NPM1-mutated acute myeloid leukemia (AML) is a distinct entity with specific biological and clinicopathological features. Prognosis varies depending on the associated mutations and clinical characteristics. This study evaluated the prognostic factors of NPM1-mutated AML in patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). We enrolled 139 patients with NPM1-mutated AML who underwent allo-HSCT. The median age at allo-HSCT was 47 years with a median follow-up of 1,134 days. The 3-year cumulative incidence of relapse (CIR), leukemia-free survival (LFS), and overall survival (OS) rates were 15.1%, 78.4%, and 78.0%, respectively. FLT3-ITD mutations showed higher CIR (22.6% vs 5.3%, P = 0.006), lower LFS (70.9% vs 88.1%, P = 0.019), and reduced OS (70.8% vs 87.5%, P = 0.036). FLT3-ITD and DTA mutations indicated adverse prognosis, while IDH1/2 mutations showed improved outcomes. Matched sibling donor (MSD) allo-HSCT patients had higher CIR and lower LFS and OS than unrelated donor (URD) or haploidentical-related donor (HRD) recipients. Pre-HSCT MRD status affected the outcomes, with MRD+ and nCR patients showing worse outcomes. Multivariable analysis identified FLT3-ITD, MSD, and pre-MRD status as significant predictors. In conclusion, FLT3-ITD and DTA mutations are associated with an adverse prognosis, whereas HRD or URD transplants may offer better outcomes than MSD allo-HSCT.

Diffuse large B-cell lymphoma (DLBCL) exhibits 30–40

The prognostic role of Epstein-Barr virus (EBV) DNA in aggressive angioimmunoblastic T-cell lymphoma (AITL) remains unclear. This study aimed to investigate the prognostic significance of whole blood EBV DNA at diagnosis in AITL patients, establish an optimal prognostic cutoff, and develop a novel prognostic index incorporating this viral biomarker. This multicenter retrospective study included 323 newly diagnosed AITL patients. The optimal cutoff of EBV DNA was determined using maximally selected rank statistics. Independent prognostic factors identified by multivariate Cox regression were used to construct a novel prognostic index (AITL prognostic index [API]), which was internally validated and compared with existing models. At diagnosis, 241 (74.6

Castleman disease (CD) represents a heterogeneous group of hematologic disorders characterized by distinct histopathological features. While CD is regarded as a pre-lymphomatous condition, its reactive or neoplastic nature is still a matter of controversy. Although rare, lymphoma has been reported in patients with CD, most commonly B-cell lymphomas. Here, we present a case of a 69-year-old man initially diagnosed with CD who subsequently developed angioimmunoblastic T-cell lymphoma (AITL) during treatment. To elucidate the potential biological relationship between these two disease entities, we performed whole-exome sequencing to compare genomic alterations between the two disease states. Additionally, we provide a concise review of published cases documenting lymphoma occurring after or coexisting with CD, summarizing patients’ characteristics and the various treatment strategies employed thus far.

ABSTRACT In recent years, daratumumab has been increasingly applied in the treatment of systemic light‐chain (AL) amyloidosis, significantly improving the prognosis of patients. Currently, the internationally recognized daratumumab treatment regimen comes from the ANDROMEDA trial. Given the low tumor burden and poor tolerance of patients with amyloidosis, in this study, we modified the ANDROMEDA‐based protocol by administering daratumumab at half the original frequency. We enrolled 48 patients with AL amyloidosis who received low‐frequency daratumumab in multiple hospitals from July 2021 to May 2024 (ChiCTR2100049253). Among these patients, 38 were newly diagnosed and 10 were relapsed and refractory patients. At 3 months, the percentage of newly diagnosed patients with hematologic response≥very good partial response (VGPR) was 75.8%, including 36.4% complete response (CR) and 39.4% VGPR, with an overall response rate (ORR) of 90.9%. The CR, VGPR and ORR rates of relapsed and refractory patients at 3 months were 40.0%, 20.0% and 90.0%, respectively. By 6 months, ≥VGPR was achieved by 86.7% of newly diagnosed patients, while CR, VGPR, and ORR in relapsed and refractory patients were 44.4%, 22.2%, and 77.8%. The 6‐month cardiac and renal response rates were 61.9% and 46.2% in newly diagnosed patients, 20.0% and 50.0% in relapsed and refractory patients, respectively. The median follow‐up time was 26.0 months. The 1‐year and 2‐year OS rates were both 89.5% for newly diagnosed patients, and 90.0% for relapsed and refractory patients. Of the 48 patients, 33 (68.8%) received maintenance therapy and 15 (31.3%) did not. The 1‐year and 2‐year OS rates were both 100.0% for patients receiving maintenance, and 66.7% for patients without maintenance. Considering the safety endpoints, 86.8% of newly diagnosed patients experienced at least one adverse event (AE). In conclusion, the low‐frequency daratumumab regimen can be considered as an effective, safe and feasible treatment strategy for AL amyloidosis.

