bluuebunny/crossref_metadata_2025_split huggingface dataset:
Financial impact of immunotherapy-related adverse events among inpatient admissions with solid malignancies.
Authors: Pichardo Rayli , Abu Omar Yazan , Wang Ding 
Published: June 2022

e18825 Background: Immune checkpoint inhibitors (ICPis) have shifted the landscape of cancer treatment from conventional cytotoxic regimens. The mechanism of action involves suppression of immunologic checkpoints that often results on a unique spectrum of side effects associated with immune-mediated inflammations. The Aim of this study is to evaluate the financial impact from immune-related adverse events (IrAEs) reflected in hospitalized patients undergoing anti-neoplastic immunotherapy using the data from a nation-wide database. Methods: We performed retrospective analysis with the National Inpatient Sample (NIS) using ICD10-CM and PCS codes to identify patients with solid tumors hospitalized for immunotherapy between October 2015 and 2018. Inpatient data from patients with or without having developed IrAEs during the hospitalizations were compared in this study. IRAEs included systemic symptoms, diarrhea/colitis, hepatic and endocrine adverse events. Baseline characteristics and inpatient complication variables were collected and analyzed between these two groups. Results: From 5,795 admissions of ICPi-treated cancer patients, 1,160 patients or 20 % of these hospitalizations presented with IrAEs, females represented (37.5%) with an age of 57 years though not statistically different from admissions without IrAE. On the other hand, length of stay was statistically longer (7 vs 5 days, p < 0.05) with higher admission expenses ($184,255 vs $ 133,305, p < 0.05) from IRAE-associated admissions. Higher IrAEs were observed among patients who were ICPi-treated for genitourinary (GU) cancers (22% vs 15%, p < 0.05). IRAE as an independent risk factor was associated with higher costs even when adjusted for other risk factors, significantly contributed to a higher admission expenses by a coefficient at $46,624 (SE +/- $13,943). Conclusions: Although ICPi-therapies have offered various clinical benefits among cancer patients. They have also contributed to both direct and indirect costs of cancer management. Our analysis showed a higher IrAE incidence associated with ICPi-treated GU cancer patients, patients who developed IRAEs had a longer hospital stay and higher in-hospital mortality, resulting in higher care expenses as one of the indirect financial burdens of ICPi therapies, no differences were observed between gender, race, or income.[Table: see text]
Communication about cost of cancer care: Attitudes and practices of oncologists.
Authors: Khalid Ahmed Bilal , Urrutia Samuel , Hanna Nasser H. 
Published: June 2022

e18826 Background: With the cost of cancer care rising, it is becoming ever so important for physicians to be mindful of financial toxicity to their patients. Patient-provider cost discussions are associated with lower out of pocket costs (Hong el al, Value in Health 2020), yet few patients report having this discussion with their physician. There are few reports on oncologist’s preparedness, current practice, and barriers in discussing costs with their patients. Methods: An online survey was administered to hematology/oncology faculty physicians and fellows at the IU Simon Comprehensive Cancer Center. The objectives were to assess attitudes on communication about cost of cancer care and awareness around financial toxicity of cancer therapy. The questions included physician perception on patient’s attitudes towards cost discussion in clinics, current state of cost discussion in their clinic and their preparedness on having this discussion in the future. Results: 27/48 (56%) fellows and faculty members completed the survey. All respondents believed cost communication is associated with improved patient outcomes and 82% believed cost communication is desired by most patients. 22/27 (81%) indicated cost of care were discussed in less than half of patient encounters. 22/27 (81%) believed clear communication about cost should be a part of the patient’s clinic visit. When asked to rate their preparedness level on a scale of 0-100 on discussing cost of cancer care in their clinics, the median preparedness level was 20. Median awareness level about patient’s insurance plan was 20 and median awareness level about patient out of pocket cost was 21. 26/27 (96%) believed knowing cost of therapy and out of pocket cost would change the way they practice. 20/27 (74%) reported that not knowing the cost of cancer care themselves was the greatest barrier behind not discussing costs. Conclusions: Despite believing cost of cancer care should be discussed in the clinic, most hematologists/oncologists surveyed did not do so. Physician education on cost of cancer care and patient out-of-pocket costs is greatly needed.
Changes in oncology pharmacy benefit drug spend and trend in the United States.
Authors: Junk Christopher , Warde Prem R. , Hoversten Shanna , Sapkota Ujwal , Cavers William , Avalos-Reyes Elisea , Johnson Kjel Andrew 
Published: June 2022

