bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk, overall survival, and prognostic analysis of therapy-related acute myeloid leukemia in non-Hodgkin lymphoma survivors.
Authors: Joshi Utsav , Gaire Suman , Bhattarai Adheesh , Agrawal Vishakha , Poudyal Bishesh Sharma , Bhatt Vijaya Raj 
Published: June 2022

e19037 Background: Therapy-related acute myeloid leukemia (tAML) is a serious complication in patients with Non-Hodgkin lymphoma (NHL) exposed to chemotherapy or radiation. tAML demonstrates high risk characteristics and poorer outcomes compared with de novo AML. We aimed to quantify the risk of tAML in NHL, determine factors associated with overall survival (OS) in tAML, and compare them with de novo AML. Methods: Patients with a histologic diagnosis of NHL and de novo AML from 2009 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) 18 database. AML that developed at least 1 year after the diagnosis of NHL was classified as tAML. Multiple primary standardized incidence ratio (SIR) sessions of the SEER*Stat software (version 8.3.9) were used to calculate SIR and absolute excess risk (AER) of tAML based on - age, sex, race, year of diagnosis, chemotherapy, radiotherapy, and interval from NHL diagnosis. The 95% confidence intervals (CI) and p-values were generated using multivariate Poisson regression model. OS of both tAML and de novo AML was assessed using Kaplan Meier curves and then compared using log rank test. The roles of various factors on OS in tAML and de novo AML were evaluated using multivariate cox proportional hazard regression. Results: A total of 373 patients with tAML (N for NHL = 301,903) and 23,360 patients with de novo AML were included in the analysis. More de novo AML cases were ≥70 years compared to tAML (41.1% vs 32.7%, p < 0.001). The risk of development of tAML was significantly higher in ages < 60 years compared to 60-69 years and ≥70 years (SIR 14.0, 95% confidence interval [CI] 11.79-16.51 vs SIR 4.87, 95% CI 4.00-5.86 vs SIR 2.80, 95% CI 2.32-3.34, p < 0.0001). Patients who received chemotherapy were more likely to develop tAML than the non- recipients (SIR 8.44, 95% CI 7.51-9.44 vs SIR 1.75, 95% CI 1.37-2.21, p < 0.0001). The risk of tAML was higher within 5 years of NHL diagnosis (SIR 5.05, 95% CI 4.49-5.67 vs SIR 4.39, 95% CI 3.49-5.45, p < 0.001). There was no statistically significant difference in SIR based on sex, race, receipt of radiotherapy, and year of diagnosis. The median OS and 5-year OS were- 8 months and 13.1% for tAML and 10 months and 27.6% for de novo AML. On multivariate analysis, tAML was not found to be an independent predictor of OS (HR 0.93, 95% CI 0.82-1.04, p = 0.21). Age ≥60 years (age 60-69 years: HR 1.53, 95% CI 1.08-2.15, p = 0.01, age ≥70 years: HR 1.93, 95% CI 1.40-2.66, p < 0.001) and no chemotherapy (HR 1.82, 95% CI 1.40-2.35, p < 0.001) were associated with poor OS in tAML subcategory. Conclusions: Our large population-based study shows increased risk of tAML within the first 5 years of NHL diagnosis, younger NHL survivors, and chemotherapy recipients. Older age and no chemotherapy predispose to dismal OS in tAML.
Non-variceal upper gastrointestinal bleeding in patients with acute leukemia.
