bluuebunny/crossref_metadata_2025_split huggingface dataset:
Racial and gender disparities in the incidence of thyroid cancer using Nationwide Inpatient Database.
Authors: Frasier Kelly , Javaid Saad , Li Vivian , Vinagolu-Baur Julia , Ortega Yaguachi Nataly , Rodriguez Evadne , Del Castillo Olivia , Batista Raquel , Jonas Kenlee , Palma Laura 
Published: June 2024

e18066 Background: This study aimed to conduct a comprehensive evaluation of the ethnic and gender disparities that exist in thyroid cancer. Despite the significant amount of research that has been conducted on the complex and multifaceted differences between races and genders in various forms of cancer, there is still a noticeable gap in the data available in patients with thyroid cancer. Therefore, this study comprehensively assessed these disparities and their potential impact on the risk of developing Thyroid cancer. Methods: Using the National Inpatient Sample 2020, we identified patients with Thyroid cancer as the primary diagnosis (local/regional and advanced metastatic). We analyzed baseline characteristics such as age, gender, insurance, and income status, and several comorbidities to assess the risk associated with Thyroid cancer. Log Binomial regression model was used to calculate the Risk ratios after adjusting for confounding variables. Results: A total of 6,471,165 patients were analyzed, and it was found that 7520 of them (0.1%) had Thyroid cancer. Among these patients, 44.8% were male, and 55.1% were female, p<0.001. Female patients demonstrated a higher risk of developing thyroid cancer as compared to males (RR= 1.41(1.27-1.57); p<0.001). Compared to white females, white males, black males and females exhibited a decreased risk of bladder cancer (RR=0.66(0.58-0.76),p<0.001; RR= 0.24(0.16-0.36),p<0.001 and RR= 0.53(0.40-0.68), p<0.001, respectively). Hispanic females (RR=2.67(2.26-3.16);p<0.001) and females of other races (RR=1.69(1.20-2.37); p=0.002) had increased risk of Thyroid cancer, while no difference in risk was noted in Asian males (RR= 0.38(0.09-1.56); p=0.18), females (RR= 0.94(0.39-2.28); p=0.90) and males of other races (RR=0.81(0.51-1.29); p=0.38). Compared to lower income group patients, patients with high incomes had an increased risk of thyroid cancer ($65,000-$85,999: RR=1.18(1.01-1.38), p=0.03 ; >$86,000: RR=1.30(1.10-1.52), p=0.001). The risk of thyroid cancer decreased with increasing age (36-45:RR=0.59(0.48-0.72),p<0.001; 46-64: RR= 0.25(0.21-0.29),p<0.001; >65: RR =0.24(0.19-0.30), p<0.001). Patients with Diabetes had decreased risk (RR= 0.31(0.27-0.36); p<0.001), while patients with Hypertension had increased risk of thyroid cancer (RR=1.30(1.16-1.47); p<0.001). Conclusions: The disparities in healthcare access and the unique challenges faced by high-risk groups have a profound impact on patients with thyroid cancer. A more comprehensive understanding of these disparities is essential to effectively support this vulnerable patient population and to identify preventive measures that can reduce the incidence of bladder cancer among high-risk demographic segments.
Real-world analysis of HyperCVAD + TKI for untreated Ph+ ALL.
Authors: Rakiewicz Tara , Keiffer Gina , Palecki Julia , Bernstein Andrew , Wilde Lindsay , Kasner Margaret T. 
