bluuebunny/crossref_metadata_2025_split huggingface dataset:
Habit Efficacy Trial: A Multi-Site Randomized Controlled Trial of Community Health Worker Support to Increase Hydroxyurea Adherence of Youth with Sickle Cell Disease
Authors: Green Nancy S. , Manwani Deepa , Aygun Banu , Appiah-Kubi Abena , Smith-Whitley Kim , Jia Haomiao , Smaldone Arlene 
Published: December 2023

Introduction: Despite disease-modifying effects of hydroxyurea (HU) on sickle cell disease (SCD), poor adherence among affected youth commonly impedes treatment impact. The HABIT multi-site randomized controlled efficacy trial aimed to increase HU adherence.
Methods: Youth with SCD ages 10-18 years with impaired adherence were identified through laboratory evidence, primarily flagging levels of treatment-induced fetal hemoglobin (HbF). Eligible youth were enrolled as dyads with their primary caregivers for one year. We tested a 6-month phase of semi-structured supportive, multi-dimensional dyad intervention led by community health workers (CHW) with 4-5 visits addressing information, social issues/referrals, barriers, habit formation using goal-setting and cues, augmented by daily tailored automated text message reminders, compared to standard care. This phase was followed by a 6-month sustainability phase (months 7-12) of observation and, for the intervention group, 1 CHW booster visit. Primary intervention outcomes were 1) HbF levels compared to enrollment; and 2) proportion of days covered (PDC) for HU versus the pre-trial year. The secondary outcome was sustainability of these changes up to month 12.
Results: Starting in 2020, the COVID-19 pandemic disrupted enrollment and clinic-based procedures. The trial enrolled 50 dyads, missing target enrollment. Compared to enrollment levels, both HbF level and PDC significantly improved within the intervention group at month 6 (p=. 03 and . 01, respectfully), with parallel increased MCV (p=.05). Increased HbF did not reach signifance compared to controls (p=.07). No significant within- or between-group differences were found at month 12.
Conclusions: Within-group results suggest that our CHW-based dyad intervention with text message reminders improved HU adherence at 6 months but there were no between-group differences. Effects did not endure through the subsequent 6-month sustainability phase. These findings suggest that improved HU adherence for youth with SCD though our community-based, multi-modal support for youth-caregiver dyads temporarily improved usage. Durability of impact on adherence may require integrating CHW-led support and text reminders into clinical care.
Acute Cardiovascular Complications of Disseminated Intravascular Coagulation in Acute Myeloid Leukemia
Authors: Araji Ghada , Wei Chapman , Niazi Muhammad , Rajavel Anisha , Sharma Rubal , Grovu Radu , Siddiqui Fasih Sami , Mustafa Ahmad 
Published: December 2023

Background: Disseminated intravascular coagulation (DIC), an acute or chronic systemic process with multifactorial etiology, can present as a life-threatening emergency with the potential for causing thrombosis and hemorrhage. DIC may be seen with all leukemia subtypes, but it is an especially prominent feature of Acute Myeloid Leukemias (AML). DIC complicating AML can lead to a variety of complications and has been implicated in worse clinical outcome, however, its association with acute cardiovascular complications has not been reported before.
Methods: National Inpatient Sample (NIS) Database 2016 -2018 was used to procure individuals with AML, and baseline demographics and comorbidities were collected using ICD-10-DM codes. Patients with missing data or those receiving immunotherapy, chemotherapy, or radiation during hospitalization were excluded. Patients were stratified into those with and without DIC. Greedy propensity matching using R was performed to match the two cohorts in 1:1 ratio on age, gender, medications (aspirin/ antiplatelet/ anticoagulation) and fourteen other baseline cardiovascular comorbidities. Univariate analysis pre and post-match along with binary logistic regression analysis post-match were used to analyze outcomes. P-value of &lt;0.05 was considered statistically significant.
