Ilyas, Usman

e24088 Background: Chemotherapy-induced nausea and vomiting (CINV) significantly affects treatment tolerance and quality of life. ASCO guidelines recommend a NK-1 receptor antagonist with a 5-HT3 receptor antagonist and corticosteroid for patients receiving highly emetogenic chemotherapy (HEC). Olanzapine has emerged as an alternative antiemetic, with evidence suggesting noninferiority in triple regimens. Given its favorable cost profile, we performed a pooled analysis comparing olanzapine- versus aprepitant-based triple antiemetic regimens for CINV prevention. Methods: This PRISMA-compliant review was prospectively registered in PROSPERO (CRD420261284983). Five databases were systematically searched to identify studies comparing olanzapine (OLZ) versus aprepitant (APR) based triple antiemetic regimens. The primary endpoint was complete response (CR) for prophylaxis of chemotherapy-induced nausea and vomiting (CINV) in adult patients receiving HEC. Statistical analyses were performed in R (version 2025.05.0+496; Posit). Results: 13 studies were included in the final synthesis, comprising 1,557 patients (OLZ: n = 779; APR: n = 788). CR was comparable between groups (RR 1.02, 95% CI 0.95–1.09; I² = 55.8%). Exclusion of Mehta et al. (2017) reduced heterogeneity to zero (I² = 0%). In the acute phase ( < 24 h), CR was also similar between OLZ and APR (RR 1.09, 95% CI 0.98–1.20; I² = 82.7%); however, OLZ demonstrated superior CR in the 10-mg dose subgroup (RR 1.08, 95% CI 1.03–1.14; I² = 74%). For delayed-phase CR (24-120 h), the pooled effect estimate was RR 1.11 (95% CI 0.98–1.27; I² = 84.3%). Control of nausea was significantly improved in the OLZ group compared with APR (RR 1.19, 95% CI 1.01–1.40; I² = 72.8%), particularly in anthracycline–cyclophosphamide–based regimens (RR 1.30, 95% CI 1.09–1.54; I² = 62.9%) and the 10-mg OLZ dose subgroup (RR 1.22, 95% CI 1.01–1.49; I² = 75.2%). Nausea control was also superior in both the acute phase (RR 1.13, 95% CI 1.01–1.27; I² = 76.5%) and the delayed phase (RR 1.31, 95% CI 1.05–1.65; I² = 93.3%). Control of vomiting was comparable between OLZ and APR (RR 0.99, 95% CI 0.92–1.07; I² = 0%), with no significant differences observed in the acute ( < 24 h) phase (RR 1.03, 95% CI 0.97–1.10; I² = 49%) or the delayed (24–120 h) phase (RR 1.00, 95% CI 0.97–1.04; I² = 0%). Conclusions: OLZ-based triple antiemetic regimens provide comparable CR and vomiting control to APR, with superior nausea control, particularly in anthracycline–cyclophosphamide regimens and at the 10-mg dose.

e18609 Background: Anemia is a frequent complication of myelofibrosis (MF) and is embedded in widely used prognostic systems, yet contemporary real-world estimates of its association with long-term survival and leukemic transformation remain limited. We evaluated the impact of baseline anemia (hemoglobin [Hb] <10 g/dL) on overall survival (OS) and risk of transformation to acute myeloid leukemia (AML) in adults with MF. Methods: We performed a retrospective cohort study using the TriNetX Research Network, identifying adults (≥18 years) with myelofibrosis and stratifying them by anemia status at index (Hb <10 g/dL). Patients with the outcome of interest prior to each analytic window were excluded. To minimize confounding, cohorts were 1:1 propensity score–matched using nearest-neighbor matching with a caliper of 0.1 pooled standard deviations of the logit of the propensity score, adjusting for demographic factors, comorbidities, iron supplementation, leukocyte count, and platelet count. Balance was assessed using standardized mean differences <0.1. The primary outcome was all-cause mortality and the secondary outcome was transformation to AML, assessed at 1, 3, and 5 years. Risk estimates were calculated, and survival analyses were performed using Kaplan–Meier curves and Cox proportional hazards models, with statistical significance defined as a two-sided p<0.05. Results: After matching, 18,504 patients with MF were identified, of which 51.6% were females and 48.3% were males. The mortality rate in patients with anemia was higher than in those without at years 1, 3, and 5: 21.4%, 33.2%, and 39%, respectively, versus 5.4%, 12%, and 16.9%, respectively. The prevalence of transformation to AML was also higher in patients with anemia at 3.7%, 4.9%, and 5.3% at years 1, 3, and 5, respectively, versus 0.1%, 0.3%, and 0.4% in patients without anemia at those same time points. The HR for mortality in MF patients with anemia when compared to those without anemia at years 1, 3, 5 was statistically significant at 4.57 (95% CI 4.14-5.05, log-rank p<0.01), 3.51 (95% CI 3.28-3.76, log-rank p<0.01), and 3.04 (95% CI 2.87-3.23, log-rank p<0.01) respectively. The HR for transformation to AML in patients with MF with anemia versus those without anemia was statistically significant at years 1, 3 and 5, with HRs of 34.96 (95% CI 19.17-63.75, log-rank p<0.01) 20.75 (95% CI 13.97-30.83, log-rank p<0.01) and 17.07 (95% CI 12.11-24.07, log-rank p<0.01), respectively. Conclusions: In this large, propensity-matched real-world EHR analysis, baseline Hb <10 g/dL was associated with substantially worse OS and a markedly higher risk of AML transformation through 5 years. These findings support anemia as a pragmatic risk marker to inform risk-adapted monitoring, supportive care, and therapeutic decision-making in MF.