Published: June 2024

e18500 Background: Tyrosine kinase inhibitors (TKI) have revolutionized the treatment of acute lymphoblastic leukemia (ALL) with t(9;22) (Ph+). A single-center, single-arm, phase II study published in 2017 reported excellent outcomes in adult patients (pts) treated with ponatinib + HyperCVAD alternating with high-dose methotrexate and cytarabine (HyperCVAD). Complete remission (CR) rate was 100% with 78% of pts achieving complete molecular response (CMR). 2-year (yr) event free survival (EFS) was 81% and overall survival (OS) was 80% with 9/37 pts undergoing allogeneic stem cell transplantation (SCT). This treatment's success changed standard of care for patients with Ph+ ALL; however validation of these findings is needed. Methods: We performed a real-world, retrospective analysis of adult patients with previously untreated Ph+ ALL treated with at least 1 cycle of HyperCVAD + ponatinib or an alternate TKI, at our institution between 2016 and 2023. The primary endpoint was 2-yr EFS. Kaplan-Meier method was used to estimate all time-to-event endpoints and proportions were estimated along with 95% confidence intervals. Results: 19 patients with a median age of 46 yr were analyzed. 18 pts were newly diagnosed; 1 pt had relapsed Ph+ ALL. Median follow up was 29.4 months (m). Baseline characteristics are in the table. All evaluable patients achieved a response (18/18). 1 pt died from septic shock within 4 weeks of treatment start (5.3%). All evaluable pts achieved CMR, defined as undetectable BCR/ABL1 transcript (17/17; 1 missing). Median time to CMR was 3.83 m [1.67, 9.30]. Of the 9 pts who underwent SCT, 5 (55.6%) received ponatinib and 4 (44.4%) received an alternate TKI (p=0.350). SCT was planned in 5 pts, but performed for molecular relapse (MR) in 4 pts. No pts had clinical relapse, but incidence of MR was 40.1%. 2-yr cEFS (defined as clinical relapse or death) was 89.2% [63.1%, 97.2%]. Median cEFS was greater than 32.6 m [32.6, ∞], but when defined as death or any relapse, it decreased to 18.40 m [7.27, ∞]. 2-yr OS was 89.2% [63.1%, 97.2%]. Conclusions: While 2-yr OS and EFS are similar in our cohort to published data, a surprisingly large number of patients experienced molecular relapse, which was not reported in the original trial. While our sample size was small, there was no significant difference in CR or transplant status for patients treated with Hyper CVAD + ponatinib versus alternate TKI. [Table: see text]
RNA expression-based risk stratification of de novo acute myeloid leukemia.
Authors: Kim Donghyun , Yu Yeonhwa 
Published: June 2024

e18503 Background: Prognostication of acute myeloid leukemia (AML) at initial diagnosis relies on the identification of certain underlying genetic abnormalities as proposed by the European LeukemiaNet (ELN) risk classification. However, AML is highly heterogenous at the molecular level and standard guidelines are often not straightforwardly applicable. In this study, we explored gene expression-based risk stratification strategies and found that FLT3 and NPM1 transcript level profiles can predict overall survival in de novo AML. Methods: The Cancer Genome Atlas AML (TCGA-LAML) project’s normalized RNA-Seq transcriptome profile (n=158) published in 2013 was analyzed with MATLAB software. "High” or “low” level of each gene was determined by the median RPKM of the cohort used as cutoff. P-values were obtained from Cox proportional hazards regression model. Results: The low-FLT3 level group was associated with superior median OS (mOS) compared to high-FLT3 group (24 vs. 16 months; p = 0.02), whereas high-NPM1 level group was associated with superior mOS compared to low-NPM1 group (26 vs. 12 months; p = 0.03). The mOS for high-FLT3/low-NPM1 and low-FLT3/high-NPM1 groups were 9 months and 27 months, respectively (p = 0.001). In high-FLT3/low-NPM1 and low-FLT3/high-NPM1 groups, composition of Cancer and Leukemia Group B (CALGB) cytogenetic risk category [favorable, intermediate, adverse] was [9%, 73%, 18%] and [32%, 49%, 19%], respectively; composition of French-American-British (FAB) classification [M0, M1, M2, M3, M4, M5, M6, M7] was [15%, 27%, 3%, 6%, 24%, 24%, 0%, 0%] and [3%, 14%, 41%, 19%, 22%, 0%, 0%, 3%], respectively; composition of FLT3/NPM1c mutations [ wt/wt, mut/wt, wt/mut, mut/mut, NOS] was [45%, 18%, 18%, 18%, 0%] and [61%, 14%, 7%, 14%, 2%], respectively. Conclusions: We demonstrate a de novo AML risk categorization method solely based on FLT3 and NPM1 RNA-Seq transcript levels. The mOS of high-FLT3/low-NPM1 group resembled that of ELN "adverse" risk group, whereas the mOS of low-FLT3/high-NPM1 group resembled that of ELN "favorable" risk group. High-FLT3/low-NPM1 group was composed of fewer "favorable” but more “intermediate” CALGB risk categories compared to low-FLT3/high-NPM1 group. Notably, considerably more FAB M0, M1 and M5 but fewer M2 and M3 classes were enriched in high-FLT3/low-NPM1 group compared to low-FLT3/high-NPM1 group. We also note approximately half of the cases analyzed were FLT3 and NPM1 wild-types and speculate FLT3 and NPM1 transcript profiles may represent a global oncogenic state regardless of the underlying FLT3 or NPM1 mutations. This is also supported by the previously reported FLT3 mutation-like transcriptomic profiles observed in FLT3 wild-type AML cases1). Reference: 1) Mosquera Orgueira A, et al. Gene expression profiling identifies FLT3 mutation-like cases in wild-type FLT3 acute myeloid leukemia. PLoS One. 2021 Feb 16;16(2):e0247093
Co-mutation landscape and its prognostic impact on newly diagnosed adult patients with NPM1 mutated de novo acute myeloid leukemia.
Authors: Yao Yiyi , Zhuo Nanfang , Zhou Yile , Mao Liping , Yang Min , Lou Yinjun , Tong Hongyan , Jin Jie , Wang Huafeng 
Published: June 2024

e18505 Background: 25-35% of adult patients with acute myeloid leukemia (AML) carries NPM1 mutation, characterized by aberrant cytoplasmic dislocation of NPM1 protein, which is generally associated with a favorable outcome in the absence of FLT3-ITD mutation. Indeed, for NPM1-mutated AML patients with different co-mutation profiles, identification of specific co-mutation combinations other than FLT3-ITD mutation is necessary for accurate risk stratification and contributes to identify the optimal population who may benefit from allogeneic hematopoietic stem cell transplantation (allo-HSCT) during post-remission therapy. Methods: Eligible patients included newly diagnosed adult patients (≥18 years old) with NPM1 mutated de novo AML (M3 excluded) treated at the First Affiliated Hospital of Zhejiang University School of Medicine for at least one complete course of induction therapy from October 2018 to December 2022. All patients received next generation sequencing (NGS) detection for diagnosis before treatment. Response was evaluated within two courses of induction chemotherapy. Overall survival (OS), event-free survival (EFS), and disease-free survival (DFS) were collected for endpoint analysis. Results: 178 patients were analyzed. Median age was 59 years old (IQR, 51-68). The co-mutated genes with a detection rate of ≥ 10% included FLT3, DNMT3A, TET2, IDH2, IDH1, PTPN11, NRAS, and WT1. The median follow-up was 26.2 months. Our results showed that in NPM1 mutated AML, co-mutations of IDH1, IDH2, and PTPN11-PTP domain were associated with favorable prognosis, while co-mutations of FLT3-ITD and DNMT3A were associated with poor prognosis. Interestingly, the adverse outcome trends brought by FLT3-ITD and DNMT3A co-mutations could be reversed by IDH mutation and PTPN11 mutations, respectively (Table). Besides, for NPM1 mutated AML patients combined with FLT3-ITD/ DNMT3A mutations, allo-HSCT after remission could significantly improve outcome ( P < 0.05), while similar results were not found in FLT3-ITD/ DNMT3A wild type patients. Conclusions: This study demonstrated that NPM1-mutated AML with different co-mutation profiles led to heterogeneous outcomes. For NPM1-mutated AML patients with adverse prognosis-related co-mutation combinations, allo-HSCT after remission may be a recommended strategy to improve outcome. [Table: see text]
A propensity score–matched comparison of cytoreductive strategies in patients with acute myeloid leukemia presenting with hyperleukocytosis.
