Citations

Abstract Gentically driven classical hematological disorders have variable prevelance in the general population, sickle cell disease (SCD) being the most common at 30 per 100,000 people, hemophilia (hem) 12 per 100,000 people for hemophilia A, 4 per 100,000 people for hemophilia B, and thalassemia (thal) at 18 per 100,000 people, with regional and racial-ethnic variation across US. There has been a dramatic change in the therapeutic landscape for these diseases in the past decade. Several new drugs and biological therapies including gene therapies have been approved for each of these disorders. Clinicians utilize different information sources to assimilate this rapid influx of knowledge into their practice; in the era of social media, the readership is not limited to original publications. As research visibility influences clinical adoption and patient awareness, it is vital to understand the modalities of engagement of gene therapy studies by clinicians and patients. An altmetric score is a simple and effective way of understanding engagement with research across platforms. It. measures digital attention received by research output, allowing us to gauge the social impact of an article. We sought to compare the impact and scientific dissemination of publications of gene therapy trials in these 3 diseases by capturing the number of traditional citations and Altmetric assessment score. Methods: A PubMed search was conducted for gene therapy trials in SCD, Hem and Thal between 2015 to 2025 and citations were captured using metrics from Google Scholar. The Altmetric assessment score for each article was determined using www.altmetric.com which includes any mention by news outlets, blogs, Twitter (X), Facebook, and Mendeley reader counts. Descriptive statistics are reported for the number of citations as well as the Altmetric assessment score in each of the disease categories. Median and range were reported due to the skewed distribution of the data. Comparison across groups for significance was done using the Kruskal-Wallis test. Results: The number of qualifying studies for SCD (n=7) were lower than hem (n=21) and thal (n=12). Median PubMed citations were highest for SCD (147, range 4-436), followed by hem (26, range 0-828) and thal (42, range 0-801), though the difference was not statistically significant (p=0.4) Altmetric scores demonstrated differences that approached statistical significance with p=0.08: SCD had the highest median (422, range 4-770), driven by exceptional Twitter engagement, while hem and thal medians were 20 (range 0-2038) and 49 (range 0-825) respectively. Twitter/X was the leading social platforms for all diseases. Scholarly interest measured by Mendeley readers was also highest for SCD (median 195, range 11-542), with thal and hem medians at 50 (range 0-773) and 64 (range 8-646) respectively. Conclusion: We observed substantial variability in both academic and social media dissemination of practice-changing SCD, Hem and thal gene therapy studies, though not statistically significant likely due to the limited number of studies overall. Higher citation count and Altmetric score in SCD studies may reflect recent robust dissemination efforts by ASH and patient advocacy groups. Intentional promotion across academic and media platforms increases awareness, helping with early dissemination of updated information that could have significant impact on patient outcomes.

Abstract Immune thrombocytopenia (ITP) carries an increased risk of thrombosis, which may be further amplified by splenectomy and thrombopoietin receptor agonists (TPO-RAs). Although each intervention has been individually studied for its thrombotic risk, data are lacking on the safety of postsplenectomy TPO-RA use. We conducted a retrospective cohort study of adult patients with ITP who underwent splenectomy between 2011 and 2024. Patients were stratified on the basis of postsplenectomy TPO-RA use. The primary outcome was incidence of thrombosis. Secondary outcomes included bleeding, mortality, and hematologic response. Time-to-event analyses and multivariate Cox regression were performed. Among 88 patients, 37 (42%) patients received TPO-RAs after splenectomy. Thrombosis occurred in 17 patients in the TPO-RA group vs 14 patients in the non–TPO-RA group (P = .07). The 10-year cumulative incidence of thrombosis was numerically higher in the TPO-RA group (57% vs 36%), with clustering of events within the 3 months of postsplenectomy TPO-RA initiation. Venous events predominated; arterial events were rare. No significant differences were observed in bleeding or mortality rates between groups. Platelet counts alone did not independently affect bleeding or thrombosis. TPO-RA use after splenectomy was not significantly associated with increased thrombosis risk. However, early initiation may coincide with a high-risk period, and the sustained numerical difference in cumulative incidence throughout follow-up highlights potential clinical relevance. These findings support the need for individualized thromboprophylaxis and prospective evaluation of TPO-RA safety in this setting.

