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Introduction: The combination of intravenous or intra-arterial thrombolysis with mechanical thrombectomy (MT) for acute ischemic stroke (AIS) has been thoroughly investigated. However, no study has explored the outcomes of combining both intravenous and intra-arterial thrombolysis with MT. Methods: Data from Stroke Thrombectomy and Aneurysm Registry (STAR) from 2013 to 2023 was utilized. We compared AIS patients with LVO who underwent MT with combined intra-venous and intra-arterial thrombolysis (IV+IA) and with intra-venous thrombolysis alone (IV). We performed propensity score (PS) matching between the two groups using age, sex, premorbid mRS, admission NIHSS, occluded vessel, ASPECTS score, time from symptoms onset to arterial puncture, and frontline technique. Primary outcomes were any intracranial hemorrhage (ICH) and symptomatic ICH (sICH). Secondary outcomes included successful recanalization (mTICI ≥2C), early neurological improvement (defined as 4 or more points improvement in NIHSS score in 24 hours), 90-day modified Rankin Scale (mRS) 0-2, mRS 0-1, and mortality. Results: A total of 2495 LVO-related AIS patients were included, consisting of the IA+IV group (n = 266) and the IV group (n = 2228). Propensity matching yielded 192 well-matched patients in each group. No significant differences were observed between the groups in either ICH or sICH (odds ratio [OR]: 0.96, 95% confidence interval [CI]: 0.61-1.52, p = 0.60; OR: 0.92, 95% CI: 0.42-2.03, p > 0.90, respectively). The IA+IV group had a significantly lower proportion of successful recanalization (OR: 0.41, 95% CI: 0.27-0.62, p < 0.001), and early neurological improvement (OR: 0.55, 95% CI: 0.30-1.00). However, 90-day mRS 0-2, mRS 0-1, and mortality rates showed no significant differences between the two groups. Conclusion: The findings of this study suggest that the combined use of IA and IV thrombolysis in AIS patients undergoing MT is safe. Although the IA+IV group demonstrated lower rates of recanalization and early neurological improvement, long-term functional outcomes and mortality rates were comparable to the IV-thrombolysis group, indicating a potential delayed benefit of additional IA thrombolysis therapy.

Introduction: While balloon guide catheters (BGCs) enhance safety and efficacy of mechanical thrombectomy in large vessel occlusions, their impact on distal medium vessel occlusion (DMVO) remains underexplored. This study aimed to compare the outcomes of BGC vs non-BGC in DMVO thrombectomy. Methods: This retrospective study focused on DMVO cases defined as occlusions in M2-M4 middle cerebral artery, anterior cerebral artery, and posterior cerebral artery. Baseline characteristics and technical and clinical outcomes were compared between the two groups, with subgroup analysis in first-line thrombectomy techniques, including ADAPT, stent retriever, and Solumbra. First pass effect (FPE) was defined as a modified Thrombolysis in Cerebral Infarction (mTICI) score ≥ 2C after the first pass. Results: A total of 1,508 patients were included, of whom 231 (15.3%) were in the BGC group and 1,277 (84.7%) were in the Non-BGC group. The BGC group was associated with a lower mTICI score ≥ 2C (overall: 43.2% vs. 52.7%, p = 0.01; ADAPT: 42.2% vs. 57.1%, p = 0.01; Solumbra: 32.4% vs. 51.4%, p = 0.005), longer puncture to intracranial access time (overall: 15 vs. 8 min, p < 0.001; ADAPT: 17 vs. 8 min, p < 0.001; Solumbra: 12 vs. 8 min, p = 0.02), and longer puncture to recanalization time (overall: 97 vs. 35 min, p < 0.001; ADAPT: 100 vs. 28 min, p < 0.001; Solumbra: 78 vs. 46 min, p < 0.001; Stent retriever: 95 vs. 45 min, p < 0.001 ). The BGC group also had a lower FPE rate (17.4% vs. 30.7%, p = 0.03) in the Solumbra subgroup. In terms of clinical outcomes, the BGC group had a lower rate of distal embolization (overall: 8.8% vs. 14.9%, p = 0.02), but there were no significant differences in other clinical outcomes between the two groups in first-line thrombectomy techniques. Conclusions: Our findings showed that the use of BGC in DMVO had a lower mTICI score, reduced FPE rates, decreased distal embolization, and longer procedure times. Figure 1: Figure 2:

