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Abstract Introduction TP53MT are associated with poor outcomes in MDS, especially in the context of biallelic MT. We have previously reported on outcomes of pts with HR-MDS with TP53MT who received HMA in the VALIDATE dataset (Kewan T et al, ASH 2023). Here we provide expanded analyses focusing on outcomes post allo-HCT, and we explore the prognostic significance of different classification methods for biallelic TP53MT. Methods The VALIDATE database includes 4,732 pts with MDS who received HMA-based frontline therapy from 32 international centers in 9 countries. For this study, only pts with HR-MDS with molecular data at time of diagnosis were included. Biallelic TP53MT status was assessed using three classification schemes: WHO 2022, ICC 2022, and a VAF-based Cleveland Clinic Foundation (CCF) method.1TP53 copy neutral loss of heterozygosity (CN-LOH) was evaluable in 386 pts (118 had TP53MT). Treatment responses were evaluated using IWG 2023 criteria (Zeidan A et al, Blood 2023). Composite complete remission (cCR) was defined as CR+CRbi+CRuni+CRh+CRequivalent. We calculated OS from time of HMA initiation to date of death or last follow up. Unsupervised clustering (MOSAIC framework) was applied to identify molecular subgroups within the TP53MT cohort. The study was funded by an independent grant from Abbvie. Results A total of 1,485 pts were included. Median age was 69 years (IQR: 62–76), with 66% male pts. Median bone marrow blast was 7%, and 28% had a complex karyotype. Treatment regimens included azacitidine (68%), decitabine (15%), HMA/Venetoclax (8%), and other HMA combinations (9%); 34% underwent allo-HCT. Overall, 392 (26%) had TP53MT with 430 TP53 mutations (missense: 316; truncating: 89). Biallelic TP53MT % varied by classification: 72% (WHO), 84% (ICC), and 85% (CCF). Compared to TP53 wild-type (TP53WT) pts, pts with TP53MT had worse OS (median: 11.5 vs. 23.9 months [mo], p< 0.001), were younger (68 vs. 70 years, p=0.039), and had lower counts at diagnosis. Complex karyotype (81% vs. 14%) and chromosomal abnormalities were more frequent in TP53MT pts. Pts with TP53MT also had fewer co-mutations in other genes. Response to HMA was evaluable in 1,094 pts: cCR and CR were 32% and 13%, respectively. TP53MT pts had higher cCR (39% vs. 29%, p=0.001) than TP53WT, but similar CR rates (16% vs. 12%, p=0.093). According to WHO 2022, biallelic TP53MT had higher CR rates than monoallelic TP53MT (18% vs. 8%, p=0.03), but similar cCR. ICC and CCF classifications did not differentiate response rates. Median OS did not differ by TP53MT allelic status using WHO or ICC definitions. However, using the CCF method, pts with biallelic TP53MT had shorter OS than monoallelic TP53MT (10.4 vs. 17.2 mo, p=0.038). In multivariable models adjusted for age, gender, and allo-HCT, only the CCF-defined biallelic TP53MT group had significantly worse OS (HR: 1.6; 95% CI: 1.1–2.4). TP53MT pts undergoing allo-HCT had improved OS regardless of allelic status. Median OS for TP53MT pts with allo-HCT was 18.9 vs. 9.2 mo without all-HCT. This benefit was observed across WHO, ICC, and CCF classifications. However, a TP53MT VAF ≥19% predicted worse OS even post allo-HCT (14.6 vs. 47.1 mo, p<0.001). At 1 year, the survival rate was 78% (95%CI: 69-89%) in TP53MT pts who underwent allo-HCT and had cCR vs. 68% (95%CI: 55-84%) in pts who did not have cCR. However, 1 year survival rate was significantly higher for pts with TP53MT who did not have allo-HCT and achieved cCR (60%, 95%CI: 48-76%) vs. no cCR (26%, 95%CI: 20-35%). Unsupervised clustering of 335 TP53MT pts identified 9 molecular clusters (MCs). MC2, characterized by low TP53MT VAF (median 17%), fewer co-mutations, and frequent del17p, was associated with significantly improved OS (17.9 mo) and predicted favorable outcome (HR for death: 0.6; 95% CI: 0.4–0.8). Other clusters were enriched for adverse features (e.g., high VAF, multi-hit TP53MT).Conclusions The CCF method appears to best classify biallelic TP53MT pts with worse survival in the absence of accurate assessment of LOH status. Treatment response per IWG 2023 for TP53MT pts was associated with OS only in non-transplanted pts. Allo-HCT improved survival across TP53MT subsets, but TP53 VAF ≥19% at diagnosis remained a strong negative prognostic factor. Integrative clustering revealed a less aggresive molecular subset among TP53MT pts, suggesting refined risk stratification may guide therapy in this high-risk population. Ref: 1.Bahaj et al. J Hematol Oncol 2023.

