Effects of different conditioning regimens on HLA-mismatched microtransplantation and changes in fine immune indices in acute myeloid leukaemia.

The aim of this study was to observe the effects of different conditioning regimens on fine immune indices after microtransplantation (MST) in patients with acute myeloid leukaemia (AML). This article discusses the possible immune mechanism of microtransplantation and describes a more optimized conditioning regimen. A total of 55 AML patients who received MST treatment at the Second Hospital of Lanzhou University from August 2015 to October 2023 were included in this study, and 13 AML patients who did not receive MST but directly received the maintenance therapy were included as the control group (C). The MST patients were divided into a conditioning regimen with venetoclax group (A) and a conditioning regimen without venetoclax group (B). The fine immune indices were detected by flow cytometry and cytometric bead array analysis. Changes in the immune indices before and after treatment were observed, and the progression-free survival (PFS) and overall survival (OS) of patients in the MST group were analysed. Compared with those in Group B, patients in Group A had better PFS and OS. The proportion of Treg cells and the expression level of IL-2 were increased, while TNF-α and IFN-α were decreased after MST (P < 0.05). In Group B, total T cells, CD4+T cells and CD4+/CD8+T cells decreased; NK cells and total B cells increased; and IL-17A first increased and then decreased during the MST (P < 0.05). There were significant differences in total B cells, IL-4 and IFN-γ between Group A and Group B during MST. Moreover, there were significant differences in total T cells, CD4+T cells, Treg cells, IL-17A, IFN-γ and IL-2 between the patients in the MST group and those in the control group (P < 0.05). The MST conditioning regimen containing venetoclax significantly changed the fine immune indices and showed improved efficacy, which is worthy of further study and clinical application.

Seven-Day Vonoprazan-Based Triple Therapy as First-Line Helicobacter pylori Treatment in Comparison With Extended Sequential Therapy: A Randomized Controlled Trial.

BACKGROUND: Vonoprazan, a potassium-competitive acid blocker, has demonstrated greater potency and a longer duration of acid suppression when compared to the proton pump inhibitors. However, data regarding the comparison between vonoprazan-based triple therapy with standard treatment for first-line Helicobacter pylori treatment are limited. This study aimed to compare the efficacy between 7-day vonoprazan-based triple therapy with high-dose amoxicillin (VAC-7) and 14-day extended sequential therapy (S-14). MATERIALS AND METHODS: This was a single-center prospective randomized controlled trial following a noninferiority design. Subjects over 20 years old with confirmed H. pylori infection were enrolled prospectively from Fu Jen Catholic University Hospital. They were randomly assigned to the VAC-7 or S-14 group. The primary endpoint was the eradication rate in first-line treatment, evaluated by urea breath test, with noninferiority determined using the Farrington-Manning method. The secondary outcome included adverse effect rates and compliance, assessed through self-administered questionnaires. RESULTS: Between December 2021 and June 2023, a total of 628 patients were recruited. The eradication rates by per-protocol analysis and intention-to-treat analysis were 88.6%/81.8% for VAC-7 and 90.3%/81.4% for S-14, respectively. The VAC-7 was non-inferior to S-14 in terms of ITT analysis. Subjects experienced fewer incidences of nausea, anorexia, dizziness, fatigue, and any severe adverse events in the VAC-7 group. Compliance was higher in the VAC-7 group, with 94% taking all the pills correctly. CONCLUSIONS: Our findings supported the use of 7-day vonoprazan triple therapy with high-dose amoxicillin as the standard first-line treatment for H. pylori infection. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05371249.

Venetoclax is effective for chronic myelomonocytic leukemia blastic transformation with RUNX1 mutation.

Background: Chronic myelomonocytic leukemia is a clonal hematological disorder with an inherent risk of transformation to acute myeloid leukemia. Recently, there has been exponential discovery of molecular abnormalities in patients with chronic myelomonocytic leukemia. Some of these mutations independently contribute to a higher risk of transformation and result in inferior overall survival. Treatment strategies for patients undergoing blastic transformation in chronic myelomonocytic leukemia, especially after progressing on hypomethylating agents, are currently limited.Case presentation: We present a case of a 70-year-old male patient with chronic myelomonocytic leukemia blastic transformation with RUNX1 mutation following azacitidine monotherapy. Notably, he achieved hematological complete remission after the first course of venetoclax plus azacitidine, leading to the disappearance of RUNX1 mutation. We performed serial assessments of molecular analysis by next generation sequencing throughout his clinical course.Conclusion: The presence of RUNX1 mutation is associated with higher response rates to venetoclax-based combination therapies in chronic myelomonocytic leukemia with blastic transformation. Our findings suggest that even after azacitidine monotherapy, venetoclax plus azacitidine is effective in targeting leukemic clones harboring RUNX1 mutations. Furthermore, we emphasize the significance of molecular analysis, including next-generation sequencing, in providing insights into the detailed dynamics of clonal evolution and guiding treatment decisions.