Authors: Avetian George , Ho Thuy , Lee Hyun , Bouligny Ian Michael , Maher Keri Renee 
Published: June 2024

e18509 Background: Hyperleukocytosis (white blood cell (WBC) count greater than 100x109), which may lead to the clinical entity of leukostasis, is a hematologic emergency present at diagnosis in 18% of patients with acute myeloid leukemia (AML). There is controversy regarding the appropriate cytoreductive strategy, which may include cytoreductive chemotherapy, hydroxyurea, and/or leukapheresis. The American society for apheresis (ASFA) released guidelines in 2023 making leukapheresis a Category III recommendation, however significant heterogeneity and methodologic flaws exist in the evidence used to make these recommendations. Methods: Retrospective analysis of 58 patients at Massey Comprehensive Cancer Center between 2017 and 2023 who received either hydroxyurea alone (n=35) or both hydroxyurea and leukapheresis (n=23) for hyperleukocytosis at time of presentation for AML diagnosis was performed. Baseline characteristics including age, sex, Charlson Comorbidity Index (CCI), European LeukemiaNet (ELN) risk stratification, and WBC count prior to cytoreduction were collected. Comparisons of complete remission rates (CR/CRi), 30- and 60-day mortality, median overall survival (OS), and rates of therapy-induced tumor lysis syndrome (TLS) and disseminated intravascular coagulation (DIC) were analyzed using Kaplan-Meier, Fisher’s exact, Mann-Whitney tests, respectively on a propensity score matched cohort to account for differing initial WBC counts between the treatment groups. Results: PSM was used to match presenting WBC counts between the two cohorts. Other baseline characteristics including median age (65y v. 60y), median CCI (5 v. 4), ELN adverse risk rate (31.53% v. 26.1%) did not differ after PSM. No significant difference was found between the hydroxyurea group compared to the hydroxyurea and leukapheresis group, respectively, when analyzing for rate of CR/CRi (36.5% v. 43.5%), 30-day mortality (10.5% v. 17.3%), 60-day mortality (10.5% v. 34.8%), median OS (7.77 mo. v. 8.07 mo.), or rates of DIC (10.5% vs. 8.7%) and therapy induced TLS (0% v. 0%). Conclusions: Patients who received hydroxyurea alone had similar outcomes when compared to the combined treatment group with respect to median OS, CR/CRi, and mortality rates. These results are notable given that leukapheresis is not available at many medical centers and is a resource-heavy procedure, and especially so in light of new ASFA guideline changes. However, these results reflect the laboratory entity of hyperleukocytosis rather than the clinical entity of leukostasis. Further work is ongoing to assess impact of cytoreductive strategies in leukostasis in AML, and among different cytogenetic and molecular subtypes. Decisions for leukapheresis or other cytoreductive strategies should be made on a case-by-case decision at an experienced center when possible.
Predictors of disseminated intravascular coagulation in patients with acute myeloid leukemia with severe sepsis and septic shock.
