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Abstract Background: Chemotherapy-induced cardiomyopathy (CIC) is a serious, and often irreversible complication in patients treated for hematologic malignancies. While therapies for hematologic malignancies continue to evolve, data on trends in in-hospital mortality among patients with concurrent hematologic malignancies and CIC are limited, and disparities by race and sex remain poorly characterized. This study examines national trends and demographic disparities in in-hospital mortality among patients with hematologic malignancies who developed CIC. Methods: The United States (U.S) National Inpatient Sample (NIS) from 2016 to 2020 was queried for patients diagnosed with malignant hematologic and lymphoid neoplasms who also developed CIC. Hematologic malignancies were identified using ICD-10 codes C81–C96, which include: C81 for Hodgkin lymphoma; C82–C86 for non-Hodgkin lymphomas; C88 for malignant immunoproliferative diseases (e.g., Waldenström macroglobulinemia, heavy chain disease); C90–C95 for leukemias of lymphoid, myeloid, monocytic, mixed, and unspecified cell types; and C96 for other or unspecified malignant neoplasms of lymphoid, hematopoietic, and related tissue. CIC was identified using ICD-10 code I42.7. The study was exempt from institutional review board approval as the NIS database contains deidentified patient information. Multivariable regression analysis was performed to determine the odds of in-hospital mortality among patients with hematologic malignancies who developed CIC. Multivariable logistic regression followed by marginal effects was used to plot yearly trends in in-hospital mortality. All the outcomes were adjusted for gender, race, Charlson comorbidity index and hospital characteristics. P < 0.05 was used to determine statistical significance. The analysis was performed on STATA 16 software. Results: The study identified a total of 3,021,434 hospitalizations with hematologic malignancies, of which 11,115 (0.004%) had secondary diagnosis of CIC (mean age = 56.5 years, 52.5% males). Among 11,115 patients with hematologic malignancies who developed CIC, 740 (6.6%) patients died during the hospitalization. Multivariable logistic regression followed by marginal effects estimated a decrease in adjusted in-hospital mortality trend from 6.5% in 2016 to 4.3% in 2020. However, this decreasing mortality trend was not statistically significant after adjusting for gender, race, Charlson comorbidity index, and hospital characteristics (OR: 0.93; 95% CI: 0.83 – 1.05; trend p = 0.260). In-hospital mortality did not differ significantly between male vs. female patients with hematologic malignancies who developed CIC (OR: 1.02; 95% CI: 0.72 – 1.43; p = 0.921). There was no difference in overall in-hospital mortality of patients of White (reference) vs. Black (OR: 1.12; 95% CI: 0.72 – 1.76, p = 0.61) or Hispanic (OR: 0.63; 95% CI: 0.32 – 1.25, p = 0.18) race. However, males of the Black race demonstrated a lower in-hospital mortality vs. males of the White race (OR: 0.26; 95% CI: 0.09 – 0.77, p = 0.01). In addition, females of the Black race showed a higher in-hospital mortality vs. females of the White race (OR: 2.43; 95% CI: 1.40 – 4.25, p <0.01). Conclusions: In patients with hematologic malignancies who developed CIC, overall in-hospital mortality did not differ significantly by race alone. However, on sex-based stratification, Black males had lower in-hospital mortality compared to White males, while Black females had higher mortality than White females. These differences highlight potential race–sex disparities in outcomes that warrant further investigation.