Results: Out of a total of 37344 patients with AML, 996 had DIC. DIC patients were younger, predominantly males, and had lower prevalence of baseline cardiovascular comorbidities. On pre-match univariate analysis, DIC patients had statistically significant higher mortality (30.2% vs 7.8%), acute myocardial infarction (5.1% vs 1.8%), acute pulmonary edema (2.3% vs 0.7%), cardiac arrest (6.4% vs 0.9%), and acute DVT/PE (6.6% vs 2.7%). Multivariate logistic regression model after matching showed similar outcomes with higher mortality (OR:4.63), acute myocardial infarction (OR:2.64), acute pulmonary edema (OR:2.75), cardiac arrest (OR:3.77), acute DVT/PE (OR:2.98), and acute heart failure becoming statistically significant (OR:1.89) in DIC patients.
Conclusion: DIC was significantly associated with higher mortality and acute cardiovascular complications in patients with AML. The underlying mechanisms involve a complex interplay of procoagulant factors, anticoagulant deficiencies, cytokine release, and endothelial dysfunction. Additionally, leukemic blasts and their interactions with platelets and endothelial cells contribute to microthrombi formation and subsequent organ damage. These findings highlight the importance of close cardiovascular monitoring and prompt recognition of complications in AML patients with DIC. Further studies are needed to corroborate these findings and develop targeted interventions for prevention and management of these complications.
A Novel Approach: Nanopore Sequencing of Native Cell-Free DNA in Diffuse-Large B-Cell Lymphoma Patients
Authors: Erblich Thomas , Sauer Carolin , Muyas Francesc , Ficz Gabriella , Cortes-Ciriano Isidro , Gribben John G. 
Published: December 2023

Introduction: Nanopore sequencing (NS), a third generation long-read sequencing technology, is increasingly being used to study cancer genomes. NS has many advantages over next-generation sequencing, including the capability to simultaneously extract base sequence as well as base modifications in the same run without any further library modification. Notably, its portability and ability to provide real-time data make it a potentially powerful tool for clinical applications. This study explores the use of NS to directly sequence native cell free DNA (cfDNA) from patients with diffuse-large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin lymphoma.
Methods: For this exploratory study, 20 patients with either a new diagnosis or relapsed DLBCL were enrolled. We adapted NS methods for cfDNA and sequenced cfDNA before each chemotherapy cycle using both an Illumina platform (as a control) and the Nanopore platform. For differential methylation, we also sequenced plasma cfDNA from five healthy donors on the Nanopore.
Results: Our findings demonstrate that we can directly sequence cfDNA on the Nanopore platform, obtaining a whole genome coverage (average 1.2x) with deeper coverage in some regions and also observe ~60% global DNA methylation level in CG context. From this data we are now analyzing regions that are differentially methylated (DMRs) between normal and DLBCL, determining SNV/Indel profiles, and comparing copy number variants (CNVs). These results will be available and presented at the time of the meeting.
Conclusions: NS is capable of detecting cfDNA and measuring methylation levels, offering a promising and potentially clinically applicable new approach for the study of cfDNA.
Future directions: As we continue this research, our vision is to leverage the portability and real-time data capabilities of NS for clinical applications. By simultaneously combining multiple genomic features with machine learning, we aim to develop a method for measuring lymphoma cfDNA-based MRD in DLBCL patients to be used in clinical settings.
Determining Clinical Practice Gaps for HCPs in Treating CLL Using CME-Based Surveys
Authors: Topping Ryan P. , Quill Timothy A. , Lamanna Nicole , Sharman Jeff P. 
Published: December 2023

Background: Targeted therapies have revolutionized the care of patients with chronic lymphocytic leukemia (CLL). In this context, new evidence continues to accumulate with the goal of optimizing the clinical use of these treatments as additional novel therapeutics continue to emerge. In this study, we sought to analyze current clinical practices of healthcare professionals (HCPs) regarding the care of patients with CLL, along with their awareness of the latest evidence on novel investigational therapies for these patients.
Methods: Between March 2022 and June 2023, we conducted multiple live and online continuing medical education activities designed for experts to provide HCPs with evidence-based recommendations for the treatment of CLL. Baseline polling questions and surveys designed to assess key aspects of HCP knowledge, practice patterns, and confidence in this area were assessed across the activities.