Abstract Introduction: Marrow complete remission (mCR) in 2006 IWG criteria for MDS (Cheson B et al, Blood 2006) reflects achieving bone marrow (BM) blast percentage below 5% but is frequently not associated with meaningful count recovery. While mCR + hematologic improvement (HI) does reflect wide ranges of count improvement or transfusion reductions, HI is difficult to measure accurately in routine clinical practice. The 2023 International Working Group (IWG) response criteria (Zeidan A et al, Blood 2023) eliminated the mCR category without meaningful count recovery and reclassified mCR associated with meaningful count recovery into specific “less-than-CR” categories. Still, many clinical trials continue to use mCR as a secondary efficacy endpoint or as a part of overall response rate (ORR). Within the icMDS VALIDATE database, we assessed the association of mCR with OS in hypomethylating agent (HMA)-treated higher risk (HR)-MDS patients among both (1) transplanted and (2) non-transplanted patients. Methods We included patients with HR-MDS (defined as IPSS ≥1.5 and/or IPSS-R >3.5) who received HMA-based therapies from the international icMDS VALIDATE dataset. We evaluated the best response by IWG 2006 criteria into CR, mCR, or no CR/mCR. We then reclassified patients with mCR per IWG 2023 criteria into either (A) having achieved a composite CR (cCR) defined as CR + CR equivalent (CRequ) + CR with bilineage count recovery (CRbi) + CR with unilineage count recovery (CRuni) + CR with partial hematologic recovery (CRh) or (B) not having achieved cCR (no cCR). OS was calculated from time of HMA initiation to date of death or last follow-up by using 6-month landmark analyses. We used Kaplan-Meier methods to estimate OS, and the Log-rank test to compare OS. VALIDATE is supported by an independent grant from AbbVie. Results A total of1049 patients met eligibility.Median age of patients was 69 (range 21-95), 64% were men. While 61% received azacitidine, 17% received decitabine, and 22% received HMA-based combination therapy. In total, 37% underwent subsequent allogenic stem cell transplantation (allo-HCT). Based on IWG 2006 criteria, 17%, 33%, and 50% achieved CR, mCR, and no CR/mCR as their best response, respectively. Patients achieving CR had superior median OS (25 months, 95% CI: 21-34 months) compared to those with mCR (16 months, 95% CI: 13-18 months; p=0.038) and no CR/mCR (15 months, 95% CI: 12-17 months; p=0.001). In patients who received a subsequent allo-HCT, the median OS for patients with mCR (30 months, 95% CI: 21-54 months; 1 year OS: 71%, 2 year OS: 55%) did not significantly differ compared to patients with CR (59 months, 95% CI: 25 months-not reached, p=0.80; 1 year OS: 73%, 2 year OS 62%) and patients with no CR/mCR (32 months, 95% CI: 21-45 months, p=0.46; 1 year OS: 69%, 2 year OS 54%). In contrast, in patients treated with HMA therapy alone without subsequent allo-HCT, median OS for patients with mCR (11 months, 95% CI: 9-15 months; 1 year OS: 46%, 2 year OS: 23%) did not significantly differ compared to patients with no CR/mCR (11 months, 95% CI: 9-14 months, p=0.85; 1 year OS: 47%, 2 year OS: 22%) but was significantly shorter compared to patients with CR (20 months, 95% CI: 17-28 months, p<0.001; 1 year OS: 69%, 2 year OS: 46%). Patients with mCR by IWG 2006 (N=347) were reclassified per IWG 2023 into having either achieved a cCR (N=219, 63%) or no cCR (N=128, 37%). Specifically, patients with mCR were reclassified per IWG 2023 into CR (4.9%), CRequ (0.6%), CRbi (26.8%), CRuni (29.4%), CRh (1.4%), PR (0%), HI (10%), no response (21.9%) and PD (4.9%). Patients with mCR who were reclassified into cCR had an improved median OS (16 months, 95% CI: 15-26 months; 1 year OS: 62%; 2 year OS: 43%) compared to patients reclassified into no cCR per IWG 2023 (13 months, 95% CI: 11-17 months, p=0.023; 1 year OS: 52%; 2 year OS: 31%). Conclusions Using the large icMDS VALIDATE dataset, we found that achievement of mCR by 2006 IWG criteria was not associated with improved OS compared to patients who did not achieve CR/mCR. Reclassification of mCR using IWG 2023 highlights the heterogeneity within the mCR group and suggests that IWG 2023 criteria stratifies outcomes in patients previously labeled as mCR by IWG 2006. IWG 2023 should be the standard used for ORR assessment in all future clinical trials involving patients with HR-MDS.