Abstract Introduction: Nucleophosmin 1 mutations (NPM1-m) drive leukemogenesis in approximately 30% of acute myeloid leukemia (AML) cases. Ziftomenib is a potent, highly selective, oral, investigational menin inhibitor that has demonstrated clinical activity as both monotherapy and in combination for adults with NPM1-m or lysine methyltransferase 2A-rearranged (KMT2A-r) AML. KOMET-007 (NCT05735184) is an ongoing, open-label, dose-escalation (phase 1a) and expansion (phase 1b) study of ziftomenib in combination with standard chemotherapies in NPM1-m or KMT2A-r AML. Here we present phase 1b safety and clinical activity in patients with newly diagnosed NPM1-m AML who received the recommended phase 2 dose (RP2D) of ziftomenib 600 mg in combination with venetoclax and azacitidine (Ven/Aza). Methods: Adults (≥18 years) with newly diagnosed NPM1-m AML who were not eligible for intensive chemotherapy were enrolled in phase 1b and received ziftomenib 600 mg once daily plus standard doses of Ven/Aza. Ziftomenib was orally administered once daily continuously from Cycle 1 Day 8 onward. Phase 1b primary endpoints were adverse events (AEs) and complete remission (CR) per ELN 2022. Secondary endpoints included composite CR (CRc; defined as CR with full, partial, or incomplete hematologic recovery), overall response, and duration of response. Local measurable residual disease (MRD) was assessed by next-generation sequencing, RT-qPCR, and multiparameter flow cytometry. Results: As of June 25, 2025, 39 patients with newly diagnosed NPM1-m AML were enrolled and treated with ziftomenib 600 mg once daily plus Ven/Aza in phase 1b. Median age was 75 years (range 53–93), 54% were female, 46% had ECOG PS 0–1; 12 (31%) had FLT3 co-mutations and 9 (23%) had IDH co-mutations. Median duration of follow-up was 16.3 weeks (range 1.6–41.1). Twenty-nine patients (74%) had grade ≥3 treatment-emergent AEs, most commonly (≥20% of patients) decreased neutrophil count (31%) and decreased platelet count (23%). Grade ≥3 ziftomenib-related AEs occurred in 14 patients (36%), most commonly decreased neutrophil count (15%) and decreased platelet count (13%). No ziftomenib treatment discontinuations occurred due to AEs. Differentiation syndrome occurred in 1 (3%) patient (grade 2), which successfully resolved with protocol-specified mitigation. One patient (3%) had investigator-assessed ziftomenib-associated QTc prolongation (grade 3); however, there were concomitant significant electrolyte abnormalities and event resolved with electrolyte repletion. At time of data cutoff, 31 NPM1-m patients were response-evaluable (≥1 response assessment or death). CRc rate was 84% (26/31) after a median time to first CRc of 3.5 weeks (range 2.4–9.4), with local MRD-negativity rates among tested CRc responders of 54% (13/24) after a median time to first MRD-negativity of 8.4 weeks (range 2.9–17.4). CR rate was 58% (18/31) and overall response rate was 94% (29/31), with responses and MRD-negativity rates continuing to evolve. During continuous ziftomenib administration in patients who achieved CRc, median time to neutrophil recovery (≥1×109/L) was 36 days, and median time to platelet recovery (≥100×109/L) was 28 days. The median duration of response and median overall survival were not reached as of the data cutoff, at a median follow-up of 16.3 weeks. The study is ongoing, with 81% (25/31) of NPM1-m patients still on-study and 77% (24/31) still on ziftomenib treatment. Updated safety and clinical activity results will be presented.Conclusions: In the ongoing KOMET-007 study, ziftomenib RP2D of 600 mg once daily combined with Ven/Aza was well tolerated and demonstrated robust clinical activity in patients with newly diagnosed NPM1-m AML, including 84% CRc after a median of 3.5 weeks and 54% CRc MRD-negativity after a median of 8.4 weeks. Low rates of ziftomenib-related cytopenia and no additional myelosuppression were observed with this combination. One case each of differentiation syndrome (grade 2) and investigator-assessed QTc (grade 3) were successfully resolved. Taken together, these data support the RP2D determination and advancement of this ziftomenib-based combination in the KOMET-017 (NCT07007312) randomized phase 3 study in patients with newly diagnosed NPM1-m AML.