Association between 24-hour blood pressure parameters and 90-day functional outcome in acute ischemic stroke patients with early anticoagulation.

This study aimed to examine the relationship between blood pressure (BP) and blood pressure variability (BPV) during the first 24 hours from admission with 90-day functional outcomes in acute ischemic stroke (AIS) patients whose onset within 24 hours and receiving early argatroban treatment. The study recruited 214 AIS patients. BP was monitored using a cuff at 1-hour fixed intervals, and BP/BPV parameters [standard deviation (SD), coefficient of variation (CV), successive variation (SV), and average real variability (ARV)] were collected. Age, the National Institutes of Health Stroke Scale (NIHSS) score at admission, previous history of diabetes mellitus (DM), and infarction site (located in anterior circulation) were identified as independent factors affecting 90-day outcomes in multiple logistic regression. After adjusting for confounding variables, association between BP/BPV and 90-day modified Rankin Scale (mRS) was assessed using logistic regression models. In model 1 (adjusted for age and NIHSS score at admission), mean-systolic blood pressure (SBP) showed association with 90-day outcomes [1.068 (1.008, 1.131), P = .025]. In model 2 (adjusted for age, NIHSS score at admission, previous history of DM), mean-SBP [1.061 (1.001, 1.123), P = .045] and max-SBP [0.951 (0.906, 0.998), P = .040] showed relatively weak association with outcomes. In model 3 [adjusted for age, NIHSS score at admission, previous history of DM, infarct site (located in anterior circulation)], all BP values were not related with outcomes, meanwhile, none of the BPV parameters calculated from SBP, diastolic blood pressure and mean arterial pressure showed association with 90-day outcomes. Future prospective studies are required to assess the relationship between early BP/BPV parameters with 90-day outcomes and further clarify the reference values for BP parameters. This is important for effective BP/BPV management and improved patient prognosis.

Vonoprazan-amoxicillin dual therapy for Helicobacter pylori eradication in Chinese population: A prospective, multicenter, randomized, two-stage study.

BACKGROUND: The efficacy of Vonoprazan-amoxicillin dual therapy (VAT) in the treatment of Helicobacter pylori (H. pylori) is controversial. AIM: To evaluate the efficacy of VAT in the Chinese population. METHODS: This prospective, multicenter, randomized, open-label, and two-stage study was conducted at 23 centers in Fujian, China (May 2021-April 2022). H. pylori-infected patients were randomized to bismuth quadruple therapy (BQT), BQT-Vonoprazan (BQT-V), seven-day VAT (VAT-7), ten-day VAT (VAT-10), and fourteen-day VAT (VAT-14) groups. The primary endpoint was the H. pylori eradication rate. The secondary endpoint was the frequency of adverse events. This study was registered with the Chinese Clinical Trial Registry, ChiCTR2100045778. RESULTS: In the first stage, VAT-7 and BQT-V groups were selected for early termination because less than 23 among 28 cases were eradicated. In the second stage, the eradication rates for BQT, VAT-10, and VA-14 were 80.2% [95% confidence interval (95%CI): 71.4%-86.8%], 93.2% (86.6%-96.7%), 92.2% (85.3%-96.0%) in the intention-to-treat (ITT) analysis, and 80.9% (95%CI: 71.7%-87.5%), 94.0% (87.5%-97.2%), and 93.9% (87.4%-97.2%) in the per-protocol analysis. The ITT analysis showed a higher eradication rate in the VAT-10 and VAT-14 groups than in the BQT group (P = 0.022 and P = 0.046, respectively). The incidence of adverse events in the VAT-10 and VAT-14 groups was lower than in the BQT group (25.27% and 13.73% vs 37.62%, respectively; P < 0.001). CONCLUSION: VAT with a duration of 10 or 14 days achieves a higher eradication rate than the BQT, with a more tolerable safety profile in H. pylori-infected patients in Fujian.

Recalcitrant multi-variant lichen planus successfully treated with oral baricitinib and topical ruxolitinib cream.