To investigate the clinical characteristics, neurological manifestations, and survival outcomes of patients with pathologically confirmed spinal lymphoma and to identify factors associated with prognosis. We retrospectively reviewed consecutive patients with pathologically confirmed spinal lymphoma treated at the First Affiliated Hospital, Zhejiang University School of Medicine, between Jan 2012 and Dec 2025. Clinical characteristics, treatment patterns, and survival outcomes were analyzed. Overall survival (OS) was estimated using the Kaplan–Meier method, and prognostic factors were evaluated using Cox proportional hazards models. Sixty-three patients were included. The median age was 63 years, and 90.5

Sequential allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a critical approach to enhance the efficacy of chimeric antigen receptor T cell (CAR-T) therapy for relapsed/refractory acute lymphoblastic leukemia (R/R ALL). The long-term survival rates following allo-HSCT after CAR-T cell therapy remain controversial. We previously reported the results of 122 patients with R/R B-ALL who achieved minimal residual disease negative (MRD-) complete remission (CR) after anti-CD19 CAR-T, including 67 patients without subsequent transplantation (non-transplant group) and 55 patients with subsequent haplo-HSCT (transplant group). Here, we present the extended follow-up of this cohort, with a median of 72.9 months. Compared with the non-transplant group, transplantation recipients had a higher 5-year LFS (50.5% vs. 25.7%; p < 0.001) and OS (53.5% vs. 25.6%; p < 0.001). Multivariable analysis identified MRD positivity at transplantation as an independent factor associated with worse LFS, OS, and a higher cumulative incidence rate of relapse (CIR). MRD-negative patients before transplant (MRD- group) had a lower 5-year CIR compared to MRD-positive patients (MRD+ group) (20.8% vs. 50.0%; p = 0.014). The 5-year LFS rates in the MRD+ and MRD- groups were 26.7% and 59.4%, respectively (p = 0.003). The 5-year OS of the MRD- group was higher than that of the MRD+ group (62.0% vs. 30.5%; p = 0.006). For patients who achieve CR after CAR-T therapy, haplo-HSCT with pre-transplant MRD negativity was associated with better long-term survival. However, infections emerged as a significant complication that may reduce the long-term survival benefits. Trial Registration: ClinicalTrials.gov identifier: ChiCTR1900023957.

BACKGROUND:Higher-risk myelodysplastic syndromes (HR-MDS) carry a high risk of progression to acute myeloid leukemia and poor overall survival. Hypomethylating agents (HMAs), such as azacitidine, remain the standard of care but have limited efficacy. A 15-day venetoclax-azacitidine regimen has shown promising objective response rates (ORR) and potential as a bridge to allogeneic hematopoietic stem cell transplantation (HSCT) in relapsed/refractory HR-MDS. We conducted a prospective multicenter trial to evaluate its efficacy and safety in previously untreated patients. METHODS:This multicenter prospective study enrolled treatment-naïve HR-MDS patients (IPSS-R > 3.5). Venetoclax was administered on days 1-15 (escalated from 100 to 400 mg), combined with azacitidine (75 mg/m2) on days 1-7 of each 28-day cycle. The primary endpoint was ORR (2006 IWG criteria); secondary endpoints included complete remission (CR), overall survival (OS), and AML progression. RESULTS:Twenty-eight patients (median age: 63 years) were enrolled, with a median follow-up of 8.5 months. ORR was 85.7% per 2006 IWG (CR: 35.7%, marrow CR: 50.0%), and 78.6% per 2023 IWG (CR: 35.7%). Responses were consistent across molecular and IPSS-R subgroups. Median OS was not reached. High neutrophil count and high cytogenetic risk were favorable factors; TP53 mutation/deletion was an adverse prognostic marker. Grade 3-4 hematologic toxicities included neutropenia (96.4%), anemia (71.4%), and thrombocytopenia (64.3%). Serious adverse events (35.7%) were mainly infections. No dose-limiting or unexpected toxicities were observed. CONCLUSIONS:The 15-day venetoclax plus azacitidine regimen demonstrated high efficacy and manageable toxicity in treatment-naïve HR-MDS. It may be particularly beneficial for patients with high neutrophil counts, adverse cytogenetics, or those eligible for HSCT, supporting further investigation in larger trials.

