bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analyzing the characteristics and prognostic outcomes for patients with myelodysplastic syndrome with Q-gene deletion.
Authors: Nnawuba Kingsley Chinonyerem , Lockwood Matthew Blake , Nzeako Tochukwu , Guyo Zeytun , Al Fazal Mohammad , Jensen Hanna 
Published: June 2024

e18526 Background: Myelodysplastic syndromes (MDS) are a group of hemopoietic disorders in which the bone marrow is deficient in producing healthy mature blood cells. MDS associated with a deletion in the long arm of chromosome 5Q is a rare occurrence, but considered a good prognosis in comparison to other subgroups of MDS. There has been limited focus directed towards this variant of the disease, especially concerning outcomes among different demographics. Methods: The National Cancer Institute’s Surveillance, Epidemiology, and End-Result (SEER) registry research database 17 (2000 -2020) was used to assess & compare the outcomes for this variant of MDS in adult & AYA pts. Univariate & multivariate analyses was performed and cox proportional hazards regression was used to assess prognostic outcomes. A two-sided pvalue ≤0.05 was considered significant. Results: Analysing (table) 2,323 pts identified, 98.92% (n= 2298) were adults ≥40yrs, and 1.08% (n= 25) were AYAs. AYAs comprised 32% Hispanic, 4% Non-Hispanic Asian or Pacific Islander (NHAPI), 16% Non-Hispanic Black (NHB), and 48% Non-Hispanic White (NHW). Compared to adults, AYAs had higher proportions of Hispanics and NHBs but fewer NHWs. AYAs showed longer average survival (57.7 vs 33 months) than older adults. Females generally had longer survival periods than males in both AYA (64.4 vs 49.1 months) & adult (37.2 vs 26.4 months) groups. Among adult racial groups, Non-Hispanic Black females had the poorest prognosis (29.6 months), while Hispanic males had the worst prognosis overall (21 months). Among AYAs, Hispanic females had the worst prognosis (4 months), followed by Hispanic males (24.2 months). Conclusions: Our study shows AYAs are less likely to die from MDS compared to adults ≥40. Hispanic females appear to have a worse outcome than males in both age groups & is independent of other analysed prognostic factors. More research is needed to examine other prognostic factors with the aim of improving survival outcomes. [Table: see text]
Patient reported outcomes among U.S. Veterans living with myeloproliferative neoplasms.
Authors: Mathur Natasha , Tiu Andrew Chua , Brazeau Ann , Giocondo Natalie , Gill Puneet , Liu Shanshan , Diao Guoqing , Subrahmanyam Ramesh , Kessler Craig M , Jain Maneesh Rajiv 
Published: June 2024

e18528 Background: Myeloproliferative Neoplasms (MPNs) profoundly affect patients' well-being, necessitating effective symptom relief. Patient-reported outcomes are pivotal for care improvement, aligning with Centers for Medicare and Medicaid Services priorities. This study aims to assess MPN symptom burden among U.S. Veterans, examining risk levels, thrombo-hemorrhagic complications, medication use, information access, care, and service-connected benefits. Methods: Conducted as a cross-sectional survey from December 1, 2023, - January 22, 2024, all Veterans in the MPN Advocacy Education & International database were recruited. Symptom burden was assessed using the validated MPN Symptom Assessment Form Total Symptom Score (MPN SAF TSS), with descriptive statistics and T-tests employed for analysis. Results: Of 61 respondents, 88% were male, 92% Caucasian, 88% served during the Vietnam war. The mean age was 73±7, with MPN diagnosis at 64±9 and a mean duration of 44±10 years from service-connected exposure. Key findings included 56% Polycythemia Vera, 26% Essential Thrombocythemia, 16% Primary Myelofibrosis, 70% JAK2, 10% CALR, 3% MPL, 14% unaware of their mutation status, and 34% unaware of MPN risk status. Seventeen (28%) underwent phlebotomy, 64% used Hydroxyurea, 29% Ruxolitinib, and 3% Interferon. Fatigue and itching were the predominant and severe symptoms (Table), with 43% reporting no symptom improvement. Mean MPN SAF TSS of all respondents was higher than prior study by Emanuel et.al. which adjusted for MPN subtype (36.4 vs. 21.6, p<0.0001). Twelve (20%) reported bleeding and 10% reported venous thrombosis after MPN diagnosis, while 13% reported arterial thrombosis before MPN diagnosis. Twenty-two (36%) are not seeing an MPN specialist and 61% are not seeing a hematologist at their local Veterans Affairs Medical Centers. Twenty-three (38%) did not seek a second opinion while 43% do not have a caregiver. Respondents turn to MPN organizations (75%), physician offices (74%), Google Search (49%), Webinars (41%), and Facebook (23%) for information. Five (8%) received service-connected disability benefits. Conclusions: Veterans with MPNs endure a substantial symptom burden, surpassing previous studies, signifying suboptimal management. Limited access to care persists, necessitating enhanced support. However, self-reporting bias and potential limitations in activity assessment must be acknowledged. Efforts to enhance MPN awareness, specialized care, and support mechanisms are imperative for comprehensive management. [Table: see text]
A call for improved anemia treatments in myelofibrosis: A single-center retrospective study.
