bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of patients with newly diagnosed acute myeloid leukemia (AML) and hyperleukocytosis.
Authors: Haddad Fadi , Sasaki Koji , Abuasab Tareq , Venugopal Sangeetha , Rivera Daniel , Bazinet Alexandre , Babakhanlou Rodrick , Kim Kunhwa , Senapati Jayastu , Ong Faustine , Desikan Sai Prasad , Short Nicholas James , Pemmaraju Naveen , Borthakur Gautam , Dinardo Courtney Denton , Daver Naval Guastad , Jabbour Elias , Garcia-Manero Guillermo , Ravandi Farhad , Kadia Tapan M. 
Published: June 2022

e19029 Background: Hyperleukocytosis in AML is associated with inferior outcomes. Analyzing the factors associated with mortality in AML patients (pts) with a white blood cell count (WBC) ≥100 x 109/L can guide management and improve early mortality. Methods: We reviewed data from 129 pts with newly diagnosed AML presenting at our institution with WBC ≥100. Logistic regression models estimated odds ratios (OR) for 4-week mortality and Cox proportional hazard models estimated hazard ratios (HR) for overall survival (OS). Results: Median age was 65 years (range 23-86). 66% of pts had ECOG performance status (PS) <2. Median WBC was 146 (range 100-687) and 78 pts had clinical leukostasis (CL) including renal failure in 31 pts (24%), new onset hypoxia in 29 pts (23%), headache in 19 pts (15%), chest pain in 9 pts (7%) and neurological symptoms in 3 pts (2%). 29 pts (22%) had poor cytogenetics. FLT3 and RAS pathway mutations were found in 63% and 27% of pts, respectively. Compared with pts without evidence of CL, pts with CL were less likely to have good PS (ECOG PS <2, 58% vs 82%; P = 0.006), had higher 4-week (16% vs 2%; P = 0.015) and 8-week mortality (19% vs 6%; P = 0.038). Cytoreduction consisted of hydroxyurea in 124 pts (96%), cytarabine in 69 pts (54%) and leukapheresis in 31 pts (24%). Pts who underwent leukapheresis were less likely to receive cytarabine compared with pts who did not (35% vs 59%; P = 0.02); and tended to have more CL compared with pts who did not (74% vs 56%; P = 0.09). 30 pts had tumor lysis syndrome (TLS). TLS risk did not increase with WBC and was not associated with the cytoreductive modality used. 11 pts had intracranial hemorrhage (ICH): 9 pts (82%) with WBC ≥150 and 18% with WBC <150 (P = 0.048). No association was observed between the incidence of ICH and the cytoreductive therapy. 4-week and 8-week mortality rates were 10% and 14%, respectively. After a median follow-up of 49.4 months [mos] (95% CI 26.2-72.6), median OS was 14.3 mos (95% CI 7-21.6), with 2-year OS of 40%. Median OS was 12.3 mos (95% CI 7.4-17.2) compared with 29 mos (95% CI 2.1-55.6) in pts with or without CL, respectively (P = 0.007). Median OS was 9.9 mos (95% CI 7.5-12.2) and 21.3 mos (95% CI 10.7-31.8) among those who did or did not undergo leukapheresis, respectively (P=0.003). Median OS was 42 mos (95% CI 14.2-69.8) compared with 8 ms (95% CI 6-10) in pts < or ≥ 65 years. Conclusions: Older age, poor cytogenetics, TLS and DIC were associated with early mortality and inferior OS in pts with hyperleukocytosis. Careful monitoring of those pts with prompt cytoreduction and management of complications may help improve outcomes. [Table: see text]
Body mass index and venetoclax-hypomethylating agent induction therapy for acute myeloid leukemia.
Authors: Weiss Julian J , Le Henry , Agarwal Sonal , Podoltsev Nikolai Alexandrovich , Zeidan Amer Methqal , Shallis Rory 
Published: June 2022