Background:Patients with multiple myeloma (MM) and renal impairment (RI), particularly those requiring dialysis, have historically experienced poor outcomes. Despite advancements in targeted therapies, the prognosis of dialysis-dependent MM and factors influencing dialysis independence remain unclear. Objectives:This study aimed to provide a comprehensive analysis of the clinical manifestations and treatment outcomes of dialysis-dependent MM patients in China, and to explore the factors associated with dialysis independence and long-term survival. Design:We conducted a multicenter, retrospective, real-world cohort study. Methods:This multicenter, retrospective study included 122 MM patients requiring chronic hemodialysis (⩾28 days of treatment) at 4 comprehensive hospitals in China from January 2012 to November 2023. Hemodialysis resulting from causes other than MM was excluded. Logistic regression was employed for multivariate analysis of factors associated with dialysis independence, and Kaplan-Meier survival curves and Cox proportional hazard models were utilized for survival analysis. Results:Among the 122 patients, 74 patients (60.7%) were male, with a median age of 65 (39-87) years. Of these, 71.3% (n = 87) had newly diagnosed MM (NDMM), and 28.7% (n = 35) had relapsed/refractory MM (RRMM). Dialysis independence was achieved in 27 patients (22 with NDMM and 5 with RRMM). Proteasome inhibitors were used in 80.3% of patients (n = 98), while 13.9% (n = 17) received daratumumab-based regimens. After a median follow-up of 43.7 months, the median progression-free survival (PFS) was 14.4 months (95% confidence interval (CI): 3.6-25.2), and the median overall survival (OS) was 27.4 months (95% CI: 6.9-47.9). Dialysis-independent patients had significantly longer PFS (36.7 vs 9.4 months, p = 0.006) and OS (62.6 vs 17.7 months, p < 0.001). Factors associated with dialysis independence included achieving a very good partial response (VGPR), receiving daratumumab-based regimens, reduction in serum-free light chain ⩾80% after the first chemotherapy cycle, and age <65 years. Conclusion:In the era of new drugs, dialysis-dependent MM still has a poor prognosis, although dialysis independence improves survival.