Abstract Background In patients with myelofibrosis (MF) undergoing allogeneic hematopoietic cell transplantation (allo-HCT), graft-versus-host disease (GVHD) prophylaxis has traditionally included a calcineurin inhibitor (CNI) plus methotrexate (MTX). We conducted a retrospective study comparing the safety and efficacy of post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis to CNI-based regimens. Methods This study was approved by the Mayo Clinic IRB. Patients with myelofibrosis who underwent allo-HCT after 2016 at Mayo Clinic in Arizona and Florida were included. Categorical variables were compared using Chi-square or Fisher's exact tests. Overall survival (OS) was defined from transplant to death, and progression-free survival (PFS) from transplant to relapse or death. OS and PFS were estimated using Kaplan-Meier methods; univariate differences were assessed with log-rank tests. The cumulative incidence of acute and chronic GVHD and time to neutrophil and platelet engraftment were analyzed using competing risk models, with death as a competing event; differences were tested using Gray's test. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs). Results A total of 110 patients were included. 53 patients received PTCy-based prophylaxis (43 PTCy/Tac/MMF, 1 PTCy/CSA/MMF, 9 PTCy/Siro/MMF), while 57 received non-PTCy regimens (54 Tac/MTX +/- 39 T-cell depletion, 2 CSA/MMF, 1 Tac/MMF). Median age at transplant was 63 (range: PTCy 40-76; others 38-74) years in both groups; 59 were male (58.5% PTCy vs 49.1% others). Median Karnofsky Performance Status (KPS) and HCT–Comorbidity Index (HCT-CI) in patients receiving PTCy vs non-PTCy were 90 vs 80 and 1 vs 3, respectively. Conditioning intensity was similar: 22.6% myeloablative vs 21.7%, and 77.4% reduced-intensity vs 76.7% in PTCy and non-PTCy, respectively (p=1.000). Stem cell source was peripheral blood in all patients except one in the non-PTCy group who received bone marrow. 58 patients had primary MF (54.7% PTCy vs 50.9% others), and 52 had secondary MF (45.3% PTCy vs 49.1% others), including essential thrombocythemia (28.3% PTCy vs 31.6% others), polycythemia vera (17.0% vs 15.8%), and MPN-NOS (0% vs 1.8%). Median follow-up was 26.2 months (95% CI: 20.7-52.7) in the PTCy and 60.6 months (95% CI: 53.1-70.6) in the non-PTCy cohort. CD3 and CD33 donor chimerism ≥95% at day +100 was 66.7% and 86.7% in PTCy vs 63.6% and 92.7% in others, respectively (p=0.50); day +100 driver molecular mutations were present in 32.1% of PTCy and 32.0% of others (p>0.99). Rates of acute GVHD grades ≥2 and ≥3 were not statistically significant, in the PTCy group (37.7% vs 49.1% p=0.229 and 17.0% vs 22.8% p=0.445, respectively). Chronic GVHD (any grade) occurred in 42.3% of PTCy vs 38.2% of others (p=0.664), while moderate-to-severe cGVHD was lower with PTCy (21.2% vs 27.3% p=0.461). Platelet engraftment was significantly delayed in the PTCy group (median 33 vs 21 days, p=0.030). Median time to neutrophil engraftment was also delayed in the PTCy group (20 vs 17 days, adjusted p=0.025). Age-adjusted HR for time to platelet engraftment was 0.60 (95% CI: 0.41–0.90; p=0.014), and for neutrophil engraftment 0.65 (95% CI: 0.44–0.95; p=0.025), indicating significantly delayed hematopoietic recovery with PTCy. Graft failure occurred in 9.4% vs 5.3% (p = 0.48); primary 7.5% vs 3.5%, secondary 1.9% vs 1.8% in PTCy vs non-PTCy groups, respectively. Relapse or progression occurred in 11.3% of PTCy vs 17.5% of others (p=0.355); four patients in the non-PTCy group progressed to AML post-transplant, versus none in the PTCy group (p=0.119). 1-year TRM was 22.6% in the PTCy group and 14.0% in the non-PTCy group, p = 0.324. Median OS was 72.8 months in the PTCy group (95% CI: 49.9 months, upper limit not estimable [NE]) and 93.4 months in the non-PTCy group (95% CI: 48.5 months, upper limit NE), although the difference was not statistically significant (p=0.739). After adjusting for age and HCT-CI, there were no significant differences in PFS (adjusted HR 1.37; 95% CI: 0.73–2.56; p=0.331) or OS (adjusted HR 1.27; 95% CI: 0.64–2.51; p=0.498). Conclusions In myelofibrosis patients undergoing allo-HCT, PTCy-based GVHD prophylaxis showed similar rates of grade ≥2 acute and moderate-severe chronic GVHD compared to non-PTCy regimens. Engraftment was significantly delayed, while OS and PFS were comparable. PTCy appears to be a safe and viable alternative to CNI-based prophylaxis.