e19038 Background: Frontline Ven-HMA dosing is imperfectly estimated with HMA using body surface area (BSA) and Ven not BSA/weight-based. Not much is known if elevated body-mass-index (BMI) reduces drug exposure and impacts clinical outcomes with Ven-HMA. We sought to investigate the effectiveness of Ven-HMA in pts with elevated BMI and hypothesized no negative impact on outcomes. Methods: We retrospectively reviewed the records of pts with AML treated with frontline Ven-HMA from 12/2018-11/2021. The primary outcome was composite response rate (CR/CRi) as defined by 2017 ELN criteria. Pearson’s χ2 tests and Wilcoxon rank tests were used for bivariate analyses. Kaplan-Meier methods were used to calculate OS. Results: We identified 63 pts treated with frontline Ven-HMA, among whom 20 had a normal BMI (<25 kg/m2), 27 were overweight (BMI 25-29 kg/m2), and 16 were obese (BMI>30 kg/m2). Median age was 73 (range 37-89) and there were no differences in baseline patient- and disease-specific factors. The cohort overall was enriched for complex karyotype and TP53-mutated disease (46% and 33%, respectively), but without intergroup differences. Increasing BMI was associated with more HMA naivety and appeared to be associated with more antifungal use during induction (BMI <25: 60%, BMI >30: 88%; p=0.07) with similar rates of moderate/strong CYP3A4 inhibition. Early mortality (within 8-weeks of Ven-HMA), was greater in obese pts, but not significantly so (BMI<25: 20%; BMI>30: 31.3%; p=0.45). CR/CRi rate was similar among groups (BMI<25: 40%; BMI 25-29: 52%; BMI>30: 44%; p=0.71), as was ORR ( p=0.14). A sub-analysis excluding pts with prior HMA did not affect the parity in rate of CR/CRi in normal weight or obese pts (40% vs 44%, p=0.83) (Table). Conclusions: Our study showed that increasing BMI appears to have no negative influence on response to frontline Ven-HMA. However, it remains unclear whether increased BMI affects drug exposure, so dedicated studies are needed.[Table: see text]
Outcomes of clostridioides difficile infection in patients with hematopoietic stem cell transplant.
Authors: Mahfouz Ratib , Mansour Mahmoud , Obeidat Adham E. , Darweesh Mohammad , Batayneh Osama , Ghous Ghulam 
Published: June 2022

e19054 Background: Hematopoietic stem cell transplantation (HSCT) recipients are at an increased risk for Clostridioides difficile infections (CDI). Despite it being the main cause of nosocomial enterocolitis in this group of patients, diagnosis of CDI remains challenging and carries significant morbidity and mortality. This is usually due to multiple comorbidities, recurrent antibiotics administration, prolonged immunosuppression, and lengthy hospitalization. This study aims to look more into outcomes and predictors of CDI in HSCT patients in terms of incidence, and mortality. Methods: The United States Nationwide Inpatient Sample was used to extract hospitalization data of patients admitted between 2016 to 2019. Using ICD10 revision codes, we identified adults with a discharge diagnosis of CDI and concomitant HSCT. The control group included non-HSCT patients with CDI. The primary outcome was in-hospital mortality. Secondary outcomes were the length of stay (LOS) and hospital charges. Additionally, predictors for developing CDI and dying from CDI were calculated in HSCT patients. 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 HSCT patients at 4.0% vs. 1.0% in the general population. After adjusting for comorbidities and demographic variables, HSCT was independently associated with increased odds of mortality (adjusted odds ratio [AOR] 1.47 (95%CI 1.20-1.80 and P <0.01). Mean length of stay and hospital charges increased by 1.76 days (95%CI 0.90-2.62, P < 0.01) and $59,023 (95%CI $35,940-$82,105, P < 0.01), respectively, in the HSCT group. In the HSCT group, patients with severe liver disease, malnutrition, and graft vs. host disease showed a significantly higher incidence of CDI. Predictors of mortality of HSCT patients and CDI are outlined in the attached table. Conclusions: HSCT recipients are at an increased risk for CDI compared to general population. LOS, total hospital charge, and mortality rate were significantly higher. The risk of CDI was found to be significantly higher in patients with moderate to severe liver disease, graft vs host disease, and malnutrition. The odds of mortality were found to be the highest in patients older than 65 years and those with congestive heart failure, moderate to severe liver disease, graft vs host disease, or malnutrition.[Table: see text]
Clinical outcomes associated with azacitidine (AZA) monotherapy for treatment-naïve, higher-risk myelodysplastic syndrome (HR-MDS): A systematic literature review and meta-analysis.
Authors: Hasegawa Ken , Wei Andrew H. , Garcia-Manero Guillermo , Daver Naval Guastad , Rajakumaraswamy Nishanthan , Iqbal Shahed , Chan Rebecca J. , Hu Hao , Tse Preston , Yan Jiajun , Zoratti Michael J. , Xie Feng , Sallman David Andrew 
Published: June 2022