Venetoclax (VEN) has shown promising efficacy when combined with intensive chemotherapy regimens—such as FLAG-IDA (DiNardo et al. 2025), DA (Mantzaris et al. 2025), and others—in newly diagnosed acute myeloid leukemia (AML). While current risk classification systems such as the European LeukemiaNet 2022 (ELN2022) for intensive chemotherapy and ELN2024 for VEN plus hypomethylating agents (VEN+HMA) provide standardized frameworks, they may not fully capture the prognostic heterogeneity among patients receiving VEN-based intensive therapy. To address this gap, we conducted a real-world study to construct a refined prognostic model based on molecular features for patients receiving VEN-intensive regimens (ICV) in the first two treatment cycles. Eligible patients were newly diagnosed with AML and received venetoclax in combination with intensive chemotherapy during the first and/or second induction cycle. Therapy regimens included venetoclax with or without a hypomethylating agent (VEN±HMA), combined with one of the following: homoharringtonine-based therapy, anthracycline-based regimens, purine analog-containing regimens, or intermediate-/high-dose cytarabine-based protocols. A total of 409 newly diagnosed AML patients were included. The median age was 49 years (range 11–76), with 37.9% diagnosed with acute monocytic leukemia. Complex or monosomal karyotypes (CK/MK) were observed in 8.1%. Fusion genes included RUNX1-RUNX1T1 (14.2%), CBFB-MYH11 (8.8%) and inv(3) (1.0%). Additional cytogenetic abnormalities included -17/del(17p) (1.5%), -7 (4.2%), and -5/del(5q) (2.0%). Frequently mutated genes included FLT3-ITD (21.8%), NPM1 (17.8%), CEBPA bZIP (9.0%), KMT2A rearrangement (7.3%), RUNX1 (6.1%), and TP53 (3.7%). Univariable analysis revealed that inv(3), -5/del(5q), -7, CK/MK, and mutations in TP53, FLT3-ITD and RUNX1 were significantly associated with inferior OS, whereas RUNX1-RUNX1T1, CBFB-MYH11, and mutated NPM1 without FLT3-ITD conferred favorable survival. The prognosis was not significantly associated with monocytic development (p=0.640). Using a bootstrap-based variable selection approach with the random survival forest algorithm and Cox proportional hazards models, we identified several top significant “beneficial” and “harmful” genetic and cytogenetic features. Based on these results, we developed a novel risk model (ICV-CHN) which stratified patients into four molecularly defined risk groups. The favorable-risk category comprised patients with CBFB-MYH11, RUNX1-RUNX1T1, or mutated NPM1 without FLT3-ITD. Patients with intermediate-risk features were further divided based on their risk gene profiles. The Intermediate-1 group comprised patients not fitting other risk categories, representing standard/unclassified risk. The Intermediate-2 group included those with moderately adverse features such as CK/MK, -7, -5/del(5q), or mutations in RUNX1 or FLT3-ITD—known to attenuate outcomes despite potential sensitivity to targeted therapy. And the adverse-risk category included patients harboring inv(3) or TP53 mutations. According to the ICV-CHN model, the 2-year OS rates of low-risk/intermediate-risk-1 patients were 87.0% with chemotherapy alone and 90.2% with transplantation (p=0.350), while those of intermediate-risk-2/high-risk patients were 47.8% and 73.2%, respectively (p<0.001). Comparative analyses demonstrated that the ICV-CHN model outperformed ELN-based classifications. Under ELN2022, pairwise log-rank tests showed no significant OS difference between intermediate- and adverse-risk groups (p=0.440), with a 2-year time-dependent area under the curve (AUC) of 0.66 and concordance index (c-index) of 0.644. ELN2024 yielded statistically significant pairwise differences but had a lower 2-year AUC of 0.62 and c-index of 0.617. In contrast, the ICV-CHN 2025 model demonstrated significant OS separation across all strata (2-year OS: Fav. vs Int1 vs Int2 vs Adv: 91.4% vs 82.9% vs 68.1% vs 24.3%, p<0.001), with a mean 2-year AUC of 0.73 and mean c-index of 0.72, indicating improved prognostic performance. The model was further verified in an external validation cohort. In concclusion, the ICV-CHN model offers a molecularly grounded and clinically applicable risk stratification framework for AML patients undergoing VEN-intensive therapy. This model enhances outcome prediction beyond current ELN classifications and may support more personalized treatment approaches in real-world settings.