Introduction: The efficacy of mechanical thrombectomy (MT) for tandem vertebrobasilar occlusion (tVBO) is not well established in patients with basilar artery occlusion (BAO). Objective: To investigate the treatment outcomes of MT in tVBO. Method: This international, multicenter, retrospective cohort included patients with MT for tVBO and isolated BAO from 2013 to 2023. The primary outcome was the 90-day modified Rankin Scale (mRS) score 0-2. Secondary outcomes included complete recanalization (modified Thrombolysis in Cerebral Ischemia [mTICI] ≥ 2C) and 90-day mortality rate. These outcomes were compared between tVBO and isolated BAO groups. Adjustment factors were age, sex, admission National Institutes of Health Stroke Scale (NIHSS), pre-morbid mRS, onset to groin duration, and intravenous tissue plasminogen activator. Results: Among 10,229 patients, 689 had BAO. Of those, 61 (9.7%) had a tVBO. Median age was 61 [IQR 53-74] years and 29 (47.5%) patients were female. Compared to isolated BAO, tVBO group had lower age (61 [53-74] versus 68 [58-79], P<0.001) and lower admission NIHSS (15 [7 - 22] versus 17 [9-26], P≤0.05). There was no significant difference in the rate of complete recanalization between the two groups (adjusted odds ratio [aOR]: 0.83; 95% CI: 0.39-1.79; P=0.60) However, the tVBO group had significantly lower odds of a favorable outcome compared to the isolated BAO group (aOR: 0.35; 95% CI: 0.13-0.83; P=0.023) and higher odds of 90-day mortality (aOR: 3.51; 95% CI: 1.59-7.85; P=0.002). Binary regression analysis revealed that age (OR 0.98; 95% CI 0.96 - 1.00; P=0.019), admission NIHSS (OR 0.90; 95% CI 0.87-0.93; P<0.001), premorbid mRS (OR 0.71; 95% CI 0.53-0.93; P=0.016), successful recanalization (OR 2.94; 95% CI 1.71-5.15; P<0.001), and tVBO (OR 0.33; 95% CI 0.11-0.86; P=0.031) were significant predictors of 90-day favorable outcome. Conclusion: tVBO was associated with poor outcomes. Further efforts should be aimed at improving outcomes for this subpopulation.

Objective: To determine whether first pass effect (FPE) after mechanical thrombectomy (MT) for anterior circulation large vessel occlusion acute ischemic stroke (LVO-AIS) is modified by procedural time (PT). Methods: The Stroke Thrombectomy and Aneurysm Registry (STAR), a multi-center international dataset, was retrospectively analyzed for anterior circulation LVO-AIS treated by MT who achieved excellent reperfusion (TICI 2c/3). The primary outcome was good functional outcome as defined by a 90-day modified Rankin Scale (mRS) 0-2. The primary study exposure was first pass success (FPS, 1 pass vs ≥2 passes) and the secondary exposure was PT. Logistic regression models were fit-adjusted and marginal effects used to assess the interaction of PT (≤30 vs >30 minutes) and FPS, adjusting for potential confounders including time from last known well to start of MT. Results: A total of 1,310 patients had excellent reperfusion. These patients were divided into two cohorts based on PT: ≤30 minutes (777 patients, 59.3%) and > 30 minutes (533 patients, 40.7%). Good functional outcome was observed in 658 patients (50.2%). The interaction term between FPS and PT was significant (p=0.018). Individuals with FPS in ≤30 minutes had 11.5% higher adjusted predicted probability of good outcome compared with those who required ≥2 passes (58.2% vs. 46.7%, p=0.001). However, there was no significant difference in the adjusted predicted probability of good outcome based on FPS in individuals with PT >30 minutes (p=0.763). This relationship appeared identical in models with PT treated as a continuous variable. Conclusion: In a large, real-world, multi-national dataset, we find that FPE is importantly modified by PT. The added clinical benefit of FPE is lost in longer procedures (>30 minutes). These data argue for a new metric for MT procedures, namely, FPE 30 , that better represents the ideal of fast, complete reperfusion with a single pass of a thrombectomy device.

