bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shattering myths regarding Hispanic ethnicity and survival in acute myeloid leukemia: Insights from the National Cancer Database.
Authors: Premnath Naveen , Khan Adeel , Pandey Mohak , Pandey Urvashi , Hoff Fieke W , Chung Stephen , Ramakrishnan Geethakumari Praveen , Collins Robert , Paulk Elizabeth , Sweetenham John W. , Madanat Yazan F 
Published: June 2023

7032 Background: Previous smaller studies suggest that despite younger age at presentation, Hispanic patients (HP) with acute myeloid leukemia (AML) have worse prognosis than non-Hispanics patients (NHP). Methods: We queried the National Cancer Database (NCDB) between 2004 to 2017 for adults aged ≥18 years for a diagnosis of AML using the ICD-O-3 diagnosis code. Baseline characteristics and outcomes were compared. Results: A total of 144,146 patients with AML were identified during the study period of which 9173 were Hispanic (6.4%). The median age at diagnosis was 66 years overall. Hispanics were younger at presentation with median age 55 compared to 67 in non-Hispanics ( p< 0.001). A higher proportion of HP were uninsured and in the lowest income quartile compared to NHP across all AML subtypes. HP had statistically significant longer survival across AML subtypes except for tAML. When adjusted for age, sex, Charlson Deyo Comorbidity Index, insurance, chemotherapy, transplant, and income status using a multivariate Cox regression analysis, HP had non-inferior survival to NHP. Conclusions: We present the largest study to date in Hispanics with AML. Hispanics presented at younger ages and had worse socioeconomic factors compared to NHP and when adjusted for multiple variables, did not have worse outcomes as reported in prior data. We believe previous studies in HP demonstrating worse prognosis may reflect bias and confounding given smaller patient numbers and are suggestive of disparities in access to health care and present opportunities for improvement. [Table: see text]
Clinical outcomes of patients with newly diagnosed acute myeloid leukemia receiving treatment in a safety-net hospital system.
Authors: Lu Jason , Bhakta Preeya , Lachowiez Curtis Andrew , Apostolidou Effie 
Published: June 2023

7035 Background: Standard induction therapy for acute myeloid leukemia (AML) results in 5-year overall survival (OS) rates of 30-45%. Further risk stratification and novel therapeutic options have improved 5-year OS rates to 75-80% in certain subgroups. Despite these advances, many patients lack proper socioeconomic resources, leading to limited access to new therapies, clinical trials, and hematopoietic cell transplantation (HCT), which remains the only curative therapy for AML. Many of these patients receive care within publicly funded ‘safety net’ institutions designed to serve all individuals, regardless of ability to pay, insurance status, or immigration status. Outcomes of historically underserved patients with AML treated within a large county hospital system remain unknown. Methods: This retrospective cohort analysis evaluated clinical outcomes of patients aged ≥18 years with newly diagnosed AML (ND-AML) treated in the Harris County Health System, Houston, TX, from January 2005 to July 2019. Results: One hundred ninety-two patients with ND-AML were included (de novo AML [n = 140], secondary AML [n = 45], and therapy-related AML [n = 7]). Median age was 52 years (range: 19-89) at diagnosis, and 102 (52.3%) were male. Most patients identified as Hispanic (n = 110). Sixty-two percent of patients were uninsured or indigent, receiving care under the county’s financial assistance programs. The majority had adverse risk 84 (44.3%), while 78 were intermediate (40.6%), and 26 favorable risk (13.5%). Standard induction therapy was administered in 172 (88%) of patients. Cytarabine and Anthracycline (7+3) based regimens were most commonly used (72.8%). 192 patients were evaluable for response. 139 (72.4%) achieved composite complete remission (CR/CRi) and 41 (21.4%) had primary refractory disease. For those who achieved CR after first or second induction, the median duration of CR was 16.7 months. with 25 (13.7%) ultimately receiving HCT. Common reasons for not receiving HCT included lack of insurance (19.2%) or non-citizen status (23.1%) (n = 77). 82 of the 139 patients who achieved CR relapsed. After a median follow up of 16 months, five-year OS rates were 20.7% from our entire cohort of patients. Conclusions: In this cohort of patients treated in a safety-net system, median OS and EFS were lower than reported outcomes in the past decade. In addition, only 13.7% received HCT, one of the only curative treatments for AML. Some barriers included inability to refer to transplant center due to lack of financial support or immigration status. Addressing socioeconomic and institutional barriers to AML therapy and HCT will advance care for disadvantaged patients, thereby improving outcomes of patients AML.