Authors: Adla Jala Saisree Reddy , Gadhiya Dhruvkumar , Ramphul Yogeshwaree , Mal Madho , Tummala Nayanika , Dhaliwal Kanwar Bir Singh , Sakthivel Hemamalini , Dandwani Mehndi , Ramphul Kamleshun , Chennapragada Suma Sri 
Published: June 2024

e18511 Background: Multiple pathophysiological pathways predispose Acute Myeloid Leukemia (AML) patients to Disseminated Intravascular Coagulation (DIC). As sepsis can also trigger DIC, we aim to evaluate the predictors of DIC among AML patients with severe sepsis and septic shock. Methods: We queried adults with a diagnosis of AML and severe sepsis with septic shock admitted between 2016 and 2020 in the United States via the National Inpatient Sample(NIS). Patients ages <18 years were excluded from our sample. Multivariate regression models were used to estimate the impact of multiple factors on events of DIC among these patients. Results: Our sample consisted of 19545 cases of severe sepsis with septic shock in AML adults that matched our selection criteria. It included 1705(8.7%) patients who also experienced DIC during hospitalization. Several factors, such as medium (aOR 2.174, p<0.01) and high frailty risk (aOR 1.788, p<0.01, vs. Low frailty risk), history of nutritional anemia (aOR 1.580, p<0.01), cirrhosis (aOR 2.316, p<0.01), chronic kidney disease (CKD) (aOR 1.319, p<0.01), systemic lupus erythematosus (SLE) (aOR 1.845, p=0.040), Females (vs. Males, aOR 1.169, p<0.01), and patients covered by Medicaid (vs. Medicare, aOR 1.325, p<0.01) showed higher odds of DIC. In addition, those ages ≥60 years were less likely to experience an event of DIC (aOR 0.699, p<0.01), as DIC patients were younger (mean age 58.85 years vs. 62.43 years, p<0.01). Patients with obesity (aOR 0.605, p<0.01), smoking (aOR 0.772, p<0.01), and cachexia (aOR 0.738, p=0.038) also showed fewer events of DIC. However, no racial differences were found between Blacks(aOR 0.928, p=0.404) or Hispanics (aOR 1.019, p=0.831)(vs. Whites). DIC patients who died were also older (mean age 59.99 years vs. 56.19 years, p<0.01). Finally, we were also able to confirm that events of DIC led to poorer prognosis with a higher rate of all-cause mortality (70.1% vs. 47.6%, aOR 2.169, p<0.01). Conclusions: Factors increasing the risk of DIC in patients with AML and severe sepsis with septic shock included anemia, cirrhosis, CKD, SLE, medium and high frailty risk, female sex, and Medicare insurance. While we noted lower odds of DIC among patients who are ≥60 years old, obese, cachectic, and smokers, further hospital-based studies to evaluate the severity of their illnesses along with other variables that could be analyzed via the NIS should be encouraged.
Venetoclax combined with hypomethylating agents for favorable risk acute myeloid leukemia: A single center experience.
Authors: Bajwa Shammas , Parkin Brian , Gayle Arlene A. , Patel Rushang D. , Mori Shahram , Pancari Philip , Socola Francisco Andres 
Published: June 2024

e18514 Background: Favorable risk acute myeloid leukemia (FR-AML) is typically treated with intensive induction chemotherapy followed by high dose consolidative cytarabine. However, a subgroup of FR-AML are not candidates for high intensity induction because of advanced age, comorbidities, or poor performance status. For these patients, hypomethylating agents (HMA) combined with venetoclax (HMA-Ven) is inferred as the standard of care based upon results of the VIALE-A trial; however, that trial enrolled only intermediate or poor risk AML. The efficacy of HMA-Ven in FR-AML is unclear. Here we present a single center experience of this regimen in FR-AML. Methods: In this retrospective single center case series, we collected data from all patients >18 years old with newly diagnosed FR-AML between January 2018 to December 2022 at AdventHealth Orlando who were treated with HMA-Ven. Patient with relapsed/refractory disease or a diagnosis of acute promyelocytic leukemia were excluded. FR-AML was defined using ELN 2022 guidelines based on the results of genomic testing of the initial bone marrow aspirate. The primary endpoints were the complete remission (CR) rate and 1-year overall survival (OS). Statistical analyses were performed using the R survminer package. Results: Newly diagnosed FR-AML who received HMA-Ven were identified (n=12). The median age was 67.5 years. 3 (25%) cases had inversion of chromosome 16 and 9 (75%) had NPM1 mutations without FLT3-ITD mutations. 11 (92%) patients received decitabine and venetoclax. Patients received a median of 2.5 cycles of HMA-Ven, and all 12 patients achieved CR after one cycle of treatment. 6 (50%) patients were consolidated with intermediate-dose cytarabine (IDAC), 3 (25%) continued HMA-Ven, 2 (17%) underwent allogeneic stem cell transplant, and 1 (8%) received enasidenib. The 1-year OS was 80% (CI 0.59-1), and the median OS was not reached. 1 patient died due to chemotherapy toxicity with IDAC, and 1 patient died due to heart complications. 2 patients relapsed, 1 after IDAC and 1 after intolerance to further treatment after 6 cycles of HMA-Ven. Conclusions: Our findings suggest that HMA-Ven is an effective treatment for newly diagnosed favorable risk AML. All patients achieved CR with one cycle of treatment with most surviving more than one year. Large multicenter studies are needed to further validate these promising results.