For patients with locoregionally confined pancreatic ductal adenocarcinoma (PDAC), margin-negative surgical resection is the only known curative treatment; however, the majority of patients are not operable candidates at initial diagnosis. Among patients with resectable disease who undergo surgery alone, the 5-year survival remains poor. Adjuvant therapies, including systemic therapy or chemoradiation, are utilized as they improve locoregional control and overall survival. There has been increasing interest in the use of neoadjuvant therapy to obtain early control of occult metastatic disease, allow local tumor response to facilitate margin-negative resection, and provide a test of time and biology to assist with the selection of candidates most likely to benefit from radical surgical resection. However, limited guidance exists regarding the relative effectiveness of treatment options. In this systematic review, the American Radium Society multidisciplinary gastrointestinal expert panel convened to develop Appropriate Use Criteria evaluating the evidence regarding neoadjuvant treatment for patients with PDAC, including surgery, systemic therapy, and radiotherapy, in terms of oncologic outcomes and quality of life. The evidence was assessed using the Population, Intervention, Comparator, Outcome, and Study (PICOS) design framework and “Preferred Reporting Items for Systematic Reviews and Meta-analyses” 2020 methodology. Eligible studies included phases 2 to 3 trials, meta-analyses, and retrospective analyses published between January 1, 2012 and December 30, 2022 in the Ovid Medline database. A summary of recommendations based on the available literature is outlined to guide practitioners in the management of patients with PDAC.

Background: Minimal residual disease (MRD) is an established, prognostic indicator for patients with acute lymphoblastic leukemia (ALL), including Philadelphia chromosome-positive (Ph+) ALL. The objective of this study was to evaluate the association between MRD and long-term outcomes (event-free survival [EFS] and overall survival [OS]) in adult patients with Ph+ ALL receiving first-line therapy. Methods: A systematic literature review (SLR) was performed to identify eligible studies, including interventional and observational studies reporting survival outcomes by MRD status in adults ≥18 years of age with Ph+ ALL receiving first-line therapy. Key outcomes and data elements of interest were EFS, OS, and MRD or MRD-negative complete remission (CR) at end of induction (EOI). Aggregate study-level and individual patient data (IPD) meta-analyses were conducted. The IPD approach included a log-level MRD analysis to evaluate the concordance of deepening levels of molecular response with long-term EFS or OS in patients with CR and an analysis evaluating the utility of MRD-negative CR over CR alone. The analyses were conducted using frequentist and Bayesian approaches with fixed-effects and random-effects models. Kaplan-Meier method with log-rank tests was used for survival analysis. Where applicable, Cox regression method with and without adjustment for prognostic factors were applied. Results: The SLR identified 19 publications (18 unique studies), 10 (9 unique studies) of which had sufficient MRD and EFS/OS data. Nine studies (n=704) were included in the aggregate study-level analysis; 3 of the 9 studies (Phase II AP24534-11-001 [Jabbour et al. 2015], Phase II GIMEMAINCB 84344-201 [Martinelli et al. 2017], and Phase III GRAAPH-2005 RCT [Chalandon et al. 2015]) had IPD available. MRD was assessed by polymerase chain reaction in all 9 studies. Findings from the aggregate study-level meta-analysis demonstrated a significant long-term survival benefit (EFS and OS) in favor of patients with MRD-negative CR. This significant benefit was generally consistent across analysis types (base-case or sensitivity analyses), analytic models (fixed- or random-effects), and approaches (frequentist or Bayesian). Evidence from the IPD analysis, based on patients with CR, was mostly consistent with the aggregate