A step toward genomic equity: Mutational profiling of patients with myeloid neoplasm in the largest minority-serving hospital in metropolitan Chicago.
Authors: Elsebaie Maha AT , Turk Ekrem , Deenadayalan Vaishali , Obeidat Khaldun , Nanaa Ahmad , Zia Maryam , Birch Noah W. 
Published: June 2023

7037 Background: Information on genomic landscape of myeloid neoplasms comes from large studies of patients with predominantly European ancestry. Minority-serving hospitals offer unique opportunities to study ethnically diverse populations. Methods: In this retrospective study at the Stroger Hospital of Cook County, we included patients ≥18 years old with myeloid neoplasms or premalignant conditions who underwent mutational profiling via next generation sequencing (NGS). We utilized two commercially available myeloid panels: “ FoundationOneHeme” (406 gene panel) and “ Tempus” (648 gene panel) . Patient demographics were collected, including self-reported race/ethnicity. We compared data distribution using Kruskal-Wallis, Pearson’s χ2, or Fisher’s exact tests. Overall survival (OS) probabilities were compared using the log-rank test. Results: Ninety-four patients underwent NGS between 04/01/2020 and 12/31/2022, including 45 females (47.9%). 38 patients (40.4%) identified as Black, 28 (29.8%) as White, and 28 (29.8%) as Other (10.6% Asian, 9.6% Mexican/South American, and 9.6% undetermined). 30 patients (32%) identified as Hispanic and 64 (68%) as Non-Hispanic. Diagnoses included Acute myeloid leukemia (AML, 32%), Myelodysplastic syndromes (MDS, 13%), MDS/MPN overlap syndrome (7%), and Clonal Hematopoiesis of Indeterminate Potential (7%). Eighty-eight patients had at least one pathogenic variant and harbored 259 mutations in 74 genes. Commonly mutated genes were ASXL1 (23%), JAK2 (17%), DNMT3A (14%), and TET2 (13%).Non-White patients were more likely to have IDH2 mutations (5% Black vs. 0% White vs. vs. 14% Other races, p=0.011). Mutation count didn’t differ between racial p=0.525 or ethnic groups p=0.345. AML & MDS patients were more likely to have TET2, RUNX1, TP53, and IDH2 mutations. In addition, 24% of AML & MDS patients had mutated ASXL1. TET2, SRSF2, and RUNX1 mutations were common among MDS/MPN patients (Table). AML & MDS patients had poor OS, but OS didn’t differ between racial/ethnic groups. Conclusions: Premalignant mutations (e.g., ASXL1, TET2) predominated in our patients and tended to co-occur, increasing the overall mutational burden. Non-White patients were more likely to have IDH2 mutations. Adverse markers were common among AML & MDS patients, likely contributing to their dismal survival. Studies inclusive of ethnically diverse patients are needed to accurately translate genetic findings into clinical practice. This report from a large, minority-serving hospital represents a step toward promoting genomic and healthcare equity. [Table: see text]
Evaluation of cardiac failure and recovery in acute myelogenous leukemia.
Authors: Wu Matthew , Russell Katie , Shaw Carole , Halpern Anna B. , Ghiuzeli Cristina Maria , Appelbaum Jacob , Hendrie Paul , Walter Roland B. , Percival Mary-Elizabeth M. 