Lichen planus is a chronic auto-inflammatory disease that primarily affects mucocutaneous regions. There are many variants of lichen planus including cutaneous, oral, nail, follicular, and erosive forms. Without any disease-specific treatment options, multi-variant lichen planus can be a challenging disease to manage. We present a 61-year-old woman with multivariant lichen planus that was refractory to numerous systemic and topical therapies. Subsequently, her cutaneous and vulvovaginal lesions improved with the use of oral baricitinib and the erosive oral lesions improved with topical ruxolitinib.

Spatial Variation of the Gastrointestinal Microbiota in Response to Long-Term Administration of Vonoprazan in Mice With High Risk of Gastric Cancer.

BACKGROUND: Vonoprazan, a potassium-competitive acid blocker, is superior to traditional proton pump inhibitor (PPI) in acid suppression and has been approved in the treatment of acid-related disorders. Accumulating evidence suggest associations between PPI use and gut microbiota, yet the effect of vonoprazan on GI microbiota is obscure. METHODS: Transgenic FVB/N insulin-gastrin (INS-GAS) mice as a model of gastric cancer (GC) were administered vonoprazan by gavage every other day for 12 weeks. Stomachs were evaluated by histopathology, Ki-67 proliferation index, and inflammatory cytokines. The mucosal and lumen microbiota from stomach, jejunum, ileum, cecum, and feces were detected using 16S rRNA gene sequencing. RESULTS: Higher incidence of intestinal metaplasia and epithelial proliferation were observed in the vonoprazan group than that in the control mice. Vonoprazan also elevated the gastric expression of proinflammatory cytokines, including TNF-α, IL-1ß, and IL-6. Each mice comprised a unique microbiota composition that was consistent across different niches. The structure of GI microbiota changed dramatically after vonoprazan treatment with the stomach being the most disturbed segment. Vonoprazan administration shifted the gut microbiota toward the enrichment of pathogenic Streptococcus, Staphylococcus, Bilophila, and the loss of commensal Prevotella, Bifidobacterium, and Faecalibacterium. Interestingly, compared to the controls, microbial interactions were weaker in the stomach while stronger in the jejunum of the vonoprazan group. CONCLUSIONS: Long-term vonoprazan treatment promoted gastric lesions in male INS-GAS mice, with the disequilibrium of GI microbiome. The clinical application of vonoprazan needs to be judicious particularly among those with high risk of GC.

Vonoprazan-Amoxicillin Dual Therapy With Different Amoxicillin Administration Regimens for Helicobacter pylori Treatment: A Randomized Controlled Trial.

BACKGROUND: The effect of preprandial or postprandial administration of amoxicillin on the efficacy of vonoprazan-amoxicillin dual therapy (VA-dual therapy) for Helicobacter pylori treatment has not been studied. It is also unclear whether amoxicillin dosing four times daily is more effective than three times daily. We aimed to investigate the effect of different amoxicillin administration regimens on the efficacy of VA-dual therapy. MATERIALS AND METHODS: H. pylori-infected subjects were randomly assigned to three groups in a 1:1:1 ratio to receive a 14-day dual therapy consisting of vonoprazan 20 mg twice daily + amoxicillin 1000 mg three times daily before meals (BM-TID) or 1000 mg three times daily after meals (AM-TID) or 750 mg four times daily after meals (AM-QID). H. pylori eradication rates, adverse events rates, compliance, and antibiotic resistance were compared. RESULTS: Between May 2021 to April 2023, 327 subjects were enrolled. The eradication rates of BM-TID, AM-TID, and AM-QID dual therapy were 88.1%, 89.9%, and 93.6% in intention-to-treat (ITT) analysis, 90.6%, 94.2%, and 99.0% in modified ITT (MITT) analysis, and 90.4%, 94.1%, and 99.0% in per-protocol (PP) analysis. Although there was non-inferiority between BM-TID and AM-TID, as well as between AM-TID and AM-QID, AM-QID was significantly more effective than BM-TID. There were no significant differences in adverse event rates, compliance, and antibiotic resistance among the three groups. CONCLUSIONS: Postprandial administration and the increased frequency of administration of amoxicillin may contribute to a better efficacy of VA-dual therapy, especially for rescue therapy. All VA-dual therapy in our study could achieve good efficacy for first-line treatment. TRIAL REGISTRATION: clinicaltrials.gov: NCT05901051.