study-level meta-analysis, supporting MRD-negative CR at the EOI as being predictive of EFS or OS. Log-level MRD analysis showed that patients who are in CR with deeper molecular response ( BCR::ABL1/ABL1 ≤0.01%) at EOI have significantly better long-term EFS and OS compared with patients with other levels of MRD (ie, BCR::ABL1/ABL1 &gt;0.01%). This significant long-term survival benefit was also demonstrated in patients with MRD-negative CR ( BCR::ABL1/ABL1 ≤0.01%) at EOI compared with patients who were MRD-positive ( BCR::ABL1/ABL1 &gt;0.01%) ( Table 1) or based on achievement of CR alone (regardless of BCR::ABL1/ABL1 values). Results from the IPD analysis standardized for outcome definition, with and without adjustment for prognostic factors (age, gender, white blood cell count at baseline, and stem cell transplant), were consistent with the findings from the log-level MRD analysis. The analysis showed a significant association between MRD-negative/MRD-negative CR status (ie, BCR::ABL1/ABL1 ≤0.01% threshold) at EOI with improved long-term EFS and OS. The results were significant for EFS in both the adjusted and unadjusted models. The OS results were significant only in the unadjusted model. Conclusions: These analyses indicate that a deeper molecular response at EOI results in better long-term EFS and OS; MRD-negative CR has a greater prognostic value than CR and is strongly associated with long-term EFS and OS in patients with Ph+ ALL. Acknowledgement: The authors acknowledge APHP, who provided the individualized patients data for the GRAAPH study.

Background: Ph-like ALL is a high-risk subset of B-lineage ALL that responds poorly to standard chemotherapy regimens. While allogeneic hematopoietic cell transplantation (HCT) is routinely recommended for patients with Ph-like ALL, large multicenter data addressing its role is limited. Here, we conducted a multicenter study to evaluate the role of HCT in adolescent and young adult (AYA) and adult patients (pts) with Ph-like ALL and compare their outcomes to pts with Ph-pos and Ph-neg (non-Ph-like) ALL. Methods: The study included pts (age ≥18) with B-lineage ALL who received HCT in first complete remission (CR1) at 3 academic centers (MD Anderson Cancer Center, City of Hope and Mayo Clinic) between 2006 and 2021. Pts were divided into 3 main subgroups: Ph-like, Ph-pos and Ph-neg ALL. Ph-like ALL cases were identified using cumulative data obtained by targeted RNA sequencing, conventional cytogenetics, FISH studies, whole genome chromosomal microarray and flow cytometry. Measurable residual disease (MRD) prior to HCT was measured using flow cytometry with a sensitivity of 0.01% for Ph-neg and Ph-like ALL, and with a PCR assay for BCR::ABL1 for Ph-pos ALL. MRD-negativity was defined as &lt;0.01%. Predictors of relapse were evaluated in univariate and multivariate analysis using Fine-Gray sub-distribution hazard models considering non-relapse mortality (NRM) as a competing risk. Results: 673 patients were identified, 83 (12.3%) had Ph-like ALL, of which 73% had CRLF2-alterations. The remaining patients were classified either as Ph-pos (N=271, 40.3%) or Ph-neg ALL (N=319, 47.4%). Patients with Ph-like ALL were younger (median age 40 years vs 48 and 46 years for Ph-pos and Ph-neg ALL, respectively, p=0.01), more likely to be of Hispanic ethnicity (69% vs 32% and 48% for Ph-pos and Ph-neg ALL respectively, p&lt;0.001). Patients with Ph-like ALL were also more likely to have induction failure (24% vs 2% and 11% for Ph-pos and Ph-neg ALL, respectively, p=0.001). A summary of pts characteristics for each subgroup can be found in Table 1. The median follow-up was 30, 52 and 48 months for patients with Ph-like, Ph-pos and Ph-neg ALL, respectively. In univariate analysis, 3-yr OS and PFS did not differ significantly (66% and 59% vs 59% and 54%, p=0.1) between patients with Ph-like and Ph-neg ALL, respectively. Similarly, the cumulative incidence of relapse was comparable between patients with Ph-like and Ph-neg ALL (22% vs 20%, respectively, p=0.7). In contrast, the 3-yr