Plasma Cell Leukemia (PCL) is a rare and highly aggressive plasma cell disorder, typically categorized into primary Plasma Cell Leukemia (pPCL) and secondary Plasma Cell Leukemia (sPCL). PCL patients present with more severe clinical symptoms and biological abnormalities. Due to its rarity and heterogeneity, there is currently no standard treatment protocol for this condition. This retrospective study included 100 PCL patients (circulating plasma cells [CPCs] ≥5%) from five tertiary hospitals in China, enrolled between September 2012 and May 2025. Chi-square tests or Fisher's exact test were used for categorical variables, while continuous variables between groups were compared using the nonparametric Mann–Whitney U test. Survival analysis was performed using Kaplan-Meier curves and Cox proportional hazards models. Of the 100 patients, 52 (50.9%) were male, with a median age of 63 years (range, 17-86 years). The median percentage of CPCs was 27.7% (range, 5.0-94.6%). Among the cohort, 62 (62.0%) were pPCL and 38 (38.0%) were sPCL. Compared to pPCL patients, sPCL patients exhibited lower hemoglobin (65 vs. 82 g/L, P = 0.002), platelet counts (40 vs. 89 ×10^9/L, P < 0.001), and albumin levels (32.6 vs. 38.7 g/L, P = 0.015), while lactate dehydrogenase (LDH) levels were elevated (463 vs. 327 U/L, P = 0.027). Furthermore, a higher proportion of sPCL patients were classified as R-ISS stage III (62.3% vs. 49.7%, P = 0.014), although the proportion of high-risk cytogenetic abnormalities did not differ significantly (77.8% vs. 72.7%, P = 0.428). In terms of treatment regimens, a higher proportion of pPCL patients (82.3%, 51/62) received a proteasome inhibitor-based triplet regimen compared to sPCL patients (28.9%, 11/38; P = 0.002). Conversely, a greater proportion of sPCL patients (34.2%, 13/38) received a daratumumab-based quadruplet regimen compared to pPCL patients (9.7%, 6/62; P < 0.001). Notably, 14.5% (9/62) of pPCL patients and 18.4% (7/38) of sPCL patients underwent CAR T-cell therapy. Hematopoietic stem cell transplantation (HSCT) was performed in 24.2% (15/62) of pPCL patients, with 60.0% (9/15) receiving autologous transplant and 40% (6/15) undergoing allogeneic transplant. None of the sPCL patients received HSCT. Clinically, sPCL patients had significantly lower hematologic response rates than pPCL patients, with a ≥ very good partial response (VGPR) rate of 8.0% versus 63.5% (P < 0.001). During a median follow-up period of 10.6 months (range, 0.5-124.5 months), the median progression-free survival (PFS) and overall survival (OS) for the entire cohort were 3.6 months (95% CI, 1.8-5.4 months) and 6.7 months (95% CI, 1.7-11.8 months), respectively, with 69.7% of patients having died during the study. pPCL patients exhibited longer median OS compared to sPCL patients (16.6 vs. 1.6 months, P < 0.001). Among pPCL patients, receiving HSCT significantly improved OS (33.0 vs. 9.5 months, P = 0.008), with no survival advantage between autologous and allogeneic transplants (38.3 vs. 34.8 months, P = 0.661). Treatment with proteasome inhibitor-based triplet or daratumumab-based quadruplet regimens showed no notable difference in survival outcomes within the entire cohort or across PCL subtypes. However, patients who underwent CAR T-cell therapy exhibited superior outcomes across both pPCL and sPCL groups. Multivariate analysis revealed that extramedullary disease (HR 4.504, P = 0.028), elevated LDH (HR 2.292, P = 0.019), and CAR T-cell therapy (HR 0.207, P = 0.036) were independently associated with OS in sPCL patients. Among pPCL patients, independent predictors of OS included HSCT (HR 0.344, P = 0.043), achieving at least a ≥VGPR (HR 0.307, P = 0.003), elevated LDH (HR 2.706, P = 0.022), and thrombocytopenia (HR 2.348, P = 0.032). Despite the advent of novel therapies, the prognosis of PCL remains poor. pPCL patients generally have a better response to treatment than sPCL patients, and HSCT remains a key therapeutic option. CAR T-cell therapy may represent a promising treatment modality for PCL patients in the future.