[Venetoclax combined with dose-reduced HAD as induction treatment for patients with de-novo acute myeloid leukemia].

The efficacy and safety of venetoclax combined with reduced dose HAD regimen in the treatment of newly diagnosed acute myeloid leukemia (AML) was investigated. From May 2022 to January 2023, a total of 25 patients with newly diagnosed AML were treated with venetoclax combined with reduced-dose HAD regimen as induction therapy. Accoding to the 2017 ELN recommendations, 13 (52.0%) in favoable, 3 (12.0%) in intemediate, and 9 (36.0%) in adverse. The ORR (CR rate+PR rate) was 88.0%, and the CR rate was 84.0%. By May 30, 2023, with a median follow-up of 9 months, 1 year overall survival, event-free survival, and relapse-free survival were 100%, 94.7%, and 94.7%, respectively. All patients received 1-5 cycles of consolidation therapy and two median cycles. Treatment with venetoclax and reduced dose of HAD regimen in the treatment of patients with newly diagnosed AML was high effective and safe.

Effect of ripasudil after trabeculectomy with mitomycin C: a multicentre, randomised, prospective clinical study.

BACKGROUND: To investigate if there are improvements in trabeculectomy outcomes supporting filtration bleb formation caused by Rho-associated protein kinase (ROCK) inhibitors. METHODS: This prospective, multicentre, randomised, open-label clinical study examined open-angle glaucoma patients who underwent trabeculectomy or trabeculectomy combined with cataract surgery followed by 3-month postoperative ripasudil treatments. After randomly allocating patients to ripasudil-ROCK inhibitor (ripasudil) or without ripasudil (non-ripasudil) groups. Mean intraocular pressure (IOP) changes, success rate, and number of eyedrops were compared for both groups. RESULTS: A total of 17 and 15 subjects dropped out in the ripasudil group and non-ripasudil group, respectively. At baseline, the mean IOP was 16.8±5.0 mm Hg in the ripasudil group (38 patients) and 16.2±4.4 in the non-ripasudil group (52 patients). The IOP decreased to 11.4±3.2 mm Hg, 10.9±3.9 mm Hg and 10.6±3.5 mm Hg at 12, 24 and 36 months in the ripasudil group, while it decreased to 11.2±4.1 mm Hg, 10.5±3.1 mm Hg and 10.9±3.2 mm Hg at 12, 24 and 36 months in the non-ripasudil group, respectively. There was a significant decrease in the number of IOP-lowering medications after trabeculectomy in the ripasudil group versus the non-ripasudil group at 24 (p=0.010) and 36 months (p=0.016). There was no statistically significant difference between the groups for the 3-year cumulative probability of success. CONCLUSION: Although ripasudil application did not increase the primary trabeculectomy success rate, it did reduce IOP-lowering medications after trabeculectomy with mitomycin C.

Effect of perioperative tamsulosin on successful ureteral access sheath placement and stent-related symptom relief: A double-blinded, randomized, placebo-controlled study.

PURPOSE: This study investigated the effect of administering tamsulosin before surgery on the successful insertion of a 12/14 French (F) ureteral access sheath (UAS) during the procedure, as well as the impact of preoperative and postoperative tamsulosin use on symptoms related to the ureteral stent. MATERIALS AND METHODS: This study was a randomized, single-center, double-blinded, placebo-controlled trial involving 200 patients who underwent unilateral retrograde intrarenal surgery. Patients received either tamsulosin (0.4 mg) or placebo 1 week before surgery until stent removal. Patients were randomly assigned to one of four groups. Group 1 received tamsulosin throughout the study period. Group 2 received tamsulosin before surgery and placebo after surgery. Group 3 received placebo before surgery and tamsulosin after surgery. Group 4 received placebo before and after surgery. The USSQ (Ureteral Stent Symptom Questionnaire) was completed between postoperative days 7 and 14 immediately before stent removal. RESULTS: A total of 160 patients were included in this analysis. Their mean age was 55.0±11.0 years, and 48 patients (30.0%) were female. In the group that received preoperative tamsulosin, the success rate of 12/14F UAS deployment was significantly higher than that of the preoperative placebo group (88.0 vs. 75.3%, p=0.038). Preoperative and postoperative tamsulosin did not significantly alleviate symptoms related to the ureteral stent. CONCLUSIONS: Our results revealed that preoperative administration of tamsulosin improved the success of larger-sized UAS, whereas preoperative and postoperative tamsulosin use did not significantly alleviate symptoms related to ureteral stents.