OS (75%, p&lt;0.001) and PFS (70%, p=0.001) were significantly higher and relapse rate significantly lower (12%, p=0.003) in pts with Ph-pos ALL compared with Ph-like or Ph-neg ALL (Figure 1). The inferior survival in patients with Ph-like and Ph-neg ALL was likely attributable to higher relapse rates (22% and 20% vs 12%, respectively, p=0.003) compared to Ph-pos ALL. Finally, the 3-yr NRM rate in patients with Ph-like ALL was comparable (20% vs 18% and 23%, respectively, p&gt;0.1) to Ph-pos and Ph-neg ALL. We confirmed that the relapse rate in patients with Ph-like ALL was comparable to the rate in pts with Ph-neg ALL (HR=1.02, 95% CI 0.6-1.8, p=0.9) on multivariate analysis (MVA). Ph-pos ALL was associated with a significantly lower relapse rate compared with Ph-neg ALL (HR=0.4, 95% CI 0.3-0.7, p&lt;0.001). MRD positivity prior to allo-HCT was the only additional significant predictor for relapse on MVA (HR=2.9, 95% CI 1.8-4.7, p&lt;0.001). Conclusions: HCT appears to overcome the poor prognosis of patients with Ph-like ALL. Despite higher induction failure rates, patients with Ph-like ALL undergoing HCT in CR1 had similar outcomes to other Ph-neg ALL subsets. The impact of effective salvage therapy leading to MRD-negativity in CR1 in this group is under investigation and will be reported. Further studies are needed to assess the impact of different Ph-like alterations on HCT outcomes. Outcomes for patients with Ph-pos ALL are significantly better than other groups, likely due to the use of TKIs pre- and post-HCT.

While the cure rate of pediatric acute lymphoblastic leukemia (ALL) now exceeds ~90% with contemporary combination chemotherapy, the prognosis for adults with ALL remains significantly inferior with long-term overall survival ranging from 50% to 70%. Recent studies have uncovered marked differences in ALL genomics between children and adults, with some high-risk subtypes becoming more prevalent with age. However, the underlying biology of age-related disparities in ALL is not fully understood, especially with regard to differences in leukemia sensitivity to chemotherapy. To address this knowledge gap, we performed ex vivo drug sensitivity profiling (i.e., pharmacotyping) of 21 anti-leukemia agents on primary B-ALL diagnostic samples from 767 pediatric (age, 0-18 years) and 309 adult (19-84 years) patients. Drug sensitivity was measured as LC 50: the concentration of drug required to kill 50% of the leukemia cells (PMID: 36604538). A total of 7,975 unique LC 50 values were experimentally determined. RNA-seq was used for subtype classification and gene expression analysis. Among 21 drugs, seven showed significant differences in overall LC 50 between children and adults ( P&lt;0.05 after Bonferroni correction): children displayed higher sensitivity to asparaginase, prednisolone, mercaptopurine, daunorubicin, and inotuzumab, while adults showed higher sensitivity to dasatinib and nelarabine. In multivariate models adjusting for 23 ALL molecular subtypes, only mercaptopurine remained significantly associated with age ( P=1.5×10 -5), suggesting that age-related differences in drug sensitivity can be primarily attributed to the variation in ALL subtypes between children and adults. For mercaptopurine, within KMT2A, CRLF2, and DUX4 subtypes, pediatric samples consistently showed a lower LC 50 than adults carrying the same genomic abnormality ( P=0.032, 0.0045, and 0.02, respectively). To explore intra-subtype heterogeneity, we performed unsupervised clustering using gene expression data for each of these three subtypes. Remarkably, within each of these subtypes, we identified two clusters with distinct transcriptomic profiles that were also largely segregated by age group, i.e., an adult-dominated cluster (C-a) and a pediatric-dominated cluster (C-p). In the KMT2A subtype, cases in C-a exhibited an over-representation of the KMT2A:: AFF1 fusion, and resistance to mercaptopurine ( P=0.029), prednisolone ( P=0.0039), vincristine ( P=0.046) and cytarabine ( P=0.0037). Within CRLF2 ALL, cases in C-a were associated