Objectives:Differentiation hierarchies in myeloid malignancies influence therapeutic response and prognosis. Acute myeloid leukaemia (AML) with t(8;21) is one of the most recurrent genetic subtypes of AML and is considered a distinct entity with shared characteristics. However, clinical outcomes remain markedly heterogeneous. This study aimed to investigate the relationship between leukaemic arrest at specific differentiation stages, genomic profiles and clinical outcomes in t(8;21) AML. Methods:We conducted a retrospective study involving 338 patients with t(8;21) AML from three clinical centres in China. Patients received either chemotherapy alone (49.11%, n = 166) or chemotherapy followed by allogeneic haematopoietic stem cell transplantation (allo-HSCT; 41.72%, n = 141). Immunophenotypic profiling classified patients into progenitor subgroups: MPP (20.12%, n = 68), lymphoid-primed multi-potent progenitor (14.50%, n = 49), CMP (12.72%, n = 43), GMP (24.85%, n = 84) and GP/MP (10.36%, n = 35). Based on differentiation stage, patients were categorised as primitive (Immuno-Prim; 47.34%, n = 160) or monocytic (Immuno-Mono; 35.21%, n = 119). Results:The Immuno-Mono group was associated with lower 2-year overall survival (OS) and a higher 2-year cumulative incidence of relapse (CIR) compared to the Immuno-Prim group. Patients with a KIT mutation had poorer 2-year OS and higher 2-year CIR than those without the mutation. In the allo-HSCT cohort, the Immuno-Mono group continued to show lower 2-year OS and higher 2-year CIR relative to the Immuno-Prim group. Neither gene mutations (aside from KIT) nor chromosomal losses significantly affected OS or CIR. Conclusions:Leukaemic differentiation stage independently predicts post-treatment outcomes in t(8;21) AML. Arrest at specific myeloid stages correlates significantly with genetic aberrations, clinical presentation, therapeutic response and survival.

According to the 2022 International Consensus Classification (ICC) guidelines, nine myelodysplasia-related (MDS-related) gene mutations are classified as adverse-risk markers in acute myeloid leukemia (AML) under intensive therapy (INT). Although venetoclax (VEN) has demonstrated clinical benefit in subsets of AML with MDS-related gene mutations (AML-MR), its efficacy across all nine mutations remains unclear. In this retrospective study involving 453 AML-MR patients, the overall composite complete remission (CRc) rate was 62.6% (275/439). Among fit patients receiving INT, 57.7% (86/149) achieved CRc after a single cycle of induction therapy (IND1), while 62.7% (79/126) of unfit patients receiving low-intensity therapy (LIT) achieved CRc after IND1. VEN significantly improved CRc rates in unfit patients treated with LIT (45.9% vs. 30.0%, P = 0.002), but not in fit patients receiving INT (61.1% vs. 45.0%, P = 0.052). In both groups, CRc after IND1 was strongly associated with improved overall survival (OS). Subgroup analysis showed that hematopoietic stem cell transplantation (HSCT) significantly prolonged OS and relapse-free survival (RFS) in patients without favorable-risk cytogenetics (P = 0.002 for OS, P < 0.001 for RFS), but conferred no survival benefit in those with favorable-risk cytogenetics (P = 0.119 for OS, P = 0.437 for RFS). These findings support the use of VEN to enhance early remission and survival outcomes in unfit AML-MR patients and suggest that HSCT should be considered primarily in those lacking favorable-risk cytogenetics.

Importance:A combination of tyrosine kinase inhibitors and chimeric antigen receptor (CAR) T cells has made a breakthrough in refractory or relapsed Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). However, it remains unclear if this treatment in newly diagnosed Ph-positive ALL is associated with high rates of complete molecular remission (CMR) and leukemia-free survival. Objective:To evaluate the efficacy and safety of dasatinib in combination with CAR T cells as frontline therapy in adults with newly diagnosed Ph-positive ALL. Design, Setting, and Participants:This trial was conducted at a single center, the First Affiliated Hospital of Zhejiang University School of Medicine. Patients were enrolled in this phase 2, single-arm nonrandomized clinical trial between March 5, 2021, and April 13, 2024. The data cutoff date was February 10, 2025. The data analysis was conducted on February 11, 2025. The median duration of follow-up was 23.9 (range, 7.3-47.7) months. A total of 29 adults with newly diagnosed Ph-positive ALL and adequate organ function were screened for eligibility, and 1 patient who received a diagnosis of blast-phase chronic myeloid leukemia was excluded. Intervention:Dasatinib was administered with a 2-week vindesine and dexamethasone regimen as induction, followed by sequential CD19 and CD22 CAR T-cell therapies and single-agent dasatinib maintenance. Main Outcomes and Measures:The primary end point was CMR rate after CD19 CAR T-cell therapy. CMR was defined as undetectable BCR/ABL1 transcripts as measured by quantitative reverse transcription polymerase chain reaction with a sensitivity of 10-4 in the bone marrow. Results:Twenty-eight patients (median [range] age, 48.5 [18.0-69.0] years; 10 female individuals [36%]) were enrolled, and 1 patient withdrew after induction. The CMR rate was 25% (7 of 28) after induction and increased to 85% (23 of 27) after CD19 CAR T-cell therapy. Twenty-five patients (89.3%) received sequential CD22 CAR T-cell therapy, and the CMR rate was 76% (19 of 25). Of the 52 CAR T-cell therapies, only 21 cases of grade 1 cytokine release syndrome occurred. After a median follow-up of 23.9 (range, 7.3-47.7) months, the 2-year overall survival and leukemia-free survival were 92%. Conclusions and Relevance:The results of this nonrandomized clinical trial suggest that the combination of dasatinib and CAR T-cell therapy showed encouraging efficacy in newly diagnosed Ph-positive ALL with acceptable toxic effects. Further studies with larger cohorts and longer follow-up durations are needed. Trial Registration:ClinicalTrials.gov Identifier: NCT04788472.