Published: June 2023

7038 Background: Cardiac failure causes significant comorbidity and death in acute myeloid leukemia (AML) patients, with incidence estimated at 10-15% (Neuendorff N Blood Adv. 2020). We sought to describe the post-treatment cardiac experience in AML survivors including factors associated with onset, persistence, and outcome of cardiac dysfunction during and following treatment. Methods: 86 patients with AML or other high-grade myeloid neoplasms treated with induction chemotherapy with or without allogeneic hematopoietic cell transplant were identified at the University of Washington/Fred Hutchinson Cancer Center from 1/2000-1/2022. All patients sustained cardiac dysfunction, defined as left ventricular ejection function (LVEF) decline of 10% with absolute LVEF below 50% during chemotherapy. A multivariable analysis was performed to compare those who recovered (LVEF recovery) and those who did not (LVEF non-recovery), examining baseline health factors, disease risk (ELN 2017), time to dysfunction and recovery, most probable cause of cardiac dysfunction based on cardiologist evaluation, and goal-directed medical therapy (GDMT) use and dosage. Results: 48% (41 out of 86) failed to recover following LVEF decline. This cohort tended to be older, male, and had more ASCVD risk factors ( p < 0.05). Neither the choice of chemotherapy regimen ( p= 0.43) nor the cumulative anthracycline dose ( p= 0.44) was significantly different between the LVEF recovery and non-recovery groups. Onset of cardiac dysfunction tended to occur later in the LVEF recovery cohort (median 72 vs. 48.5 days, p= 0.660). In subjects who recovered, the median time to recovery was 87 days (range 2-268 days). When chemotherapy was identified as the probable cause, it was associated with greater likelihood of eventual recovery ( p= 0.014), whereas ischemic coronary etiology was associated with non-recovery ( p= 0.005). Failing to recover from cardiac dysfunction correlated with shorter survival (median 229 vs 650 days, p = 0.005). Multivariable analysis is shown in the Table below. Importantly, the use of GDMT with higher doses of renin-angiotensin inhibitor medications (RAASi) were associated with higher probability of recovery (not shown, p < 0.05). Conclusions: The present study demonstrates recovery occurring in over half of AML patients who experienced cardiac dysfunction during their chemotherapy. Recovery was more common in patients whose cardiac dysfunction is precipitated by chemotherapy and in patients who received GDMT with aggressive use of RAASi. Since cardiac recovery was associated with improved survival, next steps include establishing a cardiac monitoring algorithm to initiate early and aggressive GDMT. [Table: see text]
Analysis of short-term efficacy and safety of mitoxantrone hydrochloride liposome regimen therapy in adult acute myeloid leukemia.
Authors: Ma Jun , Hu Junbin , Liu Li , Chen Yuqing , He Aili , Lou Shifeng , Ge Jian , Qi Kunming , Yang Yanli , Ye Jingjing , Cheng Hai , Lu Yinghao , Wang Linhui , Cai Huili , Wei Xudong , Yang Xiangdong , Xue Hua , Wang Hongxiang 
Published: June 2023

7039 Background: Acute myeloid leukemia (AML) is highly heterogeneous, and more than half of patients (pts) will experience refractory or relapse, with poor prognosis. Currently, chemotherapy and hematopoietic stem cell transplantation (HSCT) are the main treatments for AML. Mitoxantrone is a synthetic anthracenedione anti-cancer drug that is effective in lymphoma, leukemia, and other solid tumors. Mitoxantrone hydrochloride liposome (PLM60) is the first approved mitoxantrone nano-drug, which has shown favorable pharmacokinetic characteristics and significantly prolong the survival time of animals compared with the same dose of mitoxantrone (Li 2008). However, there is still a lack of systematic reports about the real-world application of PLM60 in AML. Methods: We performed a multicenter retrospective analysis of 82 pts with newly diagnosed AML and relapsed/refractory (R/R) AML, who received at least one cycle of PLM60 regimen between January 2022 and November 2022. Pts aged 18 years and above with confirmed diagnosis of AML according to the 2016-revised WHO criteria were eligible for inclusion, except acute promyelocytic leukemia (APL). The median dose of PLM60 in the regimen was 20.0 (range 10.3–31.6) mg/m2. Efficacy was assessed by composite complete remission (CRc) rate and overall response rate (ORR), and logistic regression analysis was performed to analyze factors affecting the curative effect. Adverse events were assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: 82 pts were enrolled with a median age of 50.5 (range 20-83) years. There were 71 cases of de novo AML and 11 cases of secondary AML. Targeted sequencing was performed on 86.6% of pts (71/82). FLT3 was the most commonly mutated gene found in 22.5% (16/71), followed by ASXL1 mutated in 12.7%, NPM1 in 11.3%, and TP53 in 11.3%. 4.9% (4/82) of pts underwent HSCT. Among the 25 newly diagnosed pts, CRc rate was 72.0% (18/25) and ORR was 92.0% (23/25). Among the 57 R/R pts, CRc rate was 24.6% (14/57) and ORR was 40.4% (23/57). The courses of induction failure ( OR= 16.617, P= 0.026), and the duration of the first complete remission (CR1) ( OR= 20.647, P= 0.007) were independent influencing factors of the efficacy. Common grade 3/4 AEs included decreased neutrophil count (84.1%), thrombocytopenia (76.8%), anemia (73.2%), febrile neutropenia (47.6%), pulmonary infection (11.0%) and upper respiratory tract infection (2.4%). The overall safety was acceptable and controllable. Conclusions: The PLM60 regimen had an encouraging efficacy and showed a manageable safety profile with the most adverse events being hematologic toxicities.
Comparison of characteristics and prognostic impact of FUS-ERG and AML1-MTG16 fusion genes in adult AML patients: A retrospective study from 1988 to 2022 with a medical database.