with the presence of BCR:: ABL1-like signature and IGH:: CRLF2 rearrangements, and were more resistant to mercaptopurine ( P=0.0073) and prednisolone ( P=0.00036) compared to those in C-p. For DUX4 ALL, C-a was characterized by an under-representation of ERG deletions and resistance to mercaptopurine ( P=0.0056) and prednisolone ( P=0.0031), compared to C-p within DUX4. To explore the clinical relevance of this heterogeneity, we analyzed the in vivo treatment response of KMT2A (N=35), CRLF2 (N=59) and DUX4 (N=118) B-ALL enrolled in six frontline ALL trials. Compared to cases in C-p (usually drug-sensitive), those in C-a (usually drug-resistant) consistently had significantly poorer initial treatment responses as measured by persistent end-of-induction minimal residual disease (≥0.01%) in KMT2A (58% vs 9%; P=0.0063), CRLF2 (74% vs 41%; P=0.030), and DUX4 (66% vs 40%; P=0.0058) ALL. In conclusion, these studies have revealed important new insights into the pharmacogenomic basis of age-related differences in B-ALL treatment response. These results indicate that both inter- and intra-subtype heterogeneity contribute to inferior prognosis in adults with ALL, but also point to therapeutic opportunities to improve their outcomes.

Background: Obe-cel is an autologous chimeric antigen receptor (CAR) T cell product with a novel CD19 binding domain CAT conferring a fast antigen off-rate designed to mitigate safety concerns and improve persistence over approved CD19 CAR T therapies. Early results from the pivotal FELIX study Phase IIA cohort (N=94) were recently presented (Roddie C et al. J Clin Oncol 2023;41[16 Suppl]:7000). We report findings from a pooled analysis of all patients (pts) treated to date with obe-cel in the FELIX Phase Ib/II study (NCT04404660), with a focus on pts with low leukemia burden prior to obe-cel infusion. Methods: The FELIX study enrolled adults with R/R B-ALL at screening with either morphological disease ≥5% bone marrow (BM) blasts (Cohort A), or in ≥2 nd complete remission (CR)/CR with incomplete hematologic recovery (CRi) with measurable residual disease (MRD) (Cohort B), or with isolated extramedullary disease (EMD) (Cohort C). The Phase Ib part of the study enrolled Cohorts A and B; the Phase II part enrolled Cohorts A, B, and C. CAR T products were generated from leukapheresis material using an automated process. Pts received bridging therapy as needed and lymphodepletion with fludarabine (4 × 30mg/m 2) and cyclophosphamide (2 × 500mg/m 2). A target dose of 410 × 10 6 CAR T cells was infused as a split dose on Days 1 and 10 based on pre-lymphodepletion BM blast burden. The primary endpoint was overall remission rate (best response of CR/CRi by independent review). Secondary endpoints included duration of remission (DoR), MRD negative remission rate, safety, and CAR T expansion/persistence. This pooled analysis included data from pts treated with obe-cel across all cohorts in the Phase Ib/II parts of the study. Low leukemia burden was defined as morphological remission per investigator assessment (&lt;5% BM blasts without EMD) as measured at screening or at the start of lymphodepletion. Results: Between September 2020 and December 2022, 152 pts were enrolled and underwent leukapheresis. As of 16 March 2023, obe-cel was successfully administered to 126/152 (83%) pts (Phase Ib: Cohort A n=13, B n=3; Phase II: Cohort A n=94, B n=9, C n=7). Baseline characteristics at screening (n=126): median age 46.5 (range 20-81) yrs; Philadelphia positive B-ALL 27%; median 2 (range 1-6) prior lines of therapy; prior blinatumomab/inotuzumab 42%/32%; median BM blast burden 37% (range 0-100) including 23% pts with EMD; prior allogeneic stem cell transplant 44%. At a median follow up of 11.0 (range 0.9-30.6) months, the CR/CRi rate was 77% (95/124 response evaluable pts) with CR rate 57% (71/124). Among MRD evaluable responders, 96% achieved MRD negative status by central flow cytometry analysis. Median DoR was not reached at the current follow up. Low rates of Grade (Gr) ≥3 cytokine release syndrome (CRS; 