e18832 Background: The American Cancer Society projects the total cost of cancer care to increase to approximately $246 billion by 2030, an increase of roughly 34% from 2015. Estimating the nature and extent of health care spending on cancer care is vital to understanding the scope of cancer costs. Additionally, this information will help inform the development of policies and programs to optimize the value of cancer care. The purpose of this study is to evaluate changes in oncology-pharmacy benefit (PB) spend and highlight areas that may be targets for value improvement. Methods: We identified patients with cancer using medical claims data from January 1, 2019, to December 31, 2020 at a large national Medicaid, Medicare, and commercial insurer. We defined total oncology spend (TOS) as the sum of allowed costs paid for medical and pharmacy claims per year, including chemotherapy, supportive therapy, radiology, radiation, emergency room, inpatient admission and evaluation and management. We compared the total oncology spend, by type of service, for each year by cancer for patients receiving therapies paid under the PB. Results: This study included 72,923 patients in 2019 and 52,486 patients in 2020. During this time, the top 3 disease states with the highest percent of oncology spend attributed to PB were chronic myeloid leukemia (CML), multiple myeloma (MM) and chronic lymphocytic leukemia (CLL). Approximately 87% and 77% of total oncology spend were attributed to PB chemotherapy among CML and MM patients, respectively. CLL costs varied by type of insurance with 80%, 26% and 19% of the total oncology spend attributed to PB chemotherapy in Medicare, fully insured and self-insured patients, respectively. When examining year-over-year changes in PB spend from 2019 to 2020, we observed an increase in total oncology spend in gynecologic cancers regardless of the type of insurance. Additionally, we observed increases in rectal, gastric, head and neck cancers and hepatobiliary cancers primarily driven by Medicare patients. Conclusions: The economic burden of cancer is substantial and expected to significantly increase in the future. In this study, we observed differences in total oncology spend by cancer type and insurance, a proxy for age. Identifying trends in cancer spending allows the development of programs designed to better optimize value for certain tumor types.[Table: see text]
The risks of thrombotic and bleeding events in patients receiving PEGylated asparaginase for treatment of acute lymphoblastic leukemia.
Authors: Mautner Ben , Pierce Eric , Mort Joseph , DiBenedetto Samantha , Wells Leah , Ghamsari Farid , Morse Emily , Morris Amy , Keng Michael Kenneth , El Chaer Firas 
Published: June 2022

e19015 Background: The prognosis of adult patients with acute lymphoblastic leukemia (ALL) has improved with the adoption of pediatric-inspired chemotherapy regimens. PEGylated asparaginase (PEG-Asp) is essential to these regimens. Although PEG-Asp is associated with an increased risk of coagulopathy, venous thromboembolism, and depletion of antithrombin III (AT3), there is limited data evaluating the risk of thrombosis and bleeding and optimal antithrombotic interventions in these patients are unknown. Methods: We performed a single-center retrospective study of patients ≥ 18 years-old who received PEG-Asp for B- or T-ALL at the University of Virginia between 2015 and 2020. The primary outcomes were the incidence of thrombosis and bleeding events. All patients received prophylactic AT3 repletion for activity level <60% & cryoprecipitate for fibrinogen <100mg/dL. None received prophylactic anticoagulation. All received prednisone during induction at a median daily dose of 1 mg/kg. Results: We identified 57 patients who received PEG-Asp for ALL. Median age was 32 years (range 18-63). Five patients (8.8%) had a thrombotic event during induction versus five (16%) during post-induction. Four patients (7%) had a bleeding event during induction versus five (10%) during post-induction. The most common type of thrombosis was deep venous thrombosis, with the majority being catheter-associated. Pulmonary embolism and CNS thrombosis were less common. During induction, the median time to thrombotic event was 18 days after last PEG-Asp administration. 60% and 80% of patients received AT3 and cryoprecipitate, respectively. During post-induction, the median time to thrombotic event was 58 days after last PEG-Asp administration. 38% and 63% of the patients received AT3 and cryoprecipitate, respectively. There was one episode of major bleeding during induction and six during post-induction. Conclusions: Though the increase in thrombotic risk in adult patients receiving PEG-Asp is well-characterized, rates of reported thromboses vary widely. Studies examining bleeding risk associated with PEG-Asp regimens are even scarcer and with variable outcomes. There was a significant occurrence of both thrombotic and bleeding events associated with administration of PEG-Asp. More investigation into the relative thrombotic and bleeding risks associated with PEG-Asp is needed to determine optimal antithrombotic interventions in adult patients with ALL.[Table: see text]
Inpatient outcomes of blinatumomab use: A national inpatient sample analysis.
Authors: Bakalov Veli , Tang Amy , Helfand Alexander M , Kancharla Pragnan , White Richard , Khattab Ahmed , Alhousani Mohammad , Samhouri Yazan 
Published: June 2022