Results: Among 124 HCPs participating in educational activities between September 2022 and June 2023, 40% reported high confidence in their ability to plan optimal treatment strategies using BTK inhibitors for patients with CLL based on available evidence and guideline and expert recommendations. There was considerable discordance between HCP and expert treatment choices for various case scenarios in multiple educational activities; for example, for patient cases without del(17p)/ TP53-mutated/ IGHV-mutated CLL andbulky disease with diminished creatinine clearance, experts would recommend acalabrutinib with or without obinutuzumab for 77% of scenarios, while HCPs selected this treatment 35% of the time (Table).
Among 57 HCPs who participated in educational programs from March 2022 to February 2023, 26% reported high confidence in their ability to recognize and manage AEs with BTK inhibitors in patients with CLL. Challenging AEs associated with the currently available BTK inhibitors also were self-identified by HCPs (Figure). One half of responding HCPs (52%) were able to identify characteristics that would qualify a patient for inpatient administration of the initial doses of venetoclax because of increased risk of tumor lysis syndrome (n = 48).
Finally, among 213 HCPs participating in educational activities from September 2022 to June 2023, 43% were aware of recent data regarding the use of pirtobrutinib, an investigational noncovalent BTK inhibitor, for treating patients with CLL.
Conclusion: Our data suggest that many HCPs are challenged to optimally incorporate contemporary treatment recommendations into the care of patients with CLL and struggle to maintain knowledge of investigational therapies that may affect the treatment landscape in the near future. Continuing educational activities designed to improve the knowledge, competence, and confidence of HCPs in the care of CLL would benefit patients with this disease. A more detailed data analysis of treatment trends and knowledge by geographic location and role on the care team will be presented.
Clinical Characteristics of Light Chain Amyloidosis in an Underserved Patient Population
Authors: Samuel Nina , Shah Nishi 
Published: December 2023

Background
Primary or light chain (AL) amyloidosis is the most common form of systemic amyloidosis in which insoluble fibrils are deposited in various tissues and can ultimately lead to multi-organ failure. It is commonly linked to plasma cell dyscrasias which lead to the overproduction and deposition of immunoglobin proteins. Due to multi-organ involvement and difficulty in diagnosing patients with light chain amyloidosis, these patients are faced with greater challenges present with extensive disease especially in an underserved patient population in the Bronx. Our aim was to report clinical characteristics of patients at a tertiary care center in the Bronx
Methods
A retrospective analysis of 29 patients with AL amyloidosis were evaluated at Montefiore Medical Center from 2008 until 2023 was performed to determine demographics, clinical characteristics, and outcome measures. Patient demographics such as age, sex, and race/ethnicity as well as organ involvement, mode of diagnosis, and disease staging were determined. The Mayo 2004 staging system was used for staging at the time of diagnosis.
Results
29 patients with AL amyloidosis were identified at Montefiore Medical center from 2008-2023, the median age of diagnosis was 63 (range 36-87). There were 18 men (62%) and 11 women (38%). Most of the female and male patients were black with 5 (45%) and 9 (50%) respectively. One third of the population were Hispanic. Out of all the patients, 11 (38%) had positive bone marrow biopsies at time of diagnosis and the most common organ involvement was cardiac with 21 patients at 72% of the data set. 11 had renal involvement (38%) and 9 (31%) had involvement of the gastrointestinal tract. 11 of the patients were stage 3 disease (38%) and 9 patients had stage 1 and 2 disease (31%) each. Majority of patients had lambda light chain involvement (55%). 2 patients had concurrent TTR amyloidosis. In terms of follow-up, 4 patients have died while 4 patients have been lost to follow-up.
Conclusion
Our study reports the extensive organ involvement in our patient population. A third of the patients present with Stage III AL amyloidosis with most patients having cardiac involvement. We aim to report specific outcomes for this patient population at the meeting.