2.4%) and/or Gr ≥3 immune effector cell associated neurotoxicity syndrome (ICANS; 7.1%) were observed. CAR T expansion was similar across the Phase Ib/II cohorts and CAR T persistence was ongoing in the majority of responders at the current follow up. Preliminary data indicate favorable efficacy and safety in pts with low leukemia burden prior to obe-cel infusion. Among 12 pts with MRD at screening (Cohort B), two pts were not evaluable and 9/10 evaluable pts achieved CR/CRi, with 100% achieving MRD negative status by central flow cytometry analysis post obe-cel. Median DoR was not reached at the current follow up. In this subset, no Gr ≥3 CRS was observed; one pt had Gr ≥3 ICANS. In a subset of 28 pts (across all cohorts) in morphological remission at the time of lymphodepletion, 24/27 (89%) response evaluable pts achieved CR/CRi and 100% of MRD evaluable responders achieved MRD negative CR/CRi by central flow cytometry analysis post obe-cel. Median DoR was not reached at the current follow up. In this subset, no pts experienced Gr ≥3 CRS/ICANS. Conclusions:This pooled analysis of data from all pts treated to date in the FELIX study demonstrates high rates of CR/CRi after obe-cel treatment, durable responses (median DoR not reached), and a favorable safety profile. Preliminary data suggest better outcomes in pts with low leukemia burden at screening/lymphodepletion, with higher rates of deep MRD negative complete remission, median DoR not reached at the current follow up, no Gr ≥3 CRS and one Gr ≥3 ICANS. These data support further exploration of CAR T therapy earlier in the treatment algorithm for adults with ALL.

Background As the number of thrombectomy passes increases during endovascular therapy (EVT) for acute stroke, neurointerventionalists must weigh the risks of potential complications against the risk of failing to recanalize the affected vessel. Thus, we investigated the effectiveness and safety of EVT for patients with acute stroke in which ≥5 EVT passes were performed. Methods This retrospective cohort study from January 2013 to December 2022 included 31 thrombectomy‐capable centers. Patients in whom ≥5 EVT passes were made were included in the analysis. The patients with successful recanalization defined as modified Thrombolysis in Cerebral Infarction ≥2b at 5, 6, 7, or more passes were compared with unsuccessful recanalization. We also compared procedure time, separated by 30 minutes. Primary outcome was a favorable 90‐day outcome (modified Rankin scale score of 0–2). Secondary outcomes were intracranial hemorrhage and death. Results A total of 407 patients met the inclusion criteria, of which 175 were women (43.1%); the mean age was 67.3 years. In 265 (65.1%) patients, successful recanalization was achieved: 134 patients with 5 passes, 67 patients with 6 passes, and 64 with ≥7 passes. Intravenous recombinant tissue plasminogen activator administration was more common in the unsuccessful recanalization group (successful recanalization with 5, 6, and ≥7 EVT passes and unsuccessful recanalization: 35.3%, 30.3%, 18.8%, and 45.4%, respectively). Successful recanalization with 5, 6, and ≥7 EVT passes was associated with favorable outcome compared with unsuccessful recanalization group (adjusted odds ratio successful recanalization with 5, 6, and ≥7 EVT passes to unsuccessful recanalization [95% CIs]: 8.29 [2.13–32.3]; 14.0 [3.27–60.3]; and 5.26 [1.12–24.8], respectively). However, symptomatic intracranial hemorrhage was not significantly different between the groups. Regarding procedure time, favorable outcome was not significantly different in each group, while symptomatic intracranial hemorrhage occurred more frequently in the 60 to 89 minutes group compared with the <30 minutes group (adjusted odds ratio, 60–89 minutes group to <30 minutes group [95% CI]: 5.86 [1.09–31.6]). Conclusion These findings suggest that a benefit in outcome persists for recanalization, without significant increase in complications. In addition, there was no significant difference in favorable outcomes among procedure time.