Abstract Introduction: CD19-directed CAR T-cell (CAR-T) therapy has substantially improved clinical outcomes for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). However, notable toxicities are associated with CAR-T, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Variable practice patterns have emerged regarding the use of CRS/ICANS prophylaxis (ppx) via corticosteroids and/or other pharmacologic agents, but the utility of these approaches on reducing CRS or ICANS following CAR-T in B-ALL remains unknown. Thus, we utilized the Real-World Outcomes Collaborative for CAR T in ALL (ROCCA) database to evaluate associations between ppx and the development and severity of CRS or ICANS following brexucabtagene autoleucel (brexu-cel) for B-ALL. Methods: Adult patients (pts) who received standard-of-care brexu-cel for relapsed/refractory B-ALL across 40+ US centers were included. Primary endpoints were the incidence of CRS and ICANS within 28 days of CAR-T infusion. Secondary endpoints included timing of CRS and ICANS onset, progression-free survival (PFS) and overall survival (OS). Univariable and multivariable logistic regression evaluated associations between ppx and incidence of CRS/ICANS; KM and log-rank methods were used for survival analyses. Results: A total of 378 pts were included: 53 pts (14.0%) received CRS/ICANS ppx and 325 (86.0%) received no ppx. Ppx agents included steroids only (26.4%), steroid and anakinra (52.8%), anakinra only (15.1%), and steroid and tocilizumab (5.7%). Pts in the ppx group had a higher proportion of Hispanic pts (64% vs 34%), Ph-like (36% vs 19%) and a lower proportion had 0-5% bone marrow blasts at apheresis (38% vs 53%). The ppx and no ppx groups were similar in age, prior therapies, CAR-T indication, and marrow blasts >50%. Cumulative incidence of any grade (gr) CRS was 94% with ppx and 86% with no ppx (p=0.025), of any gr ICANS was 53% with ppx and 51% with no ppx (0= 0.85). Cumulative incidence of gr 3-4 CRS was 9% in the ppx group and 10% in the no ppx group (p=1.00), of gr 3-4 ICANS was 26% in the ppx group and 29% in the no ppx group (p=0.71). Median time to onset for any gr CRS or any gr ICANS was identical in the ppx and no ppx cohorts (CRS: 5 days, range ppx 1-9 days, no ppx 0-14 days; ICANS: 7 days, ppx 1-20 days, no ppx 0-16 days). Univariate logistic regression analyses showed no significant association between ppx and the incidence of gr 2-4 CRS (OR 1.34, 95% CI: 0.75-2.40, p=0.326) or gr 3-4 ICANS (OR 0.88, 95% CI: 0.46-1.70, p=0.708). Multivariate analysis adjusting for ethnicity, leukemia genetic sub-type, and pre-apheresis disease burden similarly found no significant associations between ppx and gr 2-4 CRS (adjusted OR 1.06, 95% CI: 0.55-2.01, p=0.870) or gr 3-4 ICANS (OR 1.23, 95% CI: 0.59-2.55, p=0.584). When comparing steroid-only ppx (N=14) to steroid combinations or other drug ppx (N=39), there was no significant differences in gr 2-4 CRS (57% vs 44%, p=0.345) or gr 3-4 ICANS (43% vs 21%, p=0.115). Comparing cumulative incidence of dexamethasone (dex) exposure, pts in the ppx group had numerically greater dex exposure than pts in the no ppx group, with median (range) dosing of 182 mg (10-1386mg) and 100mg (1-4000mg), respectively. Finally, we found no significant differences in PFS or OS based on ppx. Median PFS was 9.6 months in the ppx group vs 13.3 months in the no ppx group (p=0.646) and median OS was 17.2 months in the ppx group vs 34.4 months in the no ppx group (p=0.170). Conclusions: In this large cohort of adult patients with R/R ALL receiving brexu-cel CAR-T therapy, prophylaxis intended to prevent CRS/ICANS was ineffective at reducing CRS/ICANS incidence, time to onset, or overall steroid exposure. Furthermore, PFS and OS were comparable between patients who received prophylaxis and those who did not. In the absence of prospective trials in B-ALL, these data suggest that current strategies of CRS/ICANS prophylaxis has limited benefit.