Trials in Progress: A Phase I/II Clinical Trial of Off the Shelf Universal Donor Natural Killer Cells Combined with Chemotherapy for Treatment of Relapsed/Refractory Acute Myeloid Leukemia (KARMA)
Authors: Lamb Margaret , Guinipero Terri L. , Lee Dean Anthony 
Published: December 2023

Background and Significance: Natural killer (NK) cells are cytotoxic lymphocytes that play a key role in recognizing malignant cells. In AML, qualitative and quantitative dysfunction of innate NK cells portends a poor prognosis and adoptive NK cell therapy has been shown to be safe and effective with minimal risk for GVHD (Ciurea et al. 2022; Silla et al. 2021). To circumvent cost and logistics restraints of per patient manufacture of NK cells, we developed a universal donor (UD) NK cell bank for “off-the-shelf” NK cells (UD FC21-NK cells). Donors with optimal NK cell characteristics are identified through the National Marrow Donor Program, and peripheral blood NK cells are expanded for two weeks by co-culture with irradiated K562 feeder cells expressing 4-1BB ligand and membrane bound IL-21 as previously described (Denman et al. 2012). We seek to study the safety and efficacy of multiple doses of UD FC21-NK cells combined with fludarabine and cytarabine (FLA) chemotherapy in patients with relapsed or refractory AML.
Study Design and Methods: This open label, single-center phase I/II study will include a dose escalation phase to establish safety and determine the recommended phase II dose followed by an expansion phase to estimate efficacy (complete response rate and MRD negative response rate). Up to 20 patients ages 18-25 with relapsed or refractory AML, including isolated extramedullary disease, will be enrolled. Exclusion criteria include active GVHD, uncontrolled infections, hematopoietic stem cell transplant within 3 months of enrollment, and donor lymphocyte infusion within 30 days of enrollment. Patients will undergo FLA chemotherapy followed by six doses of UD FC21-NK cells given thrice weekly for two weeks (Figure 1). Dose levels include 1 x 10 7 UD FC21-NK cells/kg/dose, 3 x 10 7 UD FC21-NK cells/kg/dose, and 1 x 10 8 UD FC21-NK cells/kg/dose. Patients may receive up to 2 cycles if they do not achieve a CR after cycle 1 or if necessary to bridge to transplant. Peripheral blood samples will be drawn weekly for immune correlatives including in vivo NK cell expansion and persistence. The trial is currently open to enrollment to adult patients with the intent to expand to pediatrics after demonstrating preliminary safety. Clinical trial information: NCT05503134
Examining Racial Disparities in Multiple Myeloma Research and Treatment
Authors: Petit Ryan , Cusnir Mike 
Published: December 2023

Multiple myeloma (MM) is a disease which occurs in all races, geographic locations, and ethnicities, however the burden of this cancer is especially prominent in the African American/Black population with prevalence estimated to be as high as two to three times that of the White population. As a result MM is the most common hematological malignancy in Black patients. Despite a higher disease burden, this population suffers disproportionate rates of mortality. From 2017-2022 Black men had a 6% higher incidence rate than White men, but a 19% higher mortality rate. This disparity in outcomes between ethnic groups is likely multifactorial. Some explanations include novel therapy underutilization, or prevalence of comorbid conditions. It may also be attributable to biological differences, such as an increase rate of immunoglobin A disease, and an increased rate of chromosome 14 translocations. There may as a result be a heterogenous response to novel MM therapy. Unfortunately, clinical trial participation of Black patients has been significantly underrepresented. Studies that sought to analyze the results of novel therapy trials in this population found a trend towards decreased efficacy, however, were unable to reach significance due to insufficient study participation.
We conducted a pooled analysis of interventional phase III clinical trials obtained from ClinicalTrials.gov data from 01/01/2000 to 12/31/2022. Studies who did not include racial/ethnicity data were excluded. There were 34 trials included in total that met this criteria and included in this analysis. There were 16,405 total enrolled patients analyzed. 13,618 (83.01%) were White, 1,255 (9.21%) were Asian, 777 (4.74%) were Black/African American, and 454 (2.7%) identified as Hispanic, with the remaining identified as other. Study participation was analyzed over time. Percentage of patients enrolled by year showed a negative correlation in Black/African Americans over the analyzed period.