Abstract Introduction Survival following allogeneic hematopoietic cell transplantation (allo-HCT) has improved over the last several decades. Implementation of reduced-intensity conditioning and improvement in graft selection, graft vs. host disease (GVHD) prophylaxis and treatment, and infection disease management, among others, have contributed to reducing non-relapse mortality (NRM). The use of post-transplant cyclophosphamide (PTCy) for GVHD prophylaxis, in particular, has been associated with reduced incidence of acute and chronic GVHD in both HLA-matched related and matched unrelated donor allografts. In this study, we aim to determine prognostic factors for NRM (including early NRM defined as within 100 days post-transplantation), disease-related mortality (DRM), and overall survival (OS) in a large cohort of patients following allo-HCT. Methods Patients who received consecutive allo-HCT at our institution from 2009-2023 were included. Clinical data were collected from retrospective reviews of the electronic medical records. Patient- and transplant-related variables were compared between patients who died and those who were alive at 100 days post allo-HCT. Univariate and multivariate Cox proportional hazard models were used to identify prognostic associations between risk factors and OS. Kaplan-Meier method was used to evaluate OS. Log-rank test was used to compare OS between groups. Statistical significance was set to < 0.05. Results A total of 536 patients (male=285, 53%) were included. Median age at time of allo-HCT was 59 (range, 19-75) years. Most patients were White/Caucasian (n=232, 86%). The most common diagnoses included acute myeloid leukemia (AML) (n=110, 41%), myelodysplastic syndrome (n=52, 19.2%), myelofibrosis (n=23, 9%), B-cell acute lymphoblastic leukemia (B-ALL) (n=22, 8.1%), non-Hodgkin lymphoma (n=21, 8%), and chronic myeloid leukemia (n=10, 4%). The median follow-up for survivors was 4.2 (range, 1.1-14.4) years. A total of 80 (14.9%) patients died within 100 days with most deaths attributed to NRM (n=61, 76%). Specific causes of death included infection/sepsis in 22 (27.5%) patients, GVHD in 10 (12.5%), respiratory failure in 9 (11.2%), multiorgan failure in 5 (6.3%), graft failure in 5 (6.3%), and other causes in 10 (12.5%). Progressive disease was the cause of death in 19 (23.8%) patients. Male gender (HR=1.92; p= 0.006), remission status other than CR1 or CR2 for acute leukemia patients (HR=8.44; p<0.0001), non- PTCy strategies (HR=2.4; p= 0.0006), and earlier year of transplantation (HR=1.12; p=< 0.001) were associated with increased risk of mortality at 100 days on univariate analysis. Only use of TBI (HR=2.56, p=0.048) and earlier year of transplantation (HR=1.2; p=0.001) were associated with increased risk of DRM at 100 days post-allografting on univariate analysis. Pertaining to risk of NRM at 100 days, male gender (HR=1.89; p=0.02), diagnosis other than acute leukemia (HR=2.27; p=0.004), non-PTCy strategies (HR=2.44; p=0.003), and earlier year of transplantation (HR=1.1; p=0.004) were adversely associated with NRM. On multivariate analysis, only earlier year of transplantation was found to be associated with increased risk of DRM at 100 days (HR 1.15; p=0.049). Male gender (HR=1.78; p=0.035), diagnosis other than acute leukemia (HR=2.38; p=0.003), and non-PTCy strategies (HR=2.2; p=0.032), were associated with increased risk of NRM at 100 days. Conclusion Non-relapse mortality (NRM) accounted for most deaths within the first 100 days of allo-HCT, primarily due to infection/sepsis and GVHD. Factors associated with increased NRM included male gender and diagnoses other than acute leukemia. Significantly, post-transplantation cyclophosphamide (PTCy) was the only treatment strategy modification that decreased 100-day NRM and improved survival, independent of the transplantation year.