Abstract Introduction: Epcoritamab (epco) and glofitamab (glofit) are bispecific antibodies (BsAbs) approved for the treatment of patients (pts) with relapsed or refractory (r/r) large B-cell lymphomas (LBCLs). Their use is associated with relatively high response rates, with some patients experiencing prolonged remission. It is unclear whether continuous treatment beyond 12 months for pts in remission is beneficial, as continued immunosuppression may result in additional toxicity. We sought to report the outcomes of pts with prolonged remission and survival following BsAb administration. Methods: We performed a multicenter retrospective study including 21 US centers evaluating pts with r/r LBCLs receiving commercially available epco or glofit between 2023 and 2025. Baseline characteristics and outcomes were extracted from medical records. Efficacy and survival outcomes were assessed by site investigators and included overall response rate (ORR), complete and partial response (CR, PR) rates. Pts who responded to BsAbs and had ≥365 days of follow-up from initiation of BsAb treatment were included in the analysis. Results: As of May 15, 2025, a total of 312 pts with r/r LBCLs were treated with BsAbs (epco n=193, glofit n=119) with a median age of 66 years (interquartile range [IQR] 59-73) at BsAb start. Most were male (64.5%), had advanced stage disease (77.4%) and had ECOG performance status of ≤1 (93.3%) at BsAb start. Of 207 pts who had initiated treatment with BsAb ≥12 months prior to data cutoff, we identified 31 pts (15.0%) who had a response to BsAbs (19 epco, 12 glofit) and were alive without progression at 12-months post-BsAb initiation and included them in this landmark analysis. Of the cohort of 19 pts treated with epco, 6 discontinued due to reasons other than disease progression including CAR-T cell therapy (n=2), secondary malignancy (n=2), allogeneic transplant (n=1), or other reasons (n=1). Thirteen of 19 pts received ≥12 months of epco treatment, and, with a median follow-up of 16 months from the start of BsAb, 12 of 13 pts continued receiving epco beyond 12 months with one pt discontinuing after 12 months (observed for an additional 41 days prior to censoring). Of the cohort of 12 pts treated with glofit, 8 pts were observed after completing all planned therapy and 4 patients underwent allogeneic transplant. Among all 31 BsAb-treated patients alive and in remission at 12 months, at the time of data cutoff, 5 pts (12.9%) had progressed (2 previously treated with epco and 3 with glofit). Three of the 4 pts who underwent allogeneic transplant after prior glofit treatment experienced disease relapse. A total of 24 pts (77.4%) were alive at the time of last follow-up, with the causes of death being disease progression (n=1), secondary malignancy (n=1), infection (n=1), and unknown cause (n=4). Conclusions: In this large cohort of r/r LBCL pts treated with BsAbs monotherapy in the standard of care setting, a relatively small proportion of pts (15%) achieve the 12 month PFS landmark. In the absence of robust evidence for what constitutes best practice, different strategies are employed, including continuation of BsAb, observation as well as consolidation with allogeneic transplant or CAR T-cell therapy. Additional follow-up will be reported to help guide clinical decision making regarding the optimal management strategy for this high risk pt population.