e19021 Background: Blinatumomab, a bispecific (CD3/CD19) T-cell engager, is indicated for the treatment of acute lymphoblastic leukemia (ALL). The initial portion of each cycle is administered in the inpatient setting for close monitoring for cytokine release syndrome and neurotoxicity. Real world data are lacking on the cost of hospitalization, length of stay (LOS), and mortality in inpatients treated with blinatumomab. The goal of this study was to analyze the clinical outcomes of inpatient blinatumomab administration utilizing a national database. Methods: The ICD-10 diagnosis and procedure codes were used to identify Blinatumomab admissions and related complications from the 2018 version of the Nationwide Inpatient Sample (NIS) database from the Healthcare Cost and Utilization Project (HCUP). Weighted analysis was used to calculate national estimates. Logistic regression analyses were used to examine predictors of hospital outcomes (in-hospital mortality, length of stay, and cost), with p < 0.05 considered statistically significant. Data were analyzed using SAS v9.4 (SAS Institute, Cary, NC). Results: A total of 228 patients received inpatient blinatumomab in this cohort. Median age was 46 years old (IQR 26.8, 63.0) and 59.2% were males, 50.4% were white, and 47.4% had private insurance. The majority of patients received care at an urban teaching (96.1%) or large hospital (76.3%). The most relevant inpatient complications during hospitalization included hypotension (7.5%), pneumonia (6.1%), sepsis (9.2%), seizure (2.2%), neutropenia (6.1%), thrombocytopenia (14.0), tumor lysis syndrome (3.9%), and acute kidney injury (9.6%). Median LOS was 9.0 days (IQR 3.0-16.2) and median hospitalization charge was $114,936 USD (IQR 51,984.2-240,557.5). On multivariate regression analysis, dialysis (OR 1.67, 95% CI 1.05-2.65), blood product transfusion (OR 1.5, 95% CI 1.14-1.97), sepsis (OR 2.63, 95% CI 1.86-3.73), neutropenia (OR 1.86, 95% CI 1.23-2.81), and pancreatitis (OR 1.46, 95% CI 1.11-1.91) were all associated with longer LOS. Dialysis (OR 1.83, 95% CI 1.29-2.6), transfusions (OR 1.52, 95% CI 1.01-2.28), sepsis (OR 1.87, 95% CI 1.20-2.91) and neutropenia (OR 1.84, 95% 1.04-3.24) significantly increased the cost of hospitalization. Conclusions: In this cross-sectional study of a large national cohort of patients receiving inpatient blinatumomab, multiple blinatumomab associated toxicities led to increased LOS and cost of hospitalization.
Association of genetic variants and survival in patients with acute myeloid leukemia in rural Appalachia.
Authors: Gates Christopher , Shultz Carl , Petros William Phillip , Wen Sijin , Primerano Don , Hazlehurst Lori , Denvir Jim , Sdrimas Konstantinos 
Published: June 2022