Importance Treatment for cognitive dysfunction due to postacute sequelae of long COVID (ie, symptoms of fatigue, malaise, weakness, confusion that persist beyond 12 weeks after an initial COVID infection) remains a significant unmet need. Objective To test evidence-based rehabilitation strategies for improving cognitive symptoms in persons with long COVID. Design, Setting, and Participants This was a 5-arm, multicenter, randomized clinical trial of 3 remotely delivered interventions conducted between August 17, 2023, and June 10, 2024. The study took place at 22 trial sites and included the screening of individuals with cognitive long COVID. Interventions Participants were randomized to 1 of 5 arms: adaptive computerized cognitive training (BrainHQ [Posit Science]), cognitive-behavioral rehabilitation involving both group and individual counseling sessions (PASC-Cognitive Recovery [PASC-CoRE]) paired with BrainHQ, and transcranial direct current stimulation (tDCS) paired with BrainHQ. Two comparator arms were included as follows: unstructured computer puzzles and games (active comparator) and sham tDCS paired with BrainHQ. The interventions occurred 5 times per week over 10 weeks. Main Outcomes and Measures Cognitive and behavioral in-person assessments were performed at baseline, midintervention, at the end of intervention, and 3 months after the end of the intervention. The primary outcome measure was the modified Everyday Cognition Scale 2 (ECog2) completed at the end of the intervention compared to the baseline visit based on participant self-report looking back over the prior 7 days. Results A total of 378 individuals were screened, from which there were 328 participants (median [IQR] age, 48.0 [37.0-58.0] years; 241 female [73.5%]; race: 15 Asian [4.6%], 47 Black [14.3%], and 235 White [71.6%]; ethnicity: 52 Hispanic [15.9%]). None of the 3 active interventions demonstrated benefits on the modified ECog2 in the intention-to-treat population by the end of the intervention period. The adjusted differences in mean change were 0.0 (95% CI, −0.2 to 0.2) for BrainHQ vs active comparator, 0.1 (95% CI, −0.1 to 0.3) for PASC-CoRE + BrainHQ vs active comparator, 0.0 (95% CI, −0.2 to 0.2) for tDCS-active + BrainHQ vs tDCS-sham + BrainHQ, and 0.1 (95% CI, −0.1 to 0.3) for PASC-CoRE + BrainHQ vs BrainHQ alone. Secondary participant-reported outcomes and neuropsychological tests showed no differential benefits for any treatment arm. All 5 arms demonstrated some improvements over time on the modified ECog2 and on secondary outcomes. There were no serious adverse events attributable to the interventions. Conclusions and Relevance This phase 2 randomized clinical trial failed to demonstrate differential benefits for online cognitive training, a structured cognitive rehabilitation program, and tDCS for cognitive long COVID. Trial Registration ClinicalTrials.gov Identifier: NCT05965739 .

Background: Ultrasound-guided percutaneous fasciotomy and debridement (USPFD) is a minimally invasive treatment for patients with plantar fasciopathy refractory to conservative management. Previous studies have shown clinical improvement with USPFD, but pain relief and patient satisfaction have not been demonstrated beyond 2 years. Methods: This retrospective case series included patients who underwent USPFD at a quaternary academic medical center between April 2013 and January 2018, with refractory plantar fasciopathy and at least 4 years’ follow-up. Patient outcomes were assessed through electronic surveys and telephone interviews. Primary outcome measures included mean changes in visual analog scale pain (VAS-Pain) scores and patient satisfaction via Likert scale. Secondary measures included VAS-Pain with the first 5 steps, VAS-Pain during daily weightbearing, and procedural complications. Results: Seventy unique procedures were identified among 62 patients. Follow-up data were obtained from 51 of 62 patients (82%) who responded to surveys or phone calls. This corresponded to 58 of 70 procedures (83%) at a mean postprocedure follow-up of 6.6 ± 1.4 years. Patients had a mean duration of symptoms of 2.1 ± 3.0 years prior to the procedure. Baseline VAS-Pain was 6.8 ± 2.2 and final follow-up VAS-Pain was 0.7 ± 1.1. At the last follow-up, patient-reported VAS-Pain with first 5 steps was 0.9 ± 1.6 and VAS-Pain with weightbearing through the day was 1.3 ± 1.8. Overall, 91% (53/58) of the procedures were considered successful, where patients responded they were “satisfied” or “very satisfied” and 52 of 58 (90%) procedural responses indicated that based on the outcome, they would recommend the procedure to others. Final follow-up VAS-Pain, VAS-first 5 steps, and VAS-weightbearing, were all improved in the success vs failure groups ( P ≤ .002). No complications were reported. Conclusion: USPFD was associated with high patient satisfaction and durable pain relief for chronic plantar fasciopathy at an average follow-up of 6.6 ± 1.4 years.