Introduction: Romiplostim is a thrombopoietin receptor agonist approved by the US FDA for chronic immune thrombocytopenia (ITP) in patients who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. The recommended dose is 1 mcg/kg/week subcutaneously, escalated weekly by increments of 1 mcg/kg to achieve and maintain a platelet count of 50 x 10 9 /L g ( Kuter et al 2021). It has been postulated that starting at the maximum recommended dose of 10 mcg/kg/week in patients with severe bleeding may swiftly increase platelets and minimize bleeding ( Roumier et al 2021). However, this approach may also increase the risk of major thrombotic events (TE). It is unclear if the more aggressive dosing strategy results in more rapid, robust responses and a tolerable safety profile compared to the FDA approved approach. Methods: This retrospective chart review included adult patients who initiated romiplostim while admitted for ITP at a Mayo Clinic Enterprise site from May 2018 to May 2022. Outcomes included rate of TE at 30 days and 90 days and time to first TE in patients receiving initial romiplostim doses of < 5 mcg/kg (low dose, LD) and > 5 mcg/kg (high dose, HD), median time to platelet response (defined as platelets > 30 x10 9/L and > 50 x10 9/L on 2 separate checks) in LD vs HD, and cost to the institution comparing LD to HD. Outcomes were summarized using descriptive statistics. Statistical analysis was done using BlueSky. Fischer's exact test and chi-squared were performed for categorical data, and Wilcoxon rank sum test were done for continuous variables. Results: Forty-five patients met eligibility criteria: 33 (73%) received initial romiplostim doses < 5 mcg/kg and 12 (27%) received doses > 5 mcg/kg. The majority of patients (43/45 (96%)) presented with platelets < 50 x 10 9/L. The median age was 65 years (68 in LD vs 57 HD). There were 24 (73%) males in the LD group vs five (42%) in the HD group. At baseline, 64% (n = 21) of LD patients and 75% (n = 9) of HD patients presented with bleeding. Major bleeding (defined by 2019 ASH ITP guidelines) was present in 21% (n= 7) vs 17% (n = 2) of patients, LD versus HD, respectively ( Neunert et al 2019). The overall incidence of TE in this study was 24% (n = 11): LD 5 (15%) and HD 6 (50%) (p = 0.044) at 90 days. Median days to TE was 21 days, 12 days in LD group (range 5-21) vs 24.5 days (range 14-58) in HD group (p = 0.067). TE included deep vein thrombosis (DVT, n = 6), DVT with pulmonary embolism (n = 1), portal vein thrombus (n = 1), multiple brain infarcts (n = 1), splenic vein thrombus (n = 1), and left atrial appendage thrombus (n = 1). The median platelet count at the time of TE was 304 x 10 9/L, 415 x 10 9/L (range 58-900) in the LD group vs 323 x 10 8/L (range 33-1427) in the HD group (p = 0.79). Thirty-two (71%) out of 45 patients had a response to romiplostim: 22 in the LD group (71%) vs 10 (83.3%) in the HD group (p = 0.698). Of the patients that responded, the median time to response was 6 days in the LD group vs 11.5 days in the HD group (p = 0.09) The median dose at time of initial response was 2 mcg/kg in the LD group and 6 mcg/kg in the HD group. Wholesale Acquisition Cost (WAC) was used to determine the cost per dose, rounded to the nearest vial size. The average WAC for the initial dose in LD patients was $1806.80 compared to $6061.79 in HD patients. Conclusion:There was a significantly increased incidence of thrombosis in patients admitted with ITP that received initial romiplostim doses > 5 mcg/kg, with no differences in the time to platelet response. Careful consideration of risks versus benefits should be given prior to initiating romiplostim at doses higher than recommended doses.