Authors: Yan John , Kamel Josette Mary , Goel Swati , Verma Amit 
Published: June 2024

e18531 Background: Anemia in myelofibrosis (MF) is associated with poor prognosis and decreased quality of life. Effective treatments are limited, posing a significant challenge in clinical management. This study aims to provide insights into the treatment of anemia in MF patients from an underserved urban tertiary care center. Methods: We retrospectively reviewed 88 MF patients referred to our center in the Bronx, NY between 2000 and 2023. Demographic data, presence of anemia (hemoglobin ≦10 g/dl) at time of diagnosis or referral (TODR), transfusion dependence ( ≥ 2 units on ≥2 occasions within 8 weeks), anemia treatments, disease modifying treatment, and anemia response to treatments (as defined by the IWG-MRT and ELN consensus report) were assessed via non-parametric tests and univariate cox regression. Events were defined as death from any cause or development of anemia. Patients with missing data were excluded. Results: Among 88 patients analyzed, 77 (87.5%) experienced anemia during the study period. Overall survival (OS) for anemic patients was 7.7 years with 31 deaths, versus only 1 death in the non-anemic group. 51 (60%) of patients were anemic at TODR. For patients not anemic at TODR, median time to anemia (TTA) was 31 months. Patients with HMR (n=24) had faster median TTA than those without (22 vs. 49 months, p = 0.1). All triple-negative (TN) patients (n=8) were anemic at TODR and had statistically lower initial hemoglobin compared to patients with driver mutations (7.4 g/dl vs. 9.9 g/dl, p = 0.0023). Among anemic patients (n=77), age > 65 was associated with poorer OS (HR 2.293, CI 1.076 - 4.887, p=.0315), while transfusion dependency (HR 2.093, CI 0.4777 - 0.9422, p=0.0697) and Ruxolitinib use (HR 2.843, CI 0.9912 - 8.155, HR 0.052) approached significance. Secondary anemia treatments did not impact OS (HR 0.9346, CI 0.4537 - 1.925, p=.854) and are summarized in the table. Most patients received Ruxolitinib (68.8%) and hydroxyurea (35.06%), while fewer received Momelotinib (N = 4), Pacritinib (N = 6), or Fedratinib (N = 4). Conclusions: Our findings highlight the limited effectiveness of current treatments in reducing transfusion burden and anemia in MF, and that patients of higher genetic risk may be more susceptible to developing anemia. Transfusion dependency and treatment non-response are marginally associated with poorer outcomes, emphasizing the need for newer therapies. [Table: see text]
Safety and feasibility of outpatient CAR-T therapy: A single center analysis.