TPGS nanoparticles co-loaded with ABT-737 and R848 for breast cancer therapy.

The development of new effective drugs to treat breast cancer remains a huge challenge. ABT-737 can inhibit Bcl-2 proteins to promote apoptosis. Resiquimod (R848) is a TLR7/8 agonist that is effective in modulating the immunosuppressive microenvironment. In this study, a codelivery system (TPGS/ABT+R848 NPs) based on D-α-tocopheryl poly (ethylene glycol) 1000 succinate as a potential drug delivery vector to codelivery ABT-737 and R848 was investigated. The size of TPGS/ABT+R848 NPs was 102.5 nm, the drug loading of ABT-737 and R848 was 30.6 % and 12.5 %, and the entrapment efficiency was 84.2 % and 23.7 %, respectively. The nanoparticles showed no significant change in particle size over 14 days. R848 and ABT-737 were released in co-loaded nanoparticles in sequential order. In vitro anti-tumor experiments, the IC50 value of TPGS/ABT+R848 NPs was 0.30 µg·mL-1, 34 times lower than that of free ABT-737. Animal experiments also verified that TPGS/ABT+R848 NPs could enhance the anti-tumor activity, and the tumor weight inhibition rate was 75.3 %. This study demonstrated that TPGS NPs loaded with ABT-737 and R848 have superior combination tumor therapeutic effects, and the co-loaded preparation is conducive to anti-tumor efficacy. The TPGS/ABT+R848 NPs could be a promising platform against breast cancer.

FRACTION: protocol of a phase II study of Fedratinib and Nivolumab combination in patients with myelofibrosis and resistance or suboptimal response to JAK-inhibitor treatment of the German MPN study group (GSG-MPN).

Development of Janus-kinase (JAK) inhibitors has revolutionized the therapeutic landscape for patients with myeloproliferative neoplasia (MPN). Following approval of the first JAK1/2-inhibitor Ruxolitinib, symptoms of this inflammatory disease, characterized by splenomegaly, release of inflammatory cytokines and appearance of thrombosis, could be effectively reduced for the first time. However, JAK-inhibitor treatment is limited in several aspects: 1) duration of response: 3 years after initiation of therapy more than 50% of patients have discontinued JAK-inhibitor treatment due to lack of efficacy or resistance; 2) reduction of disease burden: while effective in reducing inflammation and constitutional symptoms, JAK-inhibitors fail to reduce the malignant clone in the majority of patients and therefore lack long-term efficacy. Early clinical trials for patients with myelofibrosis (MF) have tried to address these issues for patients with suboptimal response to Ruxolitinib therapy while combination therapies with Fedratinib are rare. Recent reports provided first evidence on how the JAK2-V617F mutated myeloid cells may influence T-cell responses. JAK2-V617F promoted the synthesis of PD-L1 in MPN cells leading to limited anti-neoplastic T-cell responses, metabolic changes in T-cells and eventually JAK2-V617F-driven immune-escape of MPN cells. These findings may facilitate the use of immunotherapeutic approaches for JAK-mutated clones. Immune checkpoints refer to a variety of inhibitory pathways that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. The FRACTION study is a single arm, open label Phase II trial investigating the combination of Fedratinib with the PD-1 inhibitor Nivolumab in patients with myelofibrosis and suboptimal or lack of response to JAK-inhibitor therapy. Over a 12 months period the trial assesses longer term outcomes, particularly the effects on clinical outcomes, such as induction of clinical remissions, quality of life and improvement of anemia. No prospective clinical trial data exist for combinations of JAK- and immune-checkpoint-inhibitors in the planned MF study population and this study will provide new findings that may contribute to advancing the treatment landscape for MF patients with suboptimal responses and limited alternatives.

Less is more: An analysis of venetoclax and hypomethylating agent post-induction treatment modifications in AML.