e19022 Background: Many previous population health studies examining adults with acute myeloid leukemia (AML) are derived from national databases within large urban centers. To address the concern of under-representation of rural Appalachian population in cancer genomic databases, we performed exploratory whole exome sequencing in patients with newly diagnosed AML. As the only stem cell transplantation center in the state, WVU is uniquely situated to capture most of these patients from the state and surrounding area. Due to its unique industry and environmental exposures, we hypothesized that WV may have both different rates of mutations and differing outcomes than the nation as a whole. Methods: We performed whole exome sequencing on 26 patients with newly diagnosed AML from paired bone marrow and buccal samples that were obtained from 2015 to 2017. Whole exome sequencing libraries were prepared using Agilent SureSelect Human Whole Exome technology. The libraries were sequenced on an Illumina HiSeq1500 sequencer using paired end runs. Correlations between genetic variants and clinical outcome variables were examined via retrospective chart review. Variables measured included association between biomarker data and progression-free survival (PFS) and overall survival (OS). Results: Median patient age was 68 years and women represented 10 of the patients (37%). Twenty-one patients had de novo AML (84%), 3 patients had preceding MDS (12%), and 1 patient had therapy-related AML (4%). As per ELN criteria, 8 patients were favorable (32%), 12 were intermediate (48%), and 5 were adverse risk (20%). Eight patients proceeded to transplant with the following donors: 4 MUD (50%), DUCB (37.5%), and 1 haploidentical (12.5%). The median PFS and OS were 16.5 months and 26.6 months, respectively. Tobacco use was the largest known exposure with 7 patients. We noted a similar mutational trend compared to national TCGA data, except for an increased tumor mutation burden and higher frequency of the following mutations as seen in Table. Neither MUC3A or MUC5AC were identified in the TCGA database. Of our five patients with BCOR mutations, two had a co-existing FLT3-ITD mutation, one of which also had a NPM1 mutation. Two patients had secondary AML, while the other 3 had de novo disease. The median OS was 63 days. While not statistically significant, BCOR mutation was trending toward a poor prognostic indicator.Conclusions: Despite our small patient cohort, the findings provide further assessment of predisposing detrimental mutations in AML in the Appalachian region and associated survival outcomes.[Table: see text]
MUC family influence on acute lymphoblastic leukemia in Native American populations from Brazilian Amazon.
Authors: Alcântara Angélica Leite de , Pastana Lucas Favacho , Gellen Laura Patrícia Albarello , Vieira Giovana Miranda , Dobbin Elizabeth Ayres Fragoso , Silva Thays Amâncio , Pereira Esdras Edgar Batista , Barra Williams Fernandes , Rodrigues Juliana Carla Gomes , Fernades Marianne Rodrigues , Assumpção Paulo Pimentel , Guerreiro João Farias , Santos Sidney Emanuel Batista dos , Santos Ney Pereira Carneiro dos 
Published: June 2022

e19025 Background: The MUC family includes several genes previously associated with carcinogenesis and it is associated with solid neoplasms such as those of the gastrointestinal tract. As far as we are aware, there are no studies relating MUC genes to acute lymphoblastic leukemia (ALL), and this type of cancer is more frequent in the Amerindian population, which has been understudied. Therefore, the present work aimed to investigate the MUC family exome in Amerindian individuals from Brazilian Amazon, in a sample containing healthy Native Americans (NAM) and indigenous with ALL, comparing the frequency of polymorphisms between these two groups. Methods: The population was formed by 64 Amerindians from the Brazilian Amazon from 12 different ethnic groups, 5 of whom were diagnosed with ALL. We analyzed 16 genes from the MUC family (MUC1, MUC2, MUC3A, MUC4, MUC5AC, MUC5B, MUC6, MUC7, MUC12, MUC13, MUC15, MUC16, MUC17, MUC19, MUC20, MUC21) and found a total of 1858 variants. Results: After the quality filter, only 743 variants remained. Among them, we compared the frequency of each polymorphism in the LLA vs NAM group, which led to 77 variants with a significant difference, and, among these, we excluded those with LOW impact, resulting in 63. The 63 polymorphisms were distributed in 9 genes, concentrated especially in MUC 19 (n = 30) and MUC 3A (n = 18). Finally, 11 new variants were found in the NAM population. Conclusions: This is the first work with a sample of native americans with cancer, a population which is susceptible to ALL, but remains understudied. The MUC family seems to have an influence on the development of ALL in the Amerindian population, and especially MUC19 and MUC3A are shown as possible hotspots. In addition, the 11 new variants found point to the need to have their clinical impact analyzed. Keywords: MUC family; ALL; Susceptibility; Native American Populations; Brazil.
Efficacy and safety of high-intensity versus reduced-intensity induction in Philadelphia chromosome-positive all ineligible for HSCT.
Authors: Tran Valerie , Bouligny Ian Michael , Zacholski Kyle , Venn Chad Michael , Alnimer Yanal Mufeed , Ho Thuy , Maher Keri Renee 
Published: June 2022