Authors: Mansour Mahmoud , Obeidat Adham E. , Abu-Farsakh Yomna , Mahfouz Ratib , Darweesh Mohammad , Ghous Ghulam , Tahan Veysel 
Published: June 2022

e19041 Background: Patients with acute leukemia are prone to various hemorrhages, most frequently due to thrombocytopenia from disease activity or chemotherapy. However, there is minimal literature evaluating non-variceal upper gastrointestinal bleeding (NVUGIB) in leukemia patients. This study evaluates the outcomes of NVUGIB in hospitalized acute leukemia patients. 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 NVUGIB and a concomitant acute leukemia diagnosis, acute myelogenous leukemia and acute lymphoblastic leukemia. The control group included non-leukemia patients with NVUGIB. Primary outcome was in-hospital mortality. Secondary outcomes were length of stay (LOS), hospital charges, and effect of early esophagogastroduodenoscopy (EGD) within the first 24 hours of admission. Multivariate logistic regression was used to adjust for comorbidities and demographic variables. Results: A total of 1,208,885 discharges were identified with NVUGIB. Of those, 1019 had acute leukemia. Leukemia patients had higher mortality than the general population (12.5% vs. 3%, respectively; P <0.01). After adjusting for comorbidities and demographic variables, acute leukemia patients had significantly higher mortality (adjusted odds ratio [AOR] 3.75, 95%CI 2.37-5.94 P <0.01). Mean length of stay and hospital charges increased by 6.87 days (95%CI 3.99-9.75, P < 0.01) and 128,437$ (95%CI 68,633$-188,240$, P < 0.01), respectively, in the acute leukemia group. Additionally, acute leukemia patients who had an early EGD had significantly less mortality, length of stay, and hospital charges compared to delayed EGD as shown in the attached table. Conclusions: Acute leukemia patients admitted with NVUGIB have significantly higher in-hospital mortality and health care burden. Early EGD in these patients is associated with lower in-hospital mortality, shorter length of stay, and lower total hospital costs. However, given the retrospective nature of this study, we cannot determine that early EGD is a causal factor for the improved outcomes. Future prospective studies will be required in acute leukemia patients admitted with NVUGIB to further evaluate these findings.[Table: see text]
A national inpatient sample analysis for CAR-T cell therapy administration.
Authors: Bakalov Veli , Tang Amy , Helfand Alexander M , Kancharla Pragnan , White Richard , Khattab Ahmed , Alhousani Mohammad , Samhouri Yazan 
Published: June 2022

e19501 Background: Chimeric antigen receptor T-cell therapies (CAR-T) improve relapse free survival and durable remission rates in patients with relapsed/refractory large B-cell lymphoma (LBCL) and received US FDA approval in 2017. The cytokine release syndrome (CRS) and immune-effector cell associated neurotoxicity (ICANS) due to CAR-T cell therapy require close inpatient monitoring. Real world data are lacking regarding the cost of hospitalization, length of stay (LOS), toxicity, and mortality associated with CAR-T. The goal of this study was to analyze the clinical outcomes of inpatient CAR-T utilizing a national database. Methods: Data was collected from the 2018 version of the Nationwide Inpatient Sample (NIS) database. Patients who received CAR-T were identified with ICD-10 disease and procedure codes . Complex weights were used to enable appropriate national projections. The association between toxicity (particularly related to CRS and ICANS) and outcomes was examined using logistic regression analyses (p < 0.05 statistically significant). SAS v9.4 (SAS Institute, Cary, NC) was used for data analysis. Results: 306 patients met selection criteria. Demographic criteria were as follows: 61.1% males, 62.4% white, median age 58.0 years old (IQR 45.2-65.0), and private insurance (56.9%). A majority received care at urban teaching (97.7%) and large hospitals (73.2%). Relevant complications during hospitalization included hypotension (24.5%), pneumonia (8.5%), sepsis (9.8%), seizure (5.9%), neutropenia (24.5%), thrombocytopenia (8.8%), tumor lysis syndrome (TLS) (3.3%), and acute kidney injury (AKI) (14.1%). Median LOS was 16 days (IQR 12.0-22.0), median charge for hospitalization was $493,887 USD (IQR 143,400.0-1,182,940.0), and inpatient mortality was 5.2%. On multivariate regression analysis, inpatient mortality was significantly higher in those with intubation (OR 30.1, 95%CI 3.45-262), sepsis (OR 9.49, 95%CI 1.48-60.7), TLS (OR 18.9, 95%CI 2.52-140), AKI (OR 24.7, 95% CI 1.37-447) and thrombocytopenia (OR 53.4, 95% CI 2.19-1,298). LOS was higher in those with blood transfusion (OR 1.29, 95% CI 1.08-1.53), sepsis (OR 2.04, 95% CI 1.59-2.61), pancreatitis (OR 2.03, 95% CI 1.09-3.77), pneumonia (OR 1.39, 95%CI 1.04-1.87) and treatment in urban teaching hospitals (OR 1.53, 95%CI 1.02-2.30). Increased hospitalization charges were associated with hypotension (OR 1.54, 95%CI 1.14-2.08) and with treatment at urban teaching hospitals (OR 7.46, 95%CI 4.67-11.9) and medium size hospitals (OR 1.49, 95%CI 1.04-2.15). Conclusions: Inpatient mortality, median LOS, and hospitalization charges in inpatients treated with CAR-T can be significantly increased not only by inpatient complications, but also by the size and type of the treating facility. These findings highlight the financial burden of CAR-T cell therapy in the real world and can be used to shape future healthcare policy.