e19062 Background: AZA is a standard of care for patients who have HR-MDS. Given the limited availability of large datasets describing outcomes in the current treatment paradigm of HR-MDS, this analysis aimed to aggregate clinical outcomes associated with AZA monotherapy for treatment-naïve HR-MDS. Methods: CENTRAL, EMBASE, and MEDLINE were searched to identify interventional, prospective, and retrospective observational studies in treatment-naïve HR-MDS (defined as intermediate-2 or high risk by IPSS or intermediate to very high risk by IPSS-R) using AZA monotherapy. Inclusion of observational studies was limited to those with n >20 in the AZA arm. Responses according to IWG 2000 or IWG 2006 including complete remission (CR) rate, overall response rate (ORR; defined as CR, marrow CR [mCR], partial response, and hematologic improvement), overall survival (OS), duration of response (DOR), and time to response (TTR) were extracted. Response rates were synthesized using random-effects models; median of medians was used for OS, DOR, and TTR. Results: Of 3250 abstracts identified, 34 publications describing 16 studies met inclusion criteria: 5 randomized controlled trials (RCTs), 3 prospective studies, and 8 retrospective studies. None of the response endpoints were reported in all studies (see Table). The pooled ORR ranged from 44% to 55% across RCTs, prospective, and retrospective studies. The pooled CR rates, reported in 2 RCTs (n=55), 1 prospective study (n=27), and 3 retrospective studies (n=509), were 14%, 11%, and 16%, respectively. The pooled CR rate across all studies (n=591) was 16% (95% CI: 13%, 19%). Pooled median OS (mOS) was 16.7 months (mo) in the 3 RCTs (n=161), 16.5 mo in a single prospective study (n=34), and 14.4 mo in the 5 retrospective studies (n=1472). Pooled mOS across all studies (n=1667) was 16.4 mo (95% CI: 12.0, 17.3). The pooled median DOR was 10.1 mo (95% CI: 9.1, 11.0), and the median TTR was 4.6 mo (95% CI: 3.0, 9.0). Conclusions: These findings provide evidence that benefit from AZA monotherapy in treatment-naïve HR-MDS patients is limited. Opportunity exists for novel therapies to increase response rates, improve the duration of responses, and prolong survival. [Table: see text]
A real-world experience of combined treatment with romidepsin and azacitidine in patients with peripheral T-cell lymphoma.
Authors: Kalac Matko , Tam Constantine Si Lun , Goldfinger Mendel , Xiao Zhengrui , Rajeeve Sridevi , Montanari Francesca , Kanakry Jennifer Ann , O'Connor Owen , Marchi Enrica 
Published: June 2022

e19550 Background: Patients with peripheral T-cell lymphoma (PTCL) lack good treatment options, particularly in the relapsed and refractory setting. Our work suggested that epigenetic therapies can be safe and effective for patients with PTCL, particularly those with T-cell lymphomas with a follicular helper (TFH) phenotype. It is thought that recurrent mutations in epigenetic factors, including Ten-Eleven Translocation-2 (TET2), DNA methyl transferase-3A (DNMT3A) and isocitrate dehydrogenase-2 (IDH2) may contribute to PTLC vulnerability to epigenetic drugs. Methods: Objective of this study was to evaluate the merits of romidepsin plus subcutaneous azacitidine in patients with PTCL when administered in a ‘real-world’ scenario. We retrospectively identified 17 PTCL patients world-wide that were treated with azacitidine and romidepsin outside of a clinical trial based upon queries regarding off study use. The study was reviewed and approved by each Medical Center Institutional Review Board. Their pretreatment characteristics are shown in Table. Results: Eleven patients had angioimmunoblastic lymphoma (AITL), 2 had adult T-cell leukemia/lymphoma (ATLL), 2 had TFH PTCL, 1 had PTCL-NOS and 1 had composite lymphoma (TFH PTCL with diffuse large B cell lymphoma). Ten patients had next generation sequencing performed. Most common mutations found were those of TET2 (7 pts), RHOA (4pts), IDH2 (3pts) and DNMT3A (1 pt). One ATLL patient had mutations in TRAF3, FAT1 and MED12. Among these 17 patients, overall response rate (ORR) was 76% and the complete response rate (CR) was 52%. Median number of cycles was 4 (range 1-12). Treatment was well tolerated but notable adverse effects included nausea, fatigue, rash, neutropenia and thrombocytopenia. One patient experienced febrile neutropenia while another had pulmonary infiltrates (differential diagnosis included drug toxicity versus infection). In 4 patients, azacitidine and romidepsin were used to achieve remission prior to allogeneic transplant (range of cycles 1-3), with all 4 patients were in CR at their last disease assessment. Conclusions: Subcutaneous azacitidine and romidepsin administered in a ‘real-world’ situation is highly effective in patients with relapsed PTCL with tolerable toxicity, and can be used to successfully bridge patients to stem cell transplant.[Table: see text]
Insurance-based disparities in Waldenstrom Macroglobulinemia: An NCDB analysis.
Authors: Chohan Karan , Abeykoon Jithma P. , Ansell Stephen M. , Gertz Morie A. , Kapoor Prashant , Paulus Aneel , Ailawadhi Sikander , Reeder Craig B. , Witzig Thomas E. , Habermann Thomas Matthew , Lacy Martha , Kyle Robert A. , Go Ronald S. , Paludo Jonas 
Published: June 2022