e18608 Background: Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) that is characterized by bone marrow fibrosis and inefficient hematopoiesis, leading to extramedullary hematopoiesis. Leukocytosis, a common disease manifestation and a minor criterion for the diagnosis of MF, has been associated with poorer clinical outcomes. This study evaluates the long term impact of leukocytosis on clinical outcomes at different time points in the real-world population of patients with MF. Methods: We conducted a retrospective cohort study using de-identified EHR data from the TriNetX Global Federated Health Research Network. Adults (≥18 years) with myelofibrosis were identified using ICD-10 and ICD-O-3 codes and stratified into leukocytosis (WBC ≥25.0 ×10³/µL; L+) and non-leukocytosis (L−) cohorts at the index diagnosis. Patients with prior or current hematopoietic stem cell transplantation were excluded. Cohorts were propensity score–matched 1:1 for demographics, comorbidities, and baseline laboratory values. Outcomes at 1, 3, and 5 years included all-cause mortality, pulmonary embolism, venous thromboembolism, and transformation to acute myeloid leukemia, with hazard ratios estimated using Cox proportional hazards models. Results: After matching, 13237 patients with MF were identified, of whom 52.12% were male, and 47.8% were female. The mean age in L+ and L- was 66.5 +/- 16.6 years and 68.1 +/- 15.5 years, respectively. The mean hemoglobin in L+ was 10.9+/- 2.8 g/dL, and in L- was 12.9+/- 2.3 g/dL. The mean platelet count in L+ was 303.4+/- 294.9 and in L- was 239.5+/- 151.4 ×10³/µL. HR for all-cause mortality in L+ when compared to L- at years 1, 3, and 5 were statistically significant at 4.079 (95% CI 3.691-4.508), 3.215 (95% CI 2.982-3.466), and 2.787 (95% CI 2.608-2.978), respectively, with log-rank p < 0.01. The HR for PE in L+ when compared to L- was statistically significant at years 1, 3, and 5 at 2.014 (95% CI 1.455-2.787), 1.883 (95% CI 1.451-2.787) and 1.659 (95% CI 1.318-2.088) with log-rank p<0.01. HR for VTE in L+ when compared to L- was statistically significant at years 1, 3, and 5 at 2.501 (95% CI 1.937-3 .229), 1.802 (95% CI 1.491-2.178), and 1.561 (95% CI 1.32-1.847) with log-rank p<0.01. Risk of transformation to AML in L+ when compared to L- at years 1, 3, and 5 was significant with HRs being 9.806 (95% CI 6.575-14.627), 8.823 (95% CI 6.334-12.29), 9.371 (95% CI 6.813-12.891) with log-rank p<0.01. Conclusions: In this large real-world, propensity-matched cohort, leukocytosis in myelofibrosis was associated with significantly higher risks of all-cause mortality, thromboembolic events, and transformation to acute myeloid leukemia across 1-, 3-, and 5-year time points. These findings underscore leukocytosis as a powerful adverse prognostic marker in MF and highlight the need for closer surveillance and risk-adapted therapeutic strategies in this high-risk population.