A sensitive and robust bioanalytical assay for pharmacokinetic analysis of ROR1xCD3 bispecific T cell engager (NVG-111) in a first-in-human study.
Authors: Shah Mittal , Granger David , Bobrzynski Tomasz , Baccaro Annalisa , Gore Jasmine , Muczynski Vincent , Cook Sarah , Chester Kerry , Batten Toby , O'Donovan Kieran , Jasani Parag , Nathwani Amit C. 
Published: June 2022

e19505 Background: Receptor tyrosine kinase-like Orphan Receptor-1 (ROR1) is widely expressed on hematological and solid tumors. NVG-111, a first in class humanized tandem scFv ROR1xCD3 bispecific antibody elicits potent killing of ROR1+ tumor cells in vitro and in vivo. This bispecific T-cell engager (TCE) is being evaluated in a first in human, Phase I trial in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). The predicted therapeutic dose and steady state serum concentrations of NVG-111 were estimated by allometric scaling using relevant doses from a murine PK study. To assess free drug levels in patients following 21 days of continuous infusion of NVG-111, a bespoke, sensitive pharmacokinetics (PK) assay with high levels of specificity and sensitivity was developed. Methods: Anti-idiotype (anti-ID) antibodies directed to anti-ROR1 (αROR1-ID) and anti-CD3 (αCD3-ID) were generated by mouse immunization or by phage display from customized libraries. A proof-of-concept sandwich ELISA assay was developed using αCD3-ID to capture NVG-111 and detection by biotinylated hROR1-streptavidin-HRP. Gyrolab and Quanterix Simoa high sensitivity ELISA platforms were used to detect NVG-111 by αCD3-ID capture and αROR1-ID detection. The mesoscale discovery electrochemiluminescence assay (MSD-ECLA) was developed using a reversed format; NVG-111 capture with αROR1-ID and detection with αCD3-ID. Results: Allometric scaling predicted a theoretically relevant therapeutic dose and steady state serum concentration of 1ng/mL NVG-111 in humans, which was just at the level of sensitivity of a conventional ELISA under non-matrix conditions. Transferring the format to Quanterix Simoa had limited success due to high background levels in all configurations evaluated. The Gyrolab platform increased sensitivity to 75pg/mL, but suboptimal individual human sera matrix selectivity limited assay validity. Assessment of MSD-ECLA provided the best signal/noise, enhanced human disease and healthy sera selectivity, and a dynamic sensitivity range of 250pg/mL to 32ng/mL, which enabled the development of a GCLP qualified PK assay. The MSD-ECLA assay was employed to measure NVG-111 concentrations in CLL or MCL subjects dosed with 0.3-30µg/day NVG-111. MSD-ECLA detected drug in patients receiving NVG-111, with a range of steady-state serum concentrations (Cavg.ss) of 168-610pg/mL. This was in-line with the predicted drug levels from the single species allometric scaling, albeit with observed levels being marginally lower than expected. Conclusions: Development, custom optimization and validation of a highly sensitive MSD-ECLA PK assay has enabled GCLP-compliant measurement of circulating NVG-111 in CLL or MCL patients treated with at least 10µg/day cIV NVG-111.