Abstract The incidence of venous thromboembolism (VTE) in patients with acute lymphoblastic leukemia (ALL) receiving asparaginase-based induction is high despite primary thromboprophylaxis. Our aim was to derive and externally validate a VTE risk prediction model in patients with ALL receiving asparaginase-based induction. We conducted a multicenter retrospective cohort study of patients (aged ≥18 years) with newly diagnosed ALL receiving asparaginase-based induction. The derivation and external validation cohorts included 306 and 94 patients, respectively. Primary outcome was VTE at any site. A cause-specific Cox proportional hazards model stratified by thromboprophylaxis and center was performed to identify VTE risk factors in the derivation cohort. A risk prediction model for VTE at 30 days was derived using variables with P value < .05 in the multivariable model and was tested in the validation cohort. VTE risk factors on multivariable analysis in the derivation cohort included D-dimer ≥1 μg fibrinogen equivalent unit per mL (hazard ratio [HR], 2.64; 95% confidence interval [CI], 1.07-6.5) and hemoglobin (HR for each 1 g/dL increment, 1.19; 95% CI, 1.06-1.34) at ALL diagnosis. A VTE risk score based on these variables distinguished between a 4% (95% CI, 0.72-12) and 20% (95% CI, 14-27) 30-day cumulative incidence of VTE in the derivation cohort, with similar findings in the validation cohort (area under the curve, 0.56). The negative predictive value for VTE at 30 days was 96% and 93% in the derivation and validation cohorts, respectively, and the positive predictive value was 20% in both. We derived and validated a model using D-dimer and hemoglobin, which stratifies VTE risk in patients with ALL receiving asparaginase-based induction.

Purpose: To determine the factors associated with compliance with recommended intravitreal injections (IVIs) for retinal diseases among out-of-pocket, insured, and fully subsidized (non-paying) patients. Methods: This retrospective observational hospital-based study included patients recommended for IVI in at least one eye between November 2011 and May 2022. Three cohorts of patients were assessed: out-of-pocket payers, insured, and those fully subsidized (non-paying) by the hospital. The main outcome measure was the compliance rate, defined as the proportion of patients receiving an injection after one was recommended. The impact on the visual outcome in each cohort was a secondary outcome. Results: Overall, 50,408 IVI were recommended for at least one eye and were included in the analyses. Male patients were more common (66.72%), and the mean age was 55.36 ± 16.39 years. The overall compliance rate with the first recommended injection was 51.37%, which increased and eventually stabilized with subsequent recommendations to approximately 80% (range: 77.48%–82.93%). Insured patients had a higher compliance rate with the first recommendation compared to the non-insured (100% vs. 49.84%; P < 0.000 01 ), and non-paying patients had a higher compliance rate after the first recommendation compared to paying patients (62.51% vs. 48.66%; P < 0.000 01 ). Patients with insurance achieved a better visual outcome at the last follow-up compared to other cohorts. Conclusion: Insured patients have a much higher compliance rate with recommended IVIs compared to out-of-pocket or non-paying patients. The high non-compliance rate among non-paying patients suggests that factors other than the direct cost of the injections may impact compliance with recommended treatment.