Venetoclax (Ven) combined with a hypomethylating agent (HMA) enhances survival in elderly/unfit acute myeloid leukemia (AML) patients, yet often necessitates regimen modifications due to intolerance. However, it is unclear how these modifications affect patient outcome. This retrospective cohort study evaluates the impact of post-induction HMA/Ven regimen modifications on disease progression and survival. This study reviewed 142 AML patients treated with HMA/Ven within the Northwell Health System from January 2019 to December 2022. To assess the impact of post-induction regimen modifications, patients were grouped according to median days between cycles (≤34 or ≥35 days cycle intervals) and median Ven days per cycle (≤14 or ≥15 days/cycle) based on only cycle 3 and beyond. Kaplan-Meier and Cox proportional hazard regression analyses were employed for univariate and multivariate assessments, respectively. There was no significant difference in median progression-free survival (mPFS)(11.6 vs 11.8 months, p = 0.73) or median overall survival (mOS)(15.1 vs 21.8 months, p = 0.16) between cycle interval groups. However, there was a clinically and statistically significant advantage in mPFS (15.8 vs 8.7 months, p = 0.01) and mOS (24.7 vs 11.3 months, p = 0.006) for patients with a median of ≤14 Ven days/cycle compared to ≥15 Ven days/cycle. Multivariate analysis demonstrated that ≤14 days of Ven for cycle 3 and beyond was an independent predictor of decreased mortality (HR 0.18, CI 0.07-0.48, p = 0.0007). Extended cycle intervals did not adversely affect mortality while reduced Ven duration per cycle post-induction was associated with improved survival in elderly AML patients.

Homoharringtonine may help improve the outcomes of venetoclax and azacitidine in AML1-ETO positive acute myeloid leukemia.

PURPOSE: T(8;21)(q22;q22.1)/AML1-ETO positive acute myeloid leukemia (AE-AML) is sensitive to conventional chemotherapy with a favorable prognosis. However, recent small case reports suggest the limited effectiveness of venetoclax (VEN) and hypomethylating agents (HMA) in treating AE-AML. The aim of this retrospective study was to evaluate the effectiveness of VEN plus AZA (VA) in AE-AML and explore whether adding homoharringtonine (HHT) to VA (VAH) could improve the response. METHODS: Patients who received VEN plus AZA and HHT (VAH) or VEN plus AZA (VA) regimens were included in this retrospective study. The endpoints of this study were to evaluate the rate of composite complete remission (CRc), measurable residual disease (MRD), event-free survival (EFS), overall survival (OS), and relapse between VAH and VA groups. RESULTS: A total of 32 AE-AML patients who underwent VA or VAH treatments (newly diagnosed with VA, ND-VA, n = 8; relapsed/refractory with VA, R/R-VA, n = 10; relapsed/refractory with VAH, R/R-VAH, n = 14) were included. The CR (complete remission) /CRi (CR with incomplete count recovery) rate of ND-VA, R/R-VA and R/R-VAH were 25%, 10%, and 64.3%, respectively. Measurable residual disease (MRD) negative was observed in 66.7% of R/R-VAH and none of VA-R/R patients. Co-occurring methylation mutations are associated with poor outcomes with VA but exhibit a more favorable response with VAH treatment. Additionally, patients with c-kit mutation presented inferior outcomes with both VEN-based regimens. All regimens were tolerated well by all patients. CONCLUSION: Our data confirmed the poor response of VA in AE-AML, whether used as frontline or salvage therapy. Adding HHT to VA may improve outcomes and enhance the efficacy of VEN in this population.

Outcomes of venetoclax-based therapy in patients with t(11;14) light chain amyloidosis after failure of daratumumab-based therapy.

BACKGROUND: Daratumumab's incorporation in the upfront treatment of light chain (AL) amyloidosis has led to daratumumab (dara) refractoriness early in disease course. Patients who experience relapse or have suboptimal response to dara-based-therapy, have limited options. OBJECTIVE: This study aimed to evaluate the outcomes of venetoclax-based therapy in t(11;14) positive AL patients who previously failed dara. METHODS: Thirty-one patients with AL were included in this bi-institutional retrospective analysis. RESULTS: Dara failure was due to inadequate response in 20 (65%) patients, haematologic relapse in 7 (22%), and both haematologic plus organ relapse in 4 (13%). Overall haematologic response rate to venetoclax-based therapy was 97%, with ≥ VGPR being 91%. Of the 19 evaluable patients with cardiac involvement, 14 (74%) achieved organ response. Of the 13 evaluable patients with renal involvement, 6 (46%) achieved organ response. With a median follow-up of 22 months, median time-to-next-treatment (TTNT) and overall survival (OS) were not reached. The 12- and 24-month TTNT rates were 74% and 56%, respectively. At data-cut-off, four patients had died, all from AL-related organ complications. The 12- and 24-month OS rates were 89% and 85%, respectively. Grade ≥3 adverse events occurred in 26% of patients, with 6% due to infections. CONCLUSION: These findings are encouraging for the use of venetoclax as salvage therapy post-dara failure.