Survival trends among patients diagnosed with both melanoma and chronic lymphocytic leukemia.
Authors: Zhao Yayi , Amorrortu Rossybelle , Stewart Sandra C. , Ghia Kavita , Williams Vonetta L. , Sondak Vernon K. , Tsai Kenneth Yee , Pinilla-Ibarz Javier , Chavez Julio C. , Rollison Dana Elise 
Published: June 2022

e19527 Background: Patients previously diagnosed with melanoma have a higher risk of developing subsequent chronic lymphocytic leukemia (CLL). Similarly, melanoma risk has been observed to be elevated among patients with a history of CLL. However, previous studies have reported inconsistent results on whether being diagnosed with both cancers significantly reduces patient survival. Additional research is needed to assess the potential reduction in survival among this unique cohort of patients diagnosed with both melanoma and CLL. In addition, the timing of the cancer development needs to be assessed to further explore unique patient characteristics. Methods: A retrospective cohort study was conducted using data from adult patients who were diagnosed and/or treated for melanoma (n = 5,511) or chronic lymphocytic leukemia (CLL, n = 571) at Moffitt Cancer Center (MCC) in 2008-2020. Clinical characteristics and survival information were obtained from the MCC Cancer Registry including, date of diagnosis, vital status, time of death or last contact, and tumor stage at diagnosis. The Kaplan-Meier method was used to estimate survival for three patient groups: patients diagnosed with only melanoma, patients diagnosed with only CLL, and patients who were diagnosed with both cancers. The timing of the two cancer diagnoses were assessed among the 17 patients diagnosed with both melanoma and CLL. Results: The estimated 5-year survival was 78.5% and 82.9% among patients diagnosed with only melanoma and only CLL, respectively. Among patients who were diagnosed with both cancers, the 5-year survival since melanoma diagnosis was 61.4% whereas the 5-year survival since the CLL diagnosis further reduced to 60.2%. When analyzing the timing of the diagnoses of the two cancers, 13 out of 17 patients were diagnosed with melanoma prior to CLL. Further, among these 13 patients, 12 patients had CLL diagnosed within 100 days after the melanoma diagnosis. Conclusions: Patients diagnosed with both melanoma and CLL experienced poorer survival outcomes as compared to patients who were diagnosed with only one of these cancers. Among patients who were diagnosed with both cancers, more than 70% of the patients were diagnosed with CLL shortly after their melanoma diagnosis. Additional research using larger national cancer registry databases can help to advance the understanding of the underlying disease mechanism and confirm the observed timing of diagnoses is due to the CLL being diagnosed incidentally as result of node biopsies for melanoma.
Clinical characteristics and outcomes of newly diagnosed patients with human immunodeficiency virus-associated lymphoma administered highly active antiretroviral therapy: Central and Western China AIDS Lymphoma League 001 study (cw-CALL 001).