Authors: Soror Noha , Davis Olivia , Diaz Adolfo , Day Silas , Machiorlatti Michael , Pandey Manu , Ibrahimi Sami , Khawandanah Mohamad Osama , Holter Jennifer , Asch Adam Steven , Al-Juhaishi Taha 
Published: June 2024

e19005 Background: Chimeric Antigen Receptor modified R Cell Immunotherapy (CAR-T) cell products have revolutionized the landscape of treatment of relapsed and refractory (R/R) B-cell malignancies and multiple myeloma. Yet, these therapies emerged with their own challenges, Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are the most common and serious adverse events. The model of CAR-T cell therapy in the University of Oklahoma is unique as it is designated as an outpatient therapy. Little is known regarding risk factors for hospitalization after CAR-T therapy. Methods: This is a retrospective analysis of all consecutive adult patients who had CAR-T therapy from 9/1/2019 through 9/30/2023 at the University of Oklahoma Health Sciences Center (OUHSC). Inclusion criteria were adult patients with hematologic malignancies who received an FDA approved CAR-T therapy. Exclusion criteria included patients who were younger than 18 at the time of infusion, those who received cellular therapy for solid tumors and those who received investigational CAR-T cell products. Descriptive statistics were created for continuous and categorical variables. Chi-Square analysis and independent samples t-tests were used to measure association with hospital admission and treatment response. Logistic regression was used to explore associations for all covariates with each outcome. SAS 9.4 was used to perform all analysis. An alpha of 0.05 was used to determine significance. Results: A total of 118 patients received outpatient CAR-T/Cellular therapy at OUHSC during the study period with 78 patients meeting the inclusion criteria. The mean age at time of infusion was 58.6 (range=18-85) with most being male (n=46, 59.0%), White (n=63, 80.8%), and overweight/obese (n=50, 64.1%). The majority of patients received anti CD19 CAR-T (n=64, 82.1%) while 18.0% received anti BCMA products. CRS grade 0,1 occurred in 79.5% of patients (n=62) and 79.2% of patients were hospitalized within 30 days after CAR-T therapy (Median day of admission post CAR-T=5.5). Of patients who were hospitalized 26% had grades 2-4 CRS. Complete remission was achieved in 54.7% of patients. We compared the hospitalized and non-hospitalized patients across multiple characteristics, there was no association or predictors of hospitalization found. Albumin was the only predictor for CR. Conclusions: Our study provides data for safety and feasibility of outpatient CAR-T therapy despite potential risks for hospitalization. There are no clear predictors for hospitalizations after CAR-T therapy except for the development of CRS and ICAN. Higher baseline (pre-CAR-T) serum Albumin level was associated with higher odds of achieving CR.
Prevalence of adverse events following bispecific antibody therapy in non-Hodgkin lymphoma: A meta-analysis.
Authors: Liu Alex John , Fonseca Rodrigo , Langlais Blake , Almader-Douglas Diana , Hilal Talal 
Published: June 2024

e19008 Background: Bispecific antibodies (BsAb) have emerged as a new treatment modality for relapsed/refractory non-Hodgkin lymphomas (R/R NHL). They exert their effect by binding to CD3 on T-cells and CD19 or CD20 on lymphoma cells, activating the T-cell to exert cytotoxic effects against the tumor and normal B-cells. Treatment related adverse events (TRAE) include infections, cytokine release syndrome (CRS), neurotoxicity (ICANS). This meta-analysis was conducted to assess prevalence of TRAEs from prospective clinical trials that evaluated BsAb in R/R NHL. Methods: A systematic review was conducted through PubMed, Embase, Scopus, Web of Science, and Cochrane to identify BsAb clinical trials in NHL through October 2023. Eligible studies included phase I-III trials evaluating BsAb in any type of NHL, either as monotherapy or combination therapy irrespective of prior lines of treatment. Primary outcomes of interest include infection, neutropenia, CRS, and ICANS. All studies were weighted equally. Pooled prevalence estimates of TRAE were calculated using common and random effects models. Heterogeneity tests were performed using Cochran’s Q test. Subgroup analysis examined infection rates in monotherapy versus combination therapy cohorts. Results: After screening 1039 studies, 36 clinical trials with 2162 patients were included. The lymphoma subtypes were diffuse-large B cell lymphoma, follicular lymphoma, and mantle cell lymphoma. The BsAbs included mosunetuzumab (13 studies), epcoritamab (10 studies), blinatumomab (5 studies), glofitamab (5 studies), odronextamab (2 studies), and AFM11 (1 study). The median age of patients was 66 years, and patients had received a median of two prior lines of therapy. Median follow-up duration was 9.1 months. The prevalence of all-grade infections was 35% (95% CI: 0.33-0.38; I2 = 79%). For grade ≥3 infections, the prevalence was 16% (95% CI: 0.14-0.18, (I2 = 77%). There were higher rates of all-grade infections in the combination therapy cohort (41%, 95% CI: 0.36-0.47) compared with the monotherapy cohort (33%, 95% CI: 0.30-0.36). All-grade and grade ≥3 neutropenia occurred in 31% (95% CI: 0.29-0.34; I2 = 80%) and 22% (95% CI: 0.20-0.24, I2 = 61%) of patients. CRS was observed in 45% of patients (95% CI: 0.43-0.48, I2 = 85%). Grade ≥3 CRS occurred in only 2% of patients (95% CI: 0.02-0.03, I2 = 0%, p = 0.99). ICANS occurred in 12% (95% CI: 0.10-0.14, I2 = 90%) while grade ≥3 ICANS was rare, at 3% (95% CI: 0.02-0.03, I2 = 0%, p = 0.99). Conclusions: BsAb is associated with nontrivial rates of infections and neutropenia. The rates of high grade CRS and ICANS are low. The heterogeneity of the findings could be attributed by an underreporting of TRAE and small sample sizes from various studies. These results highlight the need for vigilant practices to diagnose and treat infections early and consideration for antibacterial prophylaxis in this immunocompromised population.