Patients with relapsed/refractory mIDH1 AML who proceeded to transplant after olutasidenib treatment.
Authors: De Botton Stéphane , Watts Justin M. , Jonas Brian Andrew , Chao Mwe Mwe , Cortes Jorge E. 
Published: June 2024

e18516 Background: Hematopoietic stem cell transplantation (HSCT) in post-remission AML is potentially curative and can improve survival for patients at high risk of relapse. However, achieving remission in patients with relapsed/refractory (R/R) AML is difficult, and therapies that enable previously ineligible patients to proceed to HSCT are highly desired. Olutasidenib (OLU) is FDA-approved for treatment of R/R mIDH1 AML. In the pivotal cohort of the registrational, Ph2, open-label, multicenter trial of olutasidenib, 35% of patients achieved complete remission (CR) or CR with partial hematologic recovery (CRh) with a 25.9 mos duration of response. Here we report the characteristics and outcomes of patients treated with olutasidenib who then underwent HSCT. Methods: In the Phase 2 trial, the pivotal cohort enrolled adults with R/R m IDH1 AML. OLU was administered at 150 mg BID in continuous 28-day cycles. The primary efficacy endpoint was the CR/CRh rate. Patients who achieved remission and met criteria for transplant could proceed to HSCT with discontinuation of OLU. Data cutoff: June 18, 2021. Results: 153 patients with m IDH1 R/R AML received OLU monotherapy, and 16 (11%) proceeded to HSCT. In these 16 patients, median age was 61 (40, 67), 50% were male, and median BMI was 24 (18, 38). Baseline bone marrow blast count was 24% (6% - 60%). At baseline, 15/16 (94%) had intermediate cytogenetic risk and 1 was unknown. Time since diagnosis was 8.2 mos (1.5, 116.8). 8 (50%) were refractory and 8 were relapsed (2 for >12 months). Median number of prior regimens was 2 (range 1-7). All 16 had prior induction, 2 (13%) had prior HMA, 3 (19%) had prior HSCT, and 94% (15/16) had prior intensive chemotherapy (IC), 50% (n=8) of whom were IC-refractory. Response rates to OLU in the 16 patients prior to proceeding to HSCT were 75% CR/CRh (69% CR), 19% patients CRi and 6% stable disease (see Table). All 16 patients were alive at 100 days. Median survival from start of OLU treatment has not been reached. Overall survival probability was 94% (95%CI: 63, 99) at 12 months and 61% (95% CI: 32, 80) at 24 months. The safety profile of this subpopulation was consistent with the rest of the cohort. No deaths due to an adverse event occurred. Conclusions: Olutasidenib was effective in achieving remission in patients with mIDH1 R/R AML, thus enabling patients R/R to or ineligible for intensive chemotherapy at study entry to proceed to potentially curative HSCT. Clinical trial information: NCT02719574 . [Table: see text]