ratio with a calliper value of 0.02. The treatment response, relapse rate, duration of remission, overall survival (OS) were compared between the two groups. Results: A total of 98 out of 109 newly diagnosed patients treated with VEN/HMA were matched to 98 out of 159 newly diagnosed patients treated with CAG based therapy. The patients in VEN/HMA cohort were treated between February 25, 2021 and April 30, 2023. The CAG based treatment recipients were treated from January 25, 2013 to November 12, 2021. The CAG based treatment cohort which was termed as “CAG cohort” below matched closely with the VEN/HMA cohort in terms of baseline characteristics and propensity scores (Table1). The median age was 62 years (range, 52-67) in VEN/HMA cohort and 63 years (range,52-68) in CAG cohort, and the median follow-up period was 6.3 months (range,3.2-14.0) in VEN/HMA cohort and 12 months (range,3.8-28.3) in CAG cohort. Patients treated with VEN/HMA achieved a significantly higher rate of CRc (82.4% vs 60.6%, P=0.002) compared to CAG cohort, with 36.5% in CR, 45.9% in CRi in VEN/HMA cohort and 30.3% in CR, 30.3% in CRi in CAG cohort. There was no statistic difference of the CRc rate between CAG versus CAG plus HMA(35.7%，n=14 vs 60.5%,n=76, p=0.085). CRc in the VEN/HMA and CAG cohort were 100% vs 85.7(p=0.483), 75.9% vs 46.9%(p=0.021), 64.3% vs 45.2%(p=0.079) in the ELN2017 favorable, intermediate and adverse risk group, respectively. The MRD-negative remission rate was higher in VEN/HMA cohort compared to CAG cohort (85.5% vs 61.2%, p= 0.003). The MRD-negative remission rate in the VEN/HMA and CAG cohort were 91.6% vs 80.0%(p=0.571), 88.0% vs 66.6%(p=0.188), 83.9% vs 45%(p=0.003) in the ELN2017 favorable, intermediate and adverse risk group, respectively(Table2). Responses of patients with different mutations were analyzed and ASXL1 predicted higher CRc rate with VEN/HMA treatment compared to CAG based treatment (92.3% vs. 40%, p= 0.019). The median OS was not reached in VEN/HMA cohort and 18 months in CAG cohort(p=0.16). Patients who achieved CRc had longer survival than those without CRc (not reached vs 6.4m, p<0.001). Patients who got MRD negative remission had better survival than those only with MRD positive remission (not reached vs 11.8m, p=0.0002). Patients who underwent allogeneic HSCT had longer survival than those didn't receive transplantation (not reached vs 12.3m, p<0.001). Conclusions: With propensity score-matched analysis, our data show that VEN/HMA demonstrates better treatment response than CAG regimen in patients with newly diagnosed AML. The survival outcome benefits from MRD negative response and allogeneic HSCT. Disclosures No relevant conflicts of interest to declare.

Chronic myeloid leukemia (CML) is a chronic disease with treatment-free remission (TFR) increasingly regarded as a feasible goal of treatment. However, various factors may influence adherence to international guidelines for CML management. This study aimed to compare the reporting of care between patients with CML and their treating doctors. Parallel patient and physician online surveys were conducted between September 22, 2021, and March 15, 2022, which focused on the perceptions of 1882 adult patients with CML and 305 physicians regarding tyrosine kinase inhibitor (TKI) treatment options, monitoring and toxicities, TFR, and challenges faced. Among the enrolled patients, 69.9