Bridging therapies used in trials testing CAR-T therapies.
Authors: Prasad Vinay , Kaestner Victoria , Haslam Alyson 
Published: June 2024

e19011 Background: Chimeric Antigen Receptor T-cell (CAR-T) therapy can induce durable remission in some patients but requires time for a patient’s own cells to be reengineered to produce CAR proteins that can bind to and destroy cancer cells. During this time, bridging therapy is often used in debulking to reduce treatment toxicities and to control the disease while waiting for the manufacturing of CAR-T cells. Because bridging therapy often involves systemic treatment, the bridging therapies can induce responses, in and of themselves, in clinical trials testing CAR-T therapies. As such, we sought to assess bridging therapies used in CAR-T trials. Methods: Using the FDA labels (labels.fda.gov) to identify the indications and the pivotal clinical trials that led to the approval of each CAR-T cell therapy, we looked at which bridging therapies were used, whether multiple therapies were combined, response rates, and the reported adverse events associated with bridging therapy. We took note of all relevant comments regarding bridging therapy in the main paper and supplemental results. Results: Of the 11 studies testing CAR-T therapies, 10 reported the bridging therapies that were used in the study. Notably, only three of 11 studies provided clear information about which combinations of bridging therapy treatments were used during the trials. Of those that reported the types of bridging therapies (n=10), the most commonly used bridging therapy was dexamethasone, which was used in every study (10/10). The next three most commonly used treatments include rituximab (6/10), gemcitabine (5/10), and etoposide (5/10). Of the trials, 2/11 clearly reported whether patients had a complete response (CR), partial response (PR), or very good partial response (VGPR) to bridging therapy. 5/11 vaguely reported responses, using terminology outside of CR, PR, VGPR. 4/11 trials did not report or mention any response information in regards to bridging therapy. Of all the trials, 1/11 clearly reported adverse events associated with bridging therapy in the supplement, while 10/11 of the trials listed adverse events associated with the treatment groups, without clarifying those associated with bridging. Conclusions: Although patients are often refractory to first-line therapies, which share considerable overlap with the bridging therapies used, these therapies may still induce responses. Despite this possibility, the reporting of bridging therapy combinations and their subsequent response rates and adverse event rates, is highly variable. Of 11 pivotal clinical trials that led to the approval of a CAR-T cell therapy, none clearly reported bridging therapy data that encompassed all three categories (combinations used, response rates, adverse events). What is more, these data were often omitted completely. These findings highlight the need for greater transparency in the reporting of bridging therapy in order to more reliably assess the efficacy of CAR-T therapies.
Evolving patterns of transplant strategies for mantle cell lymphoma in the era of BTK inhibitors and CAR-T therapy.