Abstract Introduction: Brexu-cel is a highly effective treatment for R/R B-ALL, with complete responses achieved in 71% of patients (pts) treated in the pivotal ZUMA-3 trial. Patients with B-ALL with high-risk (HR) genetics are known to have inferior outcomes with chemotherapy, but little is known about the influence of HR ALL genetics on responses to chimeric antigen receptor (CAR)-T in adults. In this study, we assessed the impact of HR ALL genetics on outcomes in a large cohort of adult patients treated with brexu-cel for R/R Philadelphia chromosome (Ph)-negative B-ALL. Methods: Patient characteristics and outcomes were obtained from the Real-World Outcomes Collaborative of CAR-T in Adult ALL (ROCCA) database which includes data from 40 U.S. centers. NCCN guidelines (NCCN Guidelines in Oncology, ALL v2.2025) were used to define HR B-ALL genetics; lack of HR genetics was defined as standard-risk (SR). The primary outcome was event-free survival (EFS), defined as lack of response, disease progression, or death from any cause. Secondary outcomes were overall survival (OS), relapse free survival (RFS) and response rates including complete response (CR), CR incomplete count recovery (CRi), measurable residual disease negative CR (MRD-) by flow or NGS and progressive disease (PD). Multivariable models were adjusted for age, pre-infusion blast percentage, prior allo-HCT, and post CAR-T allo-HCT (modeled as a time-varying covariate). Results: The cohort included 286 pts: 169 with HR and 117 with SR B-ALL. The HR cohort included TP53m (n=24, 14%), KMT2Ar (n=16, 9%), CRLF2r (n=65, 39%) and other HR genetics such as JAK2 and other Ph-like, IKZF1, complex cytogenetics (n=64, 38%). Relative to SR pts, HR pts were more commonly Hispanic (50% vs 28%). HR and SR pts had similar disease burden pre-apheresis (>5% blasts: 58% vs 53%), prior blinatumomab (60% vs 58%), prior inotuzumab (42% vs 46%), and prior allo HCT (27% vs 37%). The presence of CNS disease (11% HR vs 12% SR) and extramedullary disease (EMD, 22% HR vs 29% SR) at apheresis was also similar. CR/CRi was achieved in 90.5% of evaluable HR pts (n=147) and 90.2% of evaluable SR pts (n=102); MRD- rates were also similar between HR and SR pts at 78.9% and 78.2% respectively. In unadjusted analyses, EFS did not significantly differ between HR pts (median 9.6 mos; 1-yr: 46%, 95% CI 38%-54%) and SR pts (median 11.6 mos; 1-yr: 48%, 95% CI 38%- 58%). Median RFS (HR: 12.2 mos, SR: 13.3 mos) and median OS (HR: 22.4 mos, SR: 21.0 mos) were also similar. Multivariable models demonstrated no significant associations between HR B-ALL and EFS (HR 1.09, 95% CI 0.73-1.63), RFS (HR 1.13, 95% CI 0.71-1.80), or OS (HR 0.96, 95% CI 0.62- 1.48) relative to SR ALL. 28% of HR patients and 21% of SR patients underwent consolidative allo-HCT. Among the HR subgroup, CR/CRi rate was lowest in KMT2Ar (71%) relative to TP53m (95%), CRLF2r (95%), and other HR genetics (89%). The median EFS was lowest in KMT2Ar (4.1 mos), followed by TP53m (6.9 mos), CRLF2r (11.6 mos), and other HR (11.1 mos). Median OS was also lowest in KMT2Ar (6.8 mos) vs 22.4 mos in TP53m and not reached in CRLF2r or other HR. PD was highest in KMT2Ar pts (29%), as compared to 11% HR other, 10% SR, and 5% TP53 and CRLF2r. The rate of relapse among those that achieved CR across the groups was similar and ranged between 28% -40%. Rates of CD19 negative relapse were similar between all subgroups (13%-15%), however 21% of KMT2A pts underwent myeloid transformation as compared 0% for TP53 and CRLF2 pts, and 2% among other HR and SR pts. 25% of KMT2Ar patients underwent consolidative allo-HCT as compared to 32% CRLF2 pts, 29% TP53 pts, 25% other HR pts and 21% SR pts. Multivariable models evaluating the different genomic subgroups demonstrated that relative to SR B-ALL, only KMT2Ar was associated with inferior OS (HR 3.17, 95% CI 1.53-6.58, p=0020). No associations were seen between HR subgroups and EFS. Conclusion: To our knowledge, this analysis represents the largest examination of adult B-ALL recipients of CAR-T assessed by genomic risk group. We found that response rates and survival outcomes following brexu-cel were similar among HR and SR B-ALL pts, including pts with TP53m and CRLF2r. However, pts with KMT2Ar had lower response rates and dismal EFS and OS, with higher rates of PD and myeloid transformation at relapse, suggesting that alternative strategies are necessary to improve outcomes for patients with R/R KMT2Ar B-ALL.