Malignant plasma cell proliferation characterizes multiple myeloma (MM), a hematologic disease. Bortezomib (BTZ) is a protease inhibitor that has been approved for the treatment of MM. Nevertheless, the effectiveness of BTZ is frequently impeded by drug resistance, and the mechanisms responsible for this phenomenon remain incompletely understood. A growing body of evidence indicates that N6-methyladenosine (m6A) plays crucial roles in a wide range of biological functions. However, the impact of m6A on the response of MM cells to BTZ is poorly understood. In our recent research, we discovered that METTL3 facilitated the m6A alteration of lncRNA H19, providing MM cells with resistance to BTZ. Additional examination revealed that H19 functioned as a sponge to negatively regulate the expression of miR-184 in MM cells. Furthermore, we discovered that H19 binds to miR-184, a tumor suppressor, in MM cells. In MM cells, miR184 can suppress the expression of CARM1 by targeting its 3'-UTR. In conclusion, rescue trials have validated the significance of the METTL3/H19/miR-184/CARM1 pathway in determining the susceptibility of cells to BTZ. Consequently, directing efforts toward this pathway could prove to be a powerful approach for enhancing the effectiveness of BTZ for MM therapy.

Intravascular large B-cell lymphoma (IVLBCL) is a rare and highly aggressive lymphoma, but current knowledge is still inadequate. We retrospectively analyzed 50 IVLBCL patients from five Chinese tertiary hospitals in China between 2017 and 2024. Hemophagocytic variant (HV) patients showed worse performance status, universal B symptoms, more bone marrow infiltration, higher mortality, pancytopenia, elevated inflammatory markers (CRP, LDH, ferritin), hypoglobulinemia and hypogammaglobulinemia. Among 46 treated patients, CR/CRu rate was 71% (27/38). The 2-year OS was 65.5%, significantly worse in HV vs. classical variant (CV) (43.3% vs. 76.4%, P = 0.007). Multivariate analysis identified CNS involvement (HR = 10.86, P < 0.001), HV subtype (HR = 1.91, P = 0.018), and nodal organs involvement (HR = 5.26, P = 0.052) as poor prognostic factors. IVLBCL exhibits marked heterogeneity, with HV and CNS involvement conferring dismal outcomes. This study provides key diagnostic/therapeutic insights for IVLBCL in China, warranting prospective trials to validate prognostic models and optimize therapies.

The RAS pathway and developmental stage are known to influence leukemic cell proliferation and drug resistance. However, their impact on the prognosis of acute myeloid leukemia (AML) patients, particularly post-allo-HSCT, remains unclear. This study aimed to explore the effects of RAS-pathway mutations and developmental stage on the outcomes of AML patients who received allo-HSCT. A total of 364 consecutive adult AML patients who underwent their first allo-HSCT with myeloablative conditioning were enrolled in this study. The primary endpoint of this study was the cumulative incidence of relapse (CIR) and secondary endpoints were OS and leukemia-free survival (LFS). RAS-pathway mutations were detected in 57 patients (15.7