Authors: Maddukuri Ashok , Inoue Yoshitaka , Rakszawski Kevin , Claxton David , Ehmann Christopher , Zheng Hong , Minagawa Kentaro , Mineishi Shin , Naik Seema 
Published: June 2024

e19012 Background: Mantle cell lymphoma is an aggressive lymphoma with poor survival after chemotherapy alone. Both autologous (auto) and allogeneic (allo) transplants have improved outcomes over the years, but transplant strategies most beneficial for MCL are not clearly defined. Recently, BTK inhibitors and chimeric antigen therapies (CAR T) therapy approach has changed the landscape of Mantle cell Lymphoma. Methods: Patient Population:A total of 71 patients underwent transplant for diagnosis of MCL at Penn State Cancer Institute, between March 1993 and March 2023. Median follow up was 3.1 years (32 days-9883 days) after transplant. Patient Characteristics: A total of 71 patients (62 M: 9 F) underwent transplants, including autologous (n=30), allogeneic (n=32), and CAR T (n=9). Since 2020, 19 transplants were performed: CAR T (n=9) auto transplants (n=9) and allogeneic transplants (n=1). Relapsed and refractory MCL (n=4) patients received CAR T whereas patients achieving CR 1 (n=8) and PR1 (n=1) received auto transplants. Most patients were Caucasian (n= 68), with few Hispanic (1), African American (1), or Asian (1). Results: Median age at the time of transplant was 61 (37-70) years for autologous, 56 (33-67) years for allogenic and 63 (55 -75) years for CAR T respectively. Disease status at transplant was CR 52.1% (n=37), primary induction failure or relapsed/refractory 36.6% (n=26), PR 11.3% (n=8). High LDH was seen at the time of transplant in 16.9% (n=12) patients and normal in 83.1%(n=59) patients. Blastoid morphology was seen in only 13.8% (n=4) autologous, 37.9% (n=11) allogenic and 33.3% (n=3) CAR T patients. Outcomes: Overall survival (OS) at 1 year and 3 years was 93.3% and 85.9% for autologous (auto) transplants, 62.5% and 52.9% for Allogeneic (allo) transplants, 88.9% and 76.2% for CAR-T therapy respectively (P = 0.007). Progression free survival at 1 year and 3 years was 86.3% and 75.0% for auto transplants; 50.0% and 43.3% for allo Transplants; 66.7% and 66.7% for CART Therapy (P = 0.03). Primary cause of death was Treatment Related Mortality (TRM) (n= 9) (GVHD=4; Pulmonary=3; MOF=2) and disease progression (n=10); unknown (n=4); other (n=1). Primary cause of death for CAR T therapy was grade IV ICANS and disease progression. Conclusions: Recently CAR T therapies have changed the landscape of MCL treatment algorithm in both Blastoid and non-Blastoid histology MCL patients. But in the era of CAR T therapy and BTK inhibitors for MCL, achieving CR at the time of transplant predicts improved long-term outcomes. Randomized studies or larger retrospective CIBMTR data analysis may be important to answer best transplant strategy for MCL patients. [Table: see text]
Risk of hypertension in patients with CLL/SLL who participated in ALPINE: A post hoc analysis.
Authors: Ramirez Dulce , Chen Lipeng , Zhang Jun , Aldairy Wassim , White William B. 
Published: June 2024

e19016 Background: Bruton tyrosine kinase (BTK) inhibitors are an important therapeutic option for patients with CLL/SLL. The first-generation BTK inhibitor, ibrutinib (ibru), is associated with an increased risk of hypertension. Zanubrutinib (zanu) is a next-generation BTK inhibitor designed to maximize BTK occupancy and minimize toxicity with fewer off-target effects. This analysis evaluated the risk of developing hypertension based on initiation of antihypertensives (anti-HTN) in ALPINE (NCT03734016). Methods: Anti-HTN use in the zanu (n=324) and ibru (n=324) treatment arms was assessed. The definition of anti-HTN was based on Standardized Drug Grouping; concomitant anti-HTN were adjudicated by an independent hypertension specialist blinded to BTK inhibitor assignment. Time to initiating new anti-HTN and time to adding a new class of anti-HTN were assessed using the Kaplan-Meier method. Comparisons of time-to-onset endpoints were analyzed based on the log-rank test. Results: At baseline, patient characteristics were generally balanced between zanu and ibru arms (median age, 66.7 vs 67.1 y; male, 65.1% vs 71.4%; history of hypertension, 50.9% vs 50.0%; type 2 diabetes mellitus, 10.1% vs 8.9%). Among patients not on anti-HTN at baseline, 20.7% (n=35/169) of zanu- and 28.7% (n=51/178) of ibru-treated patients initiated anti-HTN during the study. Among all patients, fewer patients in the zanu arm initiated new anti-HTN (28.4% [n=92/324] vs 32.4% [n=105/324]) and the anti-HTN were initiated later (hazard ratio [HR], 0.77; P-value=.071). Additionally, statistically fewer patients in the zanu arm compared with the ibru arm started anti-HTN in a new class (24.1% [n=78/324] vs 29.3% [n=95/324]) and the anti-HTN were started later (HR, 0.72; P-value=.034). The event rates for initiation of new anti-HTN or a new class of anti-HTN were consistently lower in the zanu vs ibru arm at each timepoint (Table). Conclusions: In ALPINE, initiation of new anti-HTN or a new class of anti-HTN occurred less frequently in the zanu arm vs the ibru arm in patients with CLL/SLL. Adoption of anti-HTN occurred sooner with ibru than zanu. These findings should be considered when initiating BTK inhibitor therapy in patients with CLL/SLL who have an elevated cardiovascular risk. Clinical trial information: NCT03734016 . [Table: see text]