OBJECTIVE Objective values on procedural risk are essential to facilitate informed consent and optimize clinical decision-making in patients with unruptured intracranial aneurysms (UIAs). While robust heuristics, such as the PHASES (population, hypertension, age, size of aneurysm, earlier subarachnoid hemorrhage, and site of aneurysm) score, are established for predicting rupture risk, contemporary and granular benchmarks for procedural safety remain scarce. The multinational Prediction of Adverse Events After Microsurgery for Intracranial Unruptured Aneurysms (PRAEMIUM) study aims to comprehensively characterize contemporary adverse event rates following microsurgical treatment at high-volume expert centers, stratified by aneurysm location, morphology, and complexity factors to better inform individual risk/benefit analyses. METHODS A cohort study among 20 participating expert centers from 9 countries was established. Patients treated microsurgically for UIAs were included. The authors describe the epidemiology of treated patients and UIAs and a comprehensive adverse event profile using 3 outcomes measured at hospital discharge: 1) poor neurological outcome (modified Rankin Scale score ≥ 3), 2) new sensorimotor neurological deficits, and 3) all-cause adverse events (Clavien-Dindo grade ≥ 1). Subgroup reports were given for aneurysm location, morphology, and complexity factors (prior aneurysm treatment, calcifications, complex angioanatomy involving critical branch vessels or perforators, and thrombosis). The authors purposely chose discharge as the time point to capture early postoperative risks and complications in patients with asymptomatic UIAs, for whom preserving neurological function is paramount. RESULTS The cohort included 3705 patients (mean age 56 [SD 12] years, 28% male). Overall, at discharge 13.9% of patients (95% CI 12.8%–15.0%) had poor neurological functional outcomes, 14.4% (95% CI 13.3%–15.5%) had new sensorimotor deficits, and 24.1% (95% CI 22.8%–25.5%) experienced all-cause adverse events. Poor neurological outcomes ranged from 8.5% (M1 aneurysms) to 37.4% (posterior circulation aneurysms), neurological deficits from 9.3% (distal anterior cerebral artery [ACA] aneurysms) to 34.2% (posterior circulation aneurysms), and all-cause adverse events from 21.2% (distal ACA aneurysms) to 31.3% (posterior circulation aneurysms). Dissecting and fusiform aneurysms showed notably high rates of poor neurological outcomes (22.0%–33.3%), new deficits (25.4%–26.7%), and adverse events (26.7%–37.0%). Complexity factors significantly influenced outcomes, with prior treatment (22.9%, 19.7%, and 30.1%), calcification (16.3%, 18.1%, and 30.5%), complex angioanatomy (13.1%, 15.9%, and 26.9%), and thrombosis (19.6%, 23.9%, and 39.6%) notably increasing the risks for poor neurological outcomes, deficits, and adverse events, respectively. CONCLUSIONS This large international cohort provides contemporary benchmarks for microsurgical treatment of UIAs, emphasizing variability in outcomes based on aneurysm location, morphology, and complexity. The presented granular and quotable adverse event rates support informed patient counseling and individualized risk/benefit assessments in comparable high-volume centers.