e19562 Background: Considerable healthcare resource utilization and financial burden have been associated with the treatment of Waldenstrom Macroglobulinemia (WM); however, the impact of health insurance status on patient outcomes has not been explored. We aimed to assess the insurance-based outcome relationship in WM using the National Cancer Database (NCDB). Methods: We analyzed patient-level data obtained from the NCDB, a database representing more than 70% of newly diagnosed cancer cases nationwide. All newly diagnosed WM cases (n = 8540) between 2004 to 2017 were identified. Only patients who underwent treatment were included. Insurance status was recorded by assessing the primary payer at the time of diagnosis. Due to Medicare eligibility criteria, age-based (< 65 and ≥65 years) stratified analysis was conducted. Cox proportional hazards model was utilized to analyze survival. Time-to-event analysis was conducted based on date-of-diagnosis using the Kaplan-Meier method and log-rank test. Results: Analysis was conducted on 3878 patients after meeting inclusion criteria, with a median follow-up time of 54.6 months. Among patients < 65 years (n = 1249; median age: 58 years; male: 62.4%), those with non-private insurance had inferior survival on multivariate analysis (Table) after adjusting for patient demographics, comorbidities, income, education, treatment center characteristics, and treatment start time. Significant overall survival (OS) differences were seen in those < 65 years (log-rank p < 0.001), with 5-year OS highest among patients with private insurance 91.2%, compared to Medicaid 79.8%, uninsured 77.4%, and Medicare 70.2%. In patients < 65 years, compared to private insurance, uninsured patients were more likely to be of Black race, reside in lower income areas, and be treated at non-academic centers (all p < 0.05). Both Medicaid and Medicare patients < 65 years were more likely to have a higher Charlson-Deyo comorbidity index (> 1) and live in areas of lower educational attainment and household income compared to private insurance (all p < 0.05). In patients ≥65 years (n = 2629; median age: 75 years; 60.6% males), no insurance-based OS (log-rank p = 0.096) differences were seen. Conclusions: Based on our study, significant insurance-based disparities exist in WM, where patients < 65 years old who are uninsured, or non-privately insured are at a higher risk of mortality. While the root cause of these differences is not fully elucidated, efforts should focus on ensuring that all patients have equal access to care regardless of primary payer status.[Table: see text]
The association between minimal residual disease status and survival outcomes in transplant-ineligible newly diagnosed multiple myeloma (TIE-NDMM) patients: Systematic review.
Authors: Shah Zunairah , Khan Israr , Selene Insija Ilyas , Waqar Syed Hamza Bin , Khanam Razwana , Abid Qurrat-ul-ain , Tahir Nayha , Sathe Sanjivani , Laek Babray , Chattaraj Asmi , Roksana Zinath , Badu Irisha , Anwer Faiz 
Published: June 2022

e20009 Background: Despite expanding therapeutic armamentarium of multiple myeloma (MM), it remains an incurable disease. Therefore, there is a need to assess the impact of deeper hematological responses to better gauge treatments in clinical trials and routine practice. The presence of minimal residual disease (MRD), is becoming crucial and a new standard in monitoring remission status. Clinical evidence shows that MRD status after treatment is an independent prognostic factor for MM. This review summarizes current data on MRD status and its role in predicting progression-free survival (PFS) and overall survival (OS) outcomes. Methods: We performed a literature search on four databases (PubMed, Embase, Cochrane, and Web of Science) following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. We screened 1307 studies using the Mesh terms “Multiple Myeloma and Minimal Residual disease.” After excluding review, duplicate, and non-relevant articles, 7 studies were included. Results: The association between MRD status and outcomes, including survival in TIE-NDMM patients was assessed in 7 studies, including 1083 patients. MRD status was determined using different techniques, such as flow cytometry and clonoSEQ. Different regimens were used in all studies. PFS was reported in all studies. Compared with MRD positive status, achieving MRD negativity improved PFS to 58 months versus 28.65 months as per cumulative analysis. The cumulative OS reported in 2 studies (n=196) was 95.85% in MRD-negative patients compared to 55.65% in MRD positive patients. Conclusions: Further clinical data focusing on post-treatment assessment of MRD will be useful in clinical decision-making and could be practice changing. MRD status may serve as surrogate end-points for PFS and OS in ongoing and future clinical trials. Achieving durable MRD negativity with PFS improvement might also increase the time between treatment relapses for MM and might help switch to a lesser aggressive regimen, chemotherapy-free period, avoiding drug toxicity. [Table: see text]
Comprehensive profiling of the molecular characteristics of both primary tumor and local metastases tumor in Chinese lung cancers.
Authors: Guo Nannan , Jing Zhongying 
Published: June 2022