Background: Warm autoimmune hemolytic anemia (WAIHA) is mostly IgG mediated (IgG+C3-), which may at times fix complement (IgG+C3+). Whether the clinical outcome of complement-fixing (C3+) WAIHA is different from that of non-complement fixing (C3-) WAIHA remains unclear. The goal of this retrospective study was to describe and compare the clinical characteristics and treatment outcomes of patients with C3+ and C3- WAIHA. Methods: We included adult WAIHA patients seen at our institution from 2001-2023 who met all of the following criteria: A) age >18 years; B) direct antiglobulin test [DAT] IgG+ + C3+ with no cold agglutinin; and C) biochemical evidence of hemolysis. Response to treatment was based on the international consensus criteria: complete (CR; normal Hb or Hb ≥12 g/dL, with resolution of hemolysis); partial (PR; Hb >10 but <12 g/dL or Hgb >12 g/dL without resolution of hemolysis); or no response (neither CR nor PR). 223 WAIHA patients were found, and 132 patients were ultimately included. The most common reason for exclusion was a lack of complete DAT that included C3 testing. Results: There were 59 patients with C3- WAIHA and 73 patients with C3+ WAIHA, reflecting 44.7% and 55.3% of total patients respectively. Pertinent demographic, clinical, and treatment information are shown in Table 1. Slightly over half (52.3%) were males and the mean age (SD) was 63.9 years (18.1). Concomitant lymphoproliferative disease was present in 34.1% of the patients. The 3 most common treatments were steroids (97%), rituximab (66.7%), and splenectomy (18.2%). The median follow-up from diagnosis was 20.0 months (range, 1.0-251.8 months), and 14.4% of patients had died at the time of this analysis with no difference between the groups (P=0.82). There was no significant difference in the demographic composition, clinical findings, and treatment received in both groups. The number of treatments received were similar between C3- and C3+ WAIHA groups (Table 1). After first line of treatment, response was achieved in 86.4% and 94.4% of the C3- and C3+ groups (P=0.12), respectively. Additionally, 62.7% of the C3- group and 80.8% of the C3+ group were in PR or CR by their most recent CBC (P=0.02). 33.9% and 43.8% of the C3- and C3+ groups relapsed at least once (P=0.25). In those who relapsed, there was an average of 2.6 relapse events in the C3- WAIHA group compared to 1.8 relapse events in the C3+ WAIHA group (P=0.03). However, there was no difference in time to first relapse between the groups (P=0.51), shown in Figure 1. Conclusion: There have been retrospective descriptions of multiple AIHA subtypes and response rates to different therapies; however, this is one of the first studies to our knowledge to focus specifically on outcomes between complement subgroups. In our large group of patients with C3- and C3+ WAIHA, the clinical presentation, treatments utilized, and response to treatment were similar. Our data suggest that C3- and C3+ WAIHA can be approached and treated similarly.

101 Background: In the US, minority patients are underrepresented in cancer clinical trials. This is due to multiple factors, including socioeconomic barriers, limited medical insurance coverage and restrictive clinical trial eligibility, e.g., ANC cutoff. For the latter, conservative ANC cutoff disadvantages Black patients. Two-in-three Black individuals have a Duffy-null phenotype, that is associated with lower ANC with 5% prevalence of ANC <1,500 cells/µl. To improve Black patient accrual to cancer clinical trials, lowering the ANC cutoff was proposed as a potential solution over a decade ago. Its implementation is not known. This study evaluates the ANC cutoff values as part of the eligibility criteria for cancer clinical trials. Methods: We accessed the Clinicaltrials.gov website on 5/25/2023 and obtained the ANC cutoff of cancer clinical trials conducted in the US. We included adult therapeutic trials in the phases of recruiting, not yet recruiting, enrolling by invitation, and active-not yet recruiting. Trials with drug interventions were selected. Those focusing on surgical, behavioral, nutritional and radiotherapeutic interventions were excluded. All ANC cutoff values were converted to “cells/µl” for analysis. Results: A total of 911 trials were evaluated, and 470 met the eligibility criteria. Of the 470 trials, 366 (78%) involved solid malignancies, and 104 (22%) involved hematologic malignancies. Hematologic trials have significantly lower ANC cutoffs compared to solid tumor trials with median ANC cutoff of 1,000 (range, 250-2000) vs. 1,500 (range 250-3,000); p=<0.001. In all, 323 trials (68.7%) required patients to have ANC >1,500, and 116 trials (24.6%), primarily hematologic, required patients to have ANC >1,000. For myeloma and prostate cancer, two cancers with higher incidence among Blacks, 12.9% and 86.4% of the trials require ANC >1,500, respectively. All genitourinary, breast, head & neck, sarcoma, lung, skin, and neuroendocrine tumor trials excluded patients with ANC <1,000. Conclusions: Most hematologic malignancy trials have a more liberal ANC cutoff allowing patients with ANC <1,500 to participate. However, solid tumor trials remain more conservative, with 4 in 5 trials requiring an ANC cutoff of >1,500. A strict ANC cutoff remains a barrier to minority accrual.[Table: see text]