Our analysis suggests greater efforts need to be made to ensure the enrollment of a more diverse and representative MM population. Although this disease is roughly twice as prevalent in Black populations, clinical trial study participation since 2003 involved 18-times more White than Black patients. Despite ongoing recognition of this problem, study participation in MM has continued to remain largely homogenous. Interventions that may improve this problem include fostering and rebuilding trust in the clinical trial system that was damaged from historical abuses, expanding clinical sites to more diverse areas, expanding/revising eligibility criteria, and employing changes to enrollment techniques that better represent the demographics of the population intended to treat. Ultimately, the clinical trials for an intervention should appropriately reflect the population who will use it, otherwise these novel treatments may have unexpected heterogeneity in efficacy and safety once employed clinically.
Demographic Disparities in Clinical Trial Enrollment of US Patients with Newly-Diagnosed Multiple Myeloma
Authors: Costa Bruno Almeida , Debnath Neha , Costa Thomaz Alexandre , Bertasi Raphael , Mouhieddine Tarek H. , Nath Karthik , Rossi Adriana C 
Published: December 2023

Background: Racial, ethnic and gender disparities impact the real-world reproducibility of clinical trials leading to drug approvals for hematologic malignancies. Interestingly, a prior abstract (Boisclair et al., 2022) has shown an equitable enrollment between US demographic groups in frontline trials for newly-diagnosed non-Hodgkin lymphoma. Although disparities in multiple myeloma (MM) trial participation have been oftentimes demonstrated, prior studies (Kanapuru et al., 2022; Alqazaqi et al., 2022) predominantly involved patients with relapsed/refractory MM (RRMM). To further assess this gap, we conducted a cross-sectional analysis of US demographic representation in phase II or III trials for newly-diagnosed MM (NDMM).
Methods: Clinicaltrials.gov was searched for completed NDMM trials with a recruitment period between 01/01/2007-12/31/2020. Studies limited to phase I data (n=10), enrolling &lt;30 patients (n=35), including RRMM or other malignancies (n=18), and/or recruiting outside the US (n=93) were excluded. We subdivided patients according to gender, race, and ethnicity. For each subgroup, total new cases of MM from 2007-2020 were identified via the Surveillance, Epidemiology and End Results (SEER) Cancer Statistics Explorer Network, with subsequent calculation of a trial enrollment fraction (TEF; number of trial enrollees divided by incident US cases). Pearson's chi-square test was used to compare TEF between subgroups, yielding odds ratio (OR) and 95% confidence interval (95%CI) values, with P&lt;0.05 deemed significant.
Results: Among the 194 trials found on initial review, 25 met the established criteria for inclusion (Figure 1). All studies (n=3,559) described the participants' gender, while only 18 (72%; n=3,129) reported race and 9 (36%; n=2,319) reported ethnicity. Overall, women showed a significantly lower TEF compared to men (OR, 0.88; 95%CI, 0.82-0.94; P&lt;0.001). When compared to White Americans, TEF was significantly lower for African Americans (OR, 0.71; 95%CI, 0.64-0.78; P&lt;0.001) and Asian Americans/Pacific Islanders (AAPIs; OR, 0.64; 95%CI, 0.22-0.41; P&lt;0.001). In studies reporting ethnicity, TEF was significantly lower for Hispanics compared to non-Hispanics (OR, 0.18; 95%CI, 0.14-0.24; P&lt;0.001).
Conclusion: Our cross-sectional analysis reveals an underrepresentation of women, African Americans, AAPIs, and Hispanics in NDMM trials conducted around the US. These findings are complementary to the enrollment disparities previously shown in RRMM trials. Through the implementation of a comprehensive diversity plan, MM trials must include a more inclusive representation of the US population affected by this blood cancer. Such an approach will not only enhance the external validity of these trials but also mitigate the impact of ascertainment bias and promote healthcare equity.