ABSTRACT Background Symptom management in myeloproliferative neoplasms (MPN) remains challenging despite advancements in disease‐directed therapies. This study assessed the impact of demographic, clinical, laboratory and treatment‐related variables on total symptom scores (TSS) and individual symptom scores in patients with polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF). Methods A cohort of 553 patients (PV: 200; ET: 190; MF: 163) was identified through a retrospective chart review. Symptom scores, demographic information and clinical variables were captured at the time of the first TSS assessment. Laboratory results within 1 month and treatment information within 90 days prior to the symptom assessment were captured. Univariable linear regression, followed by multivariable regression analyses using a robust variance estimator were performed, with a p value < 0.05 indicating a significant association. Results MF patients experienced the highest symptom burden and fatigue was the most reported symptom across all MPN subtypes. In PV, depression ( β : 10.53; p = 0.001) was associated with a higher TSS whereas older age (−0.17; 0.01) and higher hemoglobin (−1.24; 0.003) were associated with a lower TSS. In ET, depression ( β : 14.19; p < 0.001) was associated with a higher TSS, whereas in MF, depression (12.28; < 0.001) and higher WBC count (0.22; 0.02) were associated with a higher TSS. Depression and non‐White race in PV, depression in ET, and depression, low hemoglobin, and higher WBC count in MF were associated with multiple symptoms. Conclusions Integrating depression screening and management and optimizing hematologic parameters alongside disease‐directed therapy is crucial to improving patient outcomes.

In 2023, the American Congress of Rehabilitation Medicine Brain Injury Interdisciplinary Special Interest Group (ACRM BI-ISIG) Mild Traumatic Brain Injury (TBI) Task Force published updated diagnostic criteria for mild TBI. These criteria were developed in collaboration with a panel of 32 subject matter experts in mild TBI using the Delphi method. The 2023 ACRM diagnostic criteria marked the first update since 1993, incorporating three decades of research advancements in our understanding of mild TBI. To facilitate the consistent use of the new diagnostic criteria, the ACRM BI-ISIG Mild TBI Task Force initiated a special project in September 2023 to develop a structured interview to apply the ACRM diagnostic criteria for mild TBI in clinical and research settings. The purpose of this article is to describe the development of the ACRM Structured TBI Interview and the accompanying documents. The ACRM Structured TBI Interview was developed in four phases: (1) initial development of a draft interview by two project leads, (2) review and revision over three rounds by 17 members of the ACRM BI-ISIG Mild TBI Task Force, (3) external review by 19 subject matter experts in mild TBI, and (4) field testing of the ACRM Structured TBI Interview by 11 interviewers who completed 25 diagnostic interviews. In addition to the ACRM Structured TBI Interview, three other documents were developed to help facilitate the administration of the interview (Administration Guide) and to apply the diagnostic criteria (Diagnostic Coding Form and Diagnostic Flow Diagram). A Short Form was also developed for use in contexts where administering the full structured interview is not feasible due to time constraints.

Glioblastoma (GBM) is an aggressive brain tumor that often progresses despite resection and treatment. Timely and continuous assessment of GBM progression is critical to expedite secondary surgery or enrollment in clinical trials. However, current progression detection requires costly and specialized MRI examinations, which, in the absence of new symptoms or signs, are usually scheduled every 2–3 months. Here, we hypothesized that changes in daily activity are associated with GBM growth and disease progression. We found that wheel-running activity in GBM-bearing mice declined as tumors grew and preceded weight loss and circadian breakdown by over a week. Temozolomide treatment in the morning, but not evening, significantly reduced tumor size and restored daily locomotion in mice. In a pilot study of 6 patients with GBM wearing an actigraphy watch, wrist movement provided a feasible and continuous longitudinal indicator of daily activity with 1-minute resolution. After tumor resection and radiation, daily activity declined in 2 patients 19 and 55 days before detection of progression by MRI but did not change for the 4 patients with stable disease. These results suggest that daily activity tracking using wearable devices may serve as a real-time indicator and potential monitoring tool for GBM progression and treatment efficacy.