e18605 Background: Patients with myelofibrosis (MF), especially those with marked leukocytosis, face increased risk for thrombotic complications such as pulmonary embolism (PE) and venous thromboembolism (VTE). Hydroxyurea (HU) is often used to control blood counts. However, evidence for HU reducing thrombotic events in MF is limited, and contemporary real-world data on its impact in MF populations with significant leukocytosis remain sparse. Methods: We conducted a retrospective cohort study using the TriNetX research network. Adult patients with MF and leukocytosis (white blood cell count ≥25×10⁹/L) were identified. Patients with prior allogeneic hematopoietic stem cell transplantation were excluded. HU-exposed patients were compared with non-exposed patients using 1:1 propensity score matching. Matching criteria included age, sex, race, comorbidities, and baseline laboratory values when available. The study included 3,590 patients (1,795 per cohort). Primary outcomes were time to PE and VTE at 1, 3, and 5 years. Hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox proportional hazards models. Results: In the propensity-matched cohort, HU exposure was not associated with a statistically significant reduction in thrombotic events. For PE, hazard ratios were numerically higher in the HU-exposed group at 1 year (1.5% vs 1.0%; HR 1.40, 95% CI 0.76–2.56; p=0.278) and 3 years (2.2% vs 1.8%; HR 1.29, 95% CI 0.80–2.08; p=0.289), with a modest increase observed at 5 years (2.8% vs 1.9%; HR 1.57, 95% CI 1.01–2.45; p=0.04). For VTE, no statistically significant differences were observed between HU-exposed and non-exposed patients at any time point (1 year: HR 0.95, 95% CI 0.63–1.44; p=0.821; 3 years: HR 0.97, 95% CI 0.69–1.36; p=0.85; 5 years: HR 1.14, 95% CI 0.84–1.57; p=0.40). Overall, PE and VTE event rates remained low and comparable between cohorts. Conclusions: In this large real-world cohort of patients with myelofibrosis and significant leukocytosis, hydroxyurea exposure was not associated with a statistically significant reduction in thrombotic events, including PE or VTE, over short- or long-term follow-up. Thrombotic event rates were low and generally comparable between hydroxyurea-exposed and non-exposed patients, with no consistent pattern suggesting a protective effect of cytoreductive therapy. Although a modest increase in PE risk was observed at 5 years, this finding was isolated and lacked a consistent temporal pattern, limiting its clinical interpretability. These findings suggest that the role of hydroxyurea in modifying thrombotic risk among MF patients with leukocytosis remains uncertain and highlight the need for individualized treatment decisions and further studies to better define its impact on thrombotic outcomes in this population.

Abstract Background Thrombotic Thrombocytopenic Purpura (TTP) is a rare, typically acquired disorder due to an immune-mediated deficiency of ADAMTS13, a metalloprotease responsible for cleaving large multimers of von Willebrand Factor (vWF). In the absence of ADAMTS13 activity, ultra-large vWF multimers accumulate, promoting widespread platelet aggregation and microvascular thrombosis. This consumptive cascade leads to thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological symptoms, and rarely renal dysfunction. Although therapeutic plasma exchange (TPE) has long been the cornerstone of TTP treatment, the FDA approved Caplacizumab as a first-line treatment for TTP in 2019. This drug is a bivalent single-domain antibody that binds to the A1 domain of vWF and prevents its interaction with platelets, thus effectively interrupting the pathogenic cascade, which is associated with a risk of bleeding. Methods We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, comprising data from 152 healthcare organizations. Adults (≥18 years) with a diagnosis of TTP who received Caplacizumab plus TPE were compared to patients with TTP who received TPE alone. 1:1 propensity score matching (PSM) was performed to balance characteristics between cohorts. The primary outcomes assessed were all-cause mortality and major bleeding events over a period of 1 month. Results A total of 4084 patients with TTP were identified, of whom 356 received caplacizumab with TPE and 3728 received TPE. After PSM, 2 balanced cohorts were created: C+P (Caplacizumab + TPE), P only (TPE), each comprising 356 patients. The average age in C+P and P only, after PSM, was 50.4 +/- 16.2 and 50.8 +/- 16.2 years, respectively. Females formed 65.7% of both C+P and P only, and males accounted for 28.4% and 28.7% of C+P and P only, respectively. 2.8% patients in C+P and 7.06% patients in P only had all-cause mortality at the end of 1 month. One-month all-cause mortality was significantly lower in C+P (2.8%) compared to P only (7.06%), with an odds ratio (OR) of 0.385 (95% CI 0.182 to 0.814, p=0.010). Upon assessment of bleeding outcomes, no statistically significant risk difference was noted between the 2 groups, with the odds ratio being 0.974 (95% CI 0.399 to 2.379, p=0.954). Conclusion Our large database study suggests that the addition of caplacizumab to standard TPE therapy is associated with a reduction in one-month all-cause mortality in patients with TTP, without a corresponding increase in major bleeding. However, given the lack of granular clinical data, such as contraindications to caplacizumab use, it is possible that patients who received TPE alone were inherently at a higher risk. As such, while these findings support the potential benefit of early caplacizumab use, they should be interpreted with caution and warrant prospective validation to confirm causality and assess long-term outcomes.

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&gt;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.