Authors: Zhou Ziyue , Zhou Yile , Yao Yiyi , Mao Liping , Zhang Yi , Hong Qing , Zhuo Nanfang , Pan Peifeng , Tong Hongyan , Jin Jie , Wang Huafeng 
Published: June 2023

7042 Background: AML1-MTG16 and FUS-ERG are two rare fusion genes in acute myeloid leukemia (AML). Their clinical characteristics and factors influencing prognosis have been summarized in a cohort of pediatric patients, but no systematic review is approached in adult. Methods: We retrospectively analyzed the clinical data of adult AML patients with AML1-MTG16 or FUS-ERG fusion genes, who were reported on Mitelman Database, PubMed and China national knowledge infrastructure (CNKI) from 1988 to 2022 or have received treatment in the First Affiliated Hospital, Zhejiang University School of Medical, and compared them with patients with RUNX1-RUNX1T1, exploring their clinical features and prognosis. Results: 314 patients were totally included for analysis. In comparison of RUNX1-RUNX1T1 group (n = 209), FUS-ERG-positive patients (n = 108) significantly exhibited a younger onset age (34.5y vs. 41y), higher WBC count (16.7 ×109/L vs. 10.4×109/L), higher recurrence rate (61.8% vs. 30.4%), and a worse response to chemotherapy (complete remission rate: 71.6% vs. 91.8%), while patients with AML1-MTG16 (n = 24) presented primarily as the secondary AML (83.3%) with a significantly elder age (56y vs. 41y). The FUS-ERG patients had a worse median overall survival (OS) of 13 months (95%CI: 11.6-14.4, P < 0.01) and a worse median disease free survival (DFS) of 7.5 months (95%CI: 6.5-8.5, P < 0.05) than control group, which also occurred in those had AML1-MTG16 gene with a median OS of 18.5 months (95%CI: 12.4-24.6, P < 0.01) and a median DFS of 14 months (95%CI: 3.7-24.3, P = 0.10). As shown in the table below, CR after induction chemotherapy, hematopoietic stem cell transplantation (HSCT), trisomy, monosomy and age of patients were associated with the prognosis of FUS-ERG group. Unlike pediatric patients, the adult AML1-MTG16 patients did not perform a better outcome (OS: HR = 0.90, P = 0.83; DFS: HR = 0.54, P = 0.34) in contrast with FUS-ERG patients. Conclusions: The retrospective study summarized the clinical characteristics of AML1-MTG16 and FUS-ERG, identifying their distinctions on multiple aspects such as prior disease, recurrence rate, response to chemotherapy and cytogenetics. AML1-MTG16 exhibited extremely bad prognosis like FUS-ERG in adult population, which varied from the results in pediatric cohort. Several factors including age, CR after induction chemotherapy, HSCT, trisomy and monosomy were relevant to the prognosis of FUS-ERG. [Table: see text]
Real-world (RW) use of venetoclax (VEN) in patients (pts) with acute myeloid leukemia (AML) in a US RWE database (COTA).
Authors: Zeidan Amer Methqal , Hernandez Donoso Leyla , Hodzic Sejla , Owusu Henry F , Pathak Dhrubajyoti , Zhou Summera Qiheng , Stein Eytan 
Published: June 2023

7044 Background: VEN + hypomethylating agents (HMAs)/low-dose cytarabine was approved for the treatment (tx) of pts with AML who are ≥75 y or ineligible for intensive chemotherapy (CT) in 11/2018. To understand the use, safety, and efficacy of VEN in clinical practice, the COTA AML database, using pt-level curated electronic health record data from centers across the US, was analyzed. Methods: This is a retrospective, descriptive analysis of deidentified secondary data from the COTA AML database in the US. Data was abstracted for adults diagnosed with AML who initiated first-line (1L) tx on or after 01/01/2018 and received ≥1 VEN tx at any point. Pts with no diagnosis date or with concurrent primary malignancies were excluded. Follow-up was until the last recorded event (last visit or death). The study period for this analysis was 01/2018 to 09/2022. Results: Of 3836 pts with AML in the database, 1163 pts initiated 1L tx in or after 2018; of these, 636 received ≥1 VEN tx at any point. See Table for baseline demographic data. Most VEN-treated pts were seen by community healthcare providers (407/636, 64%). Genetic/molecular data were limited. Of the most frequently tested mutations, the most common were TP53 (129/461, 28%), RUNX1 (109/444, 25%), TET2 (101/414, 24%), ASLX1 (92/417, 22%), and DNMT3A (91/424, 22%). Of pts who received VEN, 47% (299/636) received 1L VEN, and the majority (269/636, 42%) received VEN + HMAs. For pts with tx prior to VEN (pretreated), 262/337 (78%) were previously treated with CT. 1L pts were more often treated in community centers than pretreated pts (73% vs 56%), had more comorbidities (56% vs 40%), and TP53 positivity (19% vs 10%) at baseline. Of 284 VEN-treated pts with available response data, 180 (63%) had a complete response (CR). Median OS (mOS) of VEN-treated pts was 14.4 mo from 1L tx initiation (de novo AML, 17 mo; secondary AML, 14 mo). mOS from diagnosis was 14 mo for newly diagnosed and 18 mo for pretreated pts. Toxicity was the main cause of dose reduction and discontinuation. Median duration of VEN tx was 78 d. Dose reduction was reported in ~30% of VEN-treated pts. Of VEN-treated pts, 53% (338/636) discontinued at least 1 VEN regimen, with a median time to discontinuation of 49.5 d. Conclusions: This study provides an overview of the RW use of VEN in pts with AML in the US since its approval in 11/2018. Despite the study period starting earlier than VEN approval, almost half of pts with AML who initiated tx after 2018 received 1L VEN. The RW CR rate in VEN-treated pts with available data was 63%, but over half of VEN-treated pts had VEN tx discontinuation. [Table: see text]
Preliminary results of a phase 1, first-in-human study of INA03, an anti-CD71 antibody-drug conjugate, in patients with relapsed or refractory (R/R) acute leukemias.
Authors: Garciaz Sylvain , Bories Pierre , Lopez Almeida Leonor , Boher Jean-Marie , Belanger Coralie , Recher Christian , Hermine Olivier , Vey Norbert , Launay Pierre 
Published: June 2023

7045 Background: R/R acute leukemias (AL) represent major therapeutic challenges. Several reports have highlighted the role of iron metabolism in various proliferative tumor models including AL including the over-expression of the transferrin receptor (TfR1/CD71). Our strategy is thus to harness CD71 overexpression to specifically target cytotoxic agents to leukemic cells. INA03 is an antibody drug conjugate (ADC) constituted of a humanized monoclonal IgG4 against CD71 and the microtubule disrupting agent monomethyl auristatin E (MMAE). We herein report the preliminary safety and efficacy data of INA03 from a phase 1/2 trial in patients (pts) with R/R AL (NCT03957915). Methods: INA03 is given as 30 minutes IV infusion on days 1 (Loading dose (LD)) followed by maintenance injections on D15 for cycle 1 and on D1 and D15 of cycle 2 and beyond. Eligibility criteria are: R/R AL after at least one line of treatment including high dose chemotherapy and/or Vidaza and Venetoclax, AlloSCT > 18y, with FEVG > 50%, Creatinine Clearance > 30ml/min, normal liver function, ECOG < 2. The study design is based on a continuous reassessment method and includes 2 parts: a LD Titration study (Part 1, completed), followed by a Dose Escalation Part 2. During Part 1, sequential cohorts of 2 pts were included to receive ascending LD of INA03 followed by subsequent fixed dose of INA03 to deal with a potential sink effect related to the high expression of CD71 in normal erythroblasts. During Part 2, sequential cohorts of 3 pts received escalating doses of INA03 Q2 weeks in 28-day cycles. The objectives were to establish the MTD for subsequent administration and both safety/tolerability and anti-leukemic activity. Results: With a cutoff date of January 18, 2023, 22 pts across 8 cohorts were included in the study. The median age was 73 (range: 39 – 83), 20 (91%) pts had AML and two (9%) had ALL. Three (13.6%) pts had a prior allo-SCT and 12 (54.5%) had prior VEN exposure. Pts received escalating doses of INA03 of 0.02 mg/kg to 2 mg/kg. MMAE pharmacokinetics (PK) appears dose-proportional with a small accumulation after repeated IV, while INA03 PK exhibits target-mediated drug disposition without accumulation. No DLT was observed among the 18 DLT-evaluable pts, up to the highest dose of 2 mg/kg. No grade 2-4 TEAEs were observed. One related grade 1 TEAE (hyperkalemia/phosphatemia) was reported. Transient decrease of reticulocyte count and erythroblasts percentage were observed at 0.5 mg/kg and above. Blasts reductions were seen in 3/18 evaluable pts at dose > 1 mg/kg including two partial responses. Conclusions: INA03 is well tolerated up to the dose of 2 mg/kg with some efficacy signals in R/R AL. The trial continues to accrue patients. Clinical trial information: NCT03957915 .