e20517 Background: Metastasis tumor is the leading cause of lung cancer-related deaths, including local metastasis and distant metastasis. Despite its crucial clinical significance, local metastasis of lung cancer is still largely uncharacterized in terms of underlying molecular mechanisms. Here, we performed TSO500 (Illumina, San Diego, CA, USA) sequencing with 19 matched lung cancer primary and local metastatic samples to comprehensively profiling of lung cancer molecular characteristics. Methods: 19 lung cancer patients with paired primary tumor and local metastatic samples were enrolled, including 16 matched primary-lymph node samples and 3 primary-pleura samples. We compared molecular characteristics, including SNV and TMB, of matched samples. Molecular alterations identified were classified into shared (mutations in both primary and metastases) and private (mutations only in primary or metastases) groups. Thus, share mutation statistical analysis, pathway level enrichment and mutational signature was also done. Results: Comprehensively analysis of matched samples showed that mutational concordance between primary tumor and local metastases is lower. The average rate of concordance of primary-lymph node and primary-pleura was 40.6%±28.4%, 39.0%±33.9% respectively. Obviously, no difference in TMB between local metastases and primary tumor was found, average of primary vs lymph node and primary vs pleura was 7.5 vs 6.5, 6.9 vs 4.2 respectively. Significantly, we found that smoking lung cancer patients have higher TMB compared to non-smokers(p < 0.01), regardless primary tumor or metastatic lymph nodes. Conclusions: Lung cancer has higher inter-tumor heterogeneity with proportion of shared mutations less than 50%. Meanwhile, smoking lung cancer has higher TMB in both primary tumor and metastatic lymph nodes compared to non-smokers.
Study of antitumor activity of 2-quinoline-2-yl-derivative 1,3-tropolone in PDX models of lung cancer.
Authors: Lukbanova Ekaterina A. , Dzhenkova Elena A. , Komarova Ekaterina Fedorovna , Engibaryan Marina A. , Volkova Viktoriya L. , Bauzhadze Mamuka V. , Ulianova Yulia V. , Pustovaya Irina V. , Goncharova Elena G. , Maldonado Mary L. , Chertova Natalia A. , Cherkes Maria A. , Gvaramiya Astanda K. , Khodakova D. V. , Shevchenko Nataliya , Goncharova Anna S. 
Published: June 2022

e20523 Background: The purpose of the study was to reveal the antitumor effect of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone in subcutaneous PDX models of human non-small cell lung cancer (NSCLC). Methods: The studied tropolone was synthesized using a method of expanding the o-quinone cycle. Acute tropolone toxicity was evaluated by the survival and changes in the health status of female Balb/c Nude mice. Antitumor tropolone effects were studied in subcutaneous patient-derived xenograft (PDX) models of human squamous cell lung cancer in Balb/c Nude mice. The average volumes of tumor nodes and tumor growth inhibition (TGI%) rate were taken into account. Biochemical blood tests and histological analysis of the tumor material were performed in recipient mice. Results: An analysis of acute tropolone toxicity did not reveal the lethal dose. The maximal TGI, 73.5% for females and 74.4% for males, was observed on day 36 of the experiment in group 5 which received 2.75 mg/g tropolone. The average tumor volumes in females of this group were 431.3 mm3 on day 33 of the experiment, in males – 428.9 mm3 on day 30, and then the tumor volumes declined. Biochemical blood tests and histological analysis of the tumor material in recipient mice confirmed the tendency demonstrated during the analysis of the TGI dynamics, which in turn was the result of the dose-dependent antitumor effect of the studied tropolone. Conclusions: The research demonstrated the antitumor activity of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone against subcutaneous PDX models of human NSCLC. The revealed tendencies can be used to search for effective modes of the compound application in clinical practice.