e19031 Background: Treatment options for Philadelphia chromosome-positive (Ph+) ALL are increasing. When combined with TKIs, it is unclear if high-intensity regimens lead to a survival benefit compared to reduced-intensity regimens in patients that are not candidates for allogenic hematopoietic stem cell transplant (HSCT). In this study, we sought to examine outcomes of high-intensity and reduced-intensity induction regimens and concurrent TKI administration with respect to toxicity, response, and survival in non-transplant candidates. Methods: We retrospectively analyzed 31 patients with Ph+ B-ALL treated at our institution during January 2015 to January 2021 that were not candidates for HSCT. Baseline patient demographics were obtained, including age, performance status at diagnosis, cytogenetic and molecular profiling through NGS, doses of induction, toxicity, response, MRD analysis, and survival. The event for calculating the overall survival (OS) was the date of death and patients were otherwise censored at the date of last contact. Results: We divided the cohort of 31 patients into two sub-cohorts: a high-intensity cohort of 22 patients treated with TKIs and hyperCVAD, CALGB 10403, or ECOG 1910 and a low-intensity cohort of 9 patients treated with TKI + steroids + vincristine, TKI + steroids, or TKI alone. There was expectedly a significant difference in age between the two groups (p = .002) with more advanced age in the reduced-intensity cohort, though no difference in sex (p≥.999), ECOG score at diagnosis (p = .886), or Charlson Comorbidity Index score (p = .180). Grade 3 or higher toxicity was approaching statistical significance with more toxicity in the higher-intensity group (p = .075). With fewer deaths during induction, achievement of CR or CRi was higher in the reduced-intensity cohort (100% versus 73.7%), though was not significantly different between the groups (p = .288) and the median OS was not reached in either cohort (p = .935) after a median follow-up time of 3.29 years. Conclusions: Acknowledging the limits of a small sample size and retrospective nature of the study, there was no observed difference in survival between high-intensity and reduced-intensity induction with TKIs for patients ineligible for HSCT. Reduced-intensity inductions were associated with a trend toward less severe toxicity. These findings are suggestive that reduced-intensity induction with TKIs in Ph+ ALL may represent a reasonable option for those ineligible for HSCT. Prospective randomized controlled trials in this population are warranted.
Clostridioides difficile infection in hospitalized patients with leukemia: A nationwide analysis of incidence and outcomes.
Authors: Mansour Mahmoud , Abu-Farsakh Yomna , Darweesh Mohammad , Mahfouz Ratib , Obeidat Adham E. , Ghous Ghulam , Daglilar Ebubekir 
Published: June 2022

e19042 Background: Clostridioides difficile infection (CDI) is the most common cause of nosocomial diarrhea. The incidence and severity of CDI have increased in adults. However, CDI has not been well studied in leukemia patients in the recent years. This study aims to evaluate incidence, mortality, and health care burden in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL). Methods: The United States Nationwide Inpatient Sample was used to extract hospitalization data of patients admitted between Jan 1st, 2016, to Dec 31st, 2019. Using International Classification of Diseases 10th revision codes, we identified adults with a discharge diagnosis of CDI and a concomitant leukemia diagnosis. The control group included non-leukemia patients with CDI. Primary outcome was in-hospital mortality. Secondary outcomes were length of stay (LOS) and hospital charges. Multivariate logistic regression was used to adjust for relevant variables. Results: An estimated 1,235,465 patients were admitted with CDI during the study period. CDI incidence per 100 discharges was higher among leukemia patients, particularly in AML and ALL patients (4.1 and 3.6, respectively) vs. 1 in general population. After adjusting for comorbidities and demographic variables, AML and ALL were independently associated with increased odds of mortality (adjusted odds ratio [AOR] 2.19 and 1.90 respectively: P <0.01). Additionally, both AML and CML had significant mean increase in length of stay (7.2 and 3.1 days respectively; P <0.01) and hospital charges (115,245$ and 87,198$ respectively; P <0.01) compared to non-leukemia patients. Conclusions: Among leukemia patients admitted with CDI, those with AML and ALL have significantly higher adjusted odds of mortality, length of stay, and hospital charges. AML and ALL patients also had the highest incidence of CDI. Applying antibiotic stewardship and appropriately diagnosing and treating CDI is pertinent in these high-risk patients.[Table: see text]