TPS7080 Background: Myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPN) are classified as a distinct category under the World Health Organization (WHO) classification of myeloid neoplasms. MDS/MPN with RS and thrombocytosis (MDS/MPN-RS-T) and MDS/MPN, unclassifiable with > 15% bone marrow ring sideroblasts (MDS/MPN-U-RS) have similar clinical and pathological characteristics with symptomatic or transfusion-dependent anemia as the predominant morbidity. Luspatercept has been approved in myelodysplastic syndromes with ring sideroblasts (MDS-RS) and MDS/MPN overlap syndromes, based on the phase 3 MEDALIST clinical trial which primarily included MDS-RS patients with an objective erythroid response rate of approximately 40 per cent. In this trial, some MDS-RS patients also experienced an increase in neutrophil and platelet counts. This raises a safety concern for MDS/MPN patients with elevated platelet or WBC counts such as MDS/MPN-RS-T and MDS/MPN-U-RS. Previous studies have shown clinical and biological differences between MDS-RS and MDS/MPN-RS-T, with the latter group at a significantly elevated risk for thrombotic events. Additionally, several MDS/MPN-RS-T patients are on hydroxyurea which may blunt the erythroid response of luspatercept. Therefore, it is imperative to establish the safety and efficacy of luspatercept in this patient group. Methods: This is an investigator-initiated, prospective, phase II study of luspatercept in MDS/MPN overlap neoplasms with ring sideroblasts and thrombocytosis or unclassifiable with ring sideroblasts with 2 arms; hydroxyurea-independent (cohort A) and hydroxyurea-dependent (cohort B). Hydroxyurea and/or aspirin use is allowed as per investigator discretion. The primary goal is to study the efficacy and safety of luspatercept in MDS/MPN-RS-T or MDS/MPN-U-RS with symptomatic anemia. The primary endpoint is to assess erythroid response rate as per the 2015 International Working Group MDS/MPN response criteria. Secondary endpoints include response duration, time to acute myeloid leukemia (AML) transformation, thrombosis rate, AML-free and overall survival. Inclusion criteria include newly diagnosed or relapsed/refractory adult patients with WHO-defined diagnosis of MDS/MPN-RS-T or MDS/MPN-U-RS with symptomatic or transfusion-dependent anemia and unlikely to respond (EPO level > 200 IU/L) or intolerant to erythropoiesis stimulating agent (ESA) therapy. Prior therapy with lenalidomide, hypomethylating agents or immunosuppressive therapy is allowed. The overall plan is to enroll 54 patients across the three Mayo Clinic sites, Minnesota, Arizona and Florida. Enrollment to the trial began in January 2022 with 1 patient enrolled at the time of abstract submission. Clinical trial information: NCT05005182.

SummaryInstitutional database search (1999–2020) for acute myeloid leukaemia (AML) identified 109 cases of myeloid sarcoma (MS), of which 19 were isolated and presented de novo. The latter displayed longer survival (median 78 months), compared to MS with synchronous intramedullary AML (n = 32; median 16 months) and de novo AML without MS (n = 729; median 22 months; P = 0·13). However, the difference in survival was no longer apparent after accounting for bone marrow cytogenetic risk status (P = 0·67). Treatment‐induced MS tumour resolution was not affected by the presence of intramedullary disease (P = 0·61). The current study clarifies the prognosis of de novo isolated MS, in the context of AML.