BackgroundChronic myeloid leukemia (CML) is a chronic disease with treatment-free remission (TFR) increasingly regarded as a feasible goal of treatment. The optimal outcome achieved in CML requires both prolonged adherence to oral tyrosine kinase inhibitor (TKI) therapy by patients and careful monitoring of treatment responses by their physicians. Various factors would impact doctors following international guidelines for CML management in real-word, however, very few studies has investigated possible discrepancies between patient- and physician-reporting in the CML setting. Objective To compare the reporting of care between CML patients and their treating doctors, and to explore the underlying causes for both physicians and patients non-adherence. MethodsParallel patient and physician online surveys were conducted between September 22, 2021 and March 15, 2022, using the WeChat-based survey program Wenjuanxing. Descriptive analysis of the results mainly focused on CML adults patients and physicians treating CML regarding TKI treatment options, monitoring and toxicities, TFR, and facing challenges. ResultsA total of 1882 patients and 305 physicians completed the survey. Among the enrolled patients, 69.9% received imatinib as first-line therapy, of them 47.0% switched to other TKIs due to imatinib resistance/intolerance (58.5%), exploration on more potent TKI to achieve TFR (13.1%), and treating physicians’ recommendation (15.8%). 91.8% of the physicians believed BCR-ABL1 level should be assessed every 3 months, however, only 42.7% patient respondents committed to 3-monthly testing and 17.8% strictly followed their treating physicians’ recommendation. Half of the patients (49.9%) aimed at TFR, however, just 45.2% physicians considered TFR as one of the three major treatment objectives, obstacles to achieve TFR mainly attributed to their patients. Fatigue and anemia were the key negative impactors for patients who were significantly associated with higher incidence of mental disorders, whilst physicians paid more attention to platelet and neutrophil count. Incidence of moderate to severe anxiety or depression is 12.0% and 20.8%, respectively; but only 41.3% of patients needed support from their doctors, and 53.7% physicians provided their patients with additional support. 13.7% patients had delayed follow-up visit and molecular monitoring, 7.4% patients discontinued TKI or reduced TKI dose due to economic difficulties (69.2%), which resulted in 10.2% patients suffering from disease progression amid the COVID-19 pandemic. 42.3% patients were vaccinated for SARS-CoV-2, another 57.7% patients against vaccine because of safety concern. Cost is the major impactor for treatment choices, molecular monitoring, treatment objective, mental health, and even the treatment under the pandemic, which were fully recognized by both the patients and physicians. ConclusionsPhysicians who joined our survey had low awareness on patients’ fatigue and anemia. Mental disorders existed in a significant proportion of patients, whereas less concerned by both patients and physicians. Cost is the major impactor for physician and patient adherence to current clinical practice guidelines, especially under current COVID-19 pandemic in China.

Background Individuals with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs) are at risk of developing venous thromboembolism (VTE), a serious complication. There is no established clinical model for predicting VTE in the Chinese population. We develop a new risk assessment model (RAM) for IMiD-associated VTE in Chinese MM patients. Methods We retrospectively selected 1334 consecutive MM patients receiving IMiDs from 16 medical centers in China and classified them randomly into the derivation and validation cohorts. A multivariate Cox regression model was used for analysis. Results The overall incidence of IMiD-related VTE in Chinese MM patients was 6.1%. Independent predictive factors of VTE (diabetes, ECOG performance status, erythropoietin-stimulating agent use, dexamethasone use, and VTE history or family history of thrombosis) were identified and merged to develop the RAM. The model identified approximately 30% of the patients in each cohort at high risk for VTE. The hazard ratios (HRs) were 6.08 (P < 0.001) and 6.23 (P < 0.001) for the high-risk subcohort and the low-risk subcohort, respectively, within both the derivation and validation cohorts. The RAM achieved satisfactory discrimination with a C statistic of 0.64. The stratification approach of the IMWG guidelines yielded respective HRs of 1.77 (P = 0.053) and 1.81 (P = 0.063). The stratification approach of the SAVED score resulted in HRs of 3.23 (P = 0.248) and 1.65 (P = 0.622), respectively. The IMWG guideline and the SAVED score-based method yielded C statistics of 0.58 and 0.51, respectively. Conclusions The new RAM outperformed the IMWG guidelines and the SAVED score and could potentially guide the VTE prophylaxis strategy for Chinese MM patients.

\ Autophagy has an important role in the pathogenesis of plasma cell development and multiple myeloma (MM); however, the prognostic role of autophagy-related genes (ARGs) in MM remains undefined. In the present study, the expression profiles of 234 ARGs were obtained from a Gene Expression Omnibus dataset (accession GSE24080), which contains 559 samples of patients with MM analyzed with 54,675 probes. Univariate Cox regression analysis identified 55 ARGs that were significantly associated with event-free survival of MM. Furthermore, a risk score with 16 survival-associated ARGs was developed using multivariate Cox regression analysis, including ATIC, BNIP3L, CALCOCO2, DNAJB1, DNAJB9, EIF4EBP1, EVA1A, FKBP1B, FOXO1, FOXO3, GABARAP, HIF1A, NCKAP1, PRKAR1A and SUPT20H, was constructed. Using this prognostic signature, patients with MM could be separated into high- and low-risk groups with distinct clinical outcomes. The area under the curve values for the receiver operating characteristic curves were 0.740, 0.741 and 0.712 for 3, 5 and 10 years prognosis predictions, respectively. Notably, the prognostic role of this risk score could be validated with another four independent cohorts (accessions: GSE57317, GSE4581, GSE4452 and GSE4204). In conclusion, ARGs may serve vital roles in the progression of MM, and the ARGs-based prognostic model may provide novel ideas for clinical applications in MM.

Recently, it is found that level of lactate dehydrogenase (LDH) is an important prognostic factor in patients with multiple myeloma (MM). It is reported that in patients with MM, elevation of LDH i...