Authors: Wang Chaoyu , Liu Jun , Lei Haike , Wu Yongzhong , Liu Yao 
Published: June 2022

e19535 Background: HIV-associated lymphoma is the most common subtype of HIV-associated cancers, with a very low incidence. To date, there are only few retrospective studies analyzing the clinical features and prognosis of HIV-associated lymphoma. Therefore, we performed a study to analyze the clinical characteristics and outcomes of newly diagnosed HIV-associated lymphoma patients in our center, as the largest HIV-associated lymphoma cohort in China so far. Methods: Totally 107 newly diagnosed HIV-associated lymphoma patients in Chongqing University Cancer Hospital, Southwest China, from July 2008 to August 2021, were analyzed. Results: In the 107 HIV-associated lymphoma cases, median age was 49 years (range: 23–87 years), and more patients were male (87.9%). Most patients had elevated lactate dehydrogenase (LDH) (78.5%), elevated β2-MG (91.6%), advanced Ann Arbor stage (73.8%) and high IPI score (IPI score: 3-5) (62.7%) at diagnosis. Totally 46 patients (43%) had one or more sites of extranodal involvement, of whom 24 (22.4%) possessed two or more extranodal sites. Median CD4+ T cell count at diagnosis was 191/μl (range: 4-1022); 84 patients (78.5%) were on combination antiretroviral therapy (cART) at lymphoma diagnosis. Of the 72 patients evaluated at the end of treatment, the overall response rate (ORR) was 81.9% (59/72); 29 (40.3%) cases achieved complete response (CR), 30 (41.7%) had partial response (PR) and 9 (12.5%) experienced progressive disease (PD). In 99 HIV-associated lymphoma cases with complete follow-up data (median follow-up of 44.5 months [range: 2-160 months]), median PFS and OS were 36.0 months and not reached, respectively. The overall 5-year PFS and OS rates were 46.9% and 53.4%, respectively. Compared with individuals not administered anti-lymphoma treatment or administered less than 3 cycles anti-lymphoma therapy, those who received standardized anti-lymphoma therapy (≥3 cycles) showed improved PFS ( p=0.0006) and OS ( p<0.0001). In patients administered systemic anti-lymphoma therapy, the overall 2-year PFS rates for chemotherapy and R-chemotherapy were 29.5% and 67.1%, respectively (HR=0.44, 95%CI 0.210-0.927; p=0.020). The overall 2-year OS rates for chemotherapy and R-chemotherapy were 51.9% and 73.1%, respectively (HR=0.42, 95%CI 0.183-0.969; p=0.042). Conclusions: Overall, these data indicated that HIV-associated lymphoma has aggressive characteristics, including advanced Ann Arbor stage, high IPI score, more extranodal involvement and elevated LDH. Survival is significantly improved due to the wide use of cART and chemoimmunotherapy. Standardized anti-lymphoma therapy is significantly associated with superior outcomes. Clinical trial information: ChiCTR2100054581.
Clinicopathological features and management of patients with primary CNS lymphoma: Peruvian experience in two cancer centers.
Authors: Castro-Mollo Melanie Wendy , Diaz Alonso , Roque Perez Katia , Meza Jessica Gabriela , Quintana Truyenque Shirley Milenca , Peña Estefanía , Lopez Lourdes , Barrionuevo Carlos , Mallma Soto Víctor Iván , Dueñas Daniela , Alcarraz Cindy Elizabeth , Vidaurre Tatiana , Samanez Cesar Augusto , Vasquez Jule F 
Published: June 2022

e19541 Background: Primary central nervous system lymphoma (PCNSL) is an aggressive and rare extranodal non-Hodgkin lymphoma with a dismal prognosis in most patients. Outcomes in Latin population is unknown. Methods: We present a retrospective cohort of fifty-five and six newly diagnosed Peruvian patients treated at the Instituto Nacional de Enfermedades Neoplasicas from 2000-2020 and at Oncosalud from 2014-2020, respectively. Inclusion criteria were (1) histologic diagnosis of diffuse large B-cell lymphoma by two pathologists; (2) disease localized exclusively in the brain, cranial nerves, meninges, or eyes; and (3) no evidence of human immunodeficiency virus infection. Results: Median age at diagnosis was 52 years old [range 21-76]. Sixty-one percent were men. Eastern Cooperative Oncology Group performance status was ≥2 in 68% of patients. Clinical presentation was characterized by intracranial hypertension symptoms (67%), focal deficit (64%), visual disturbance (18%), and seizures (9%). elevated LDH was present in 26/46 (57%) patients, multiple lesions in 19/56 (34%) patients, and involvement of deep structures 21/62 (34%) patients. Seven patients were treated by surgery only (3, subtotal and 4, total resection), three patients received radiotherapy only, and six patients did not receive any treatment. Forty-two patients received the following chemotherapy protocols: DeAngelis (26%), high-dose methotrexate (HD-MTX) (17%), HD-MTX + high-dose ARAC (HD-ARAC) (36%) and HD- MTX + HD-ARAC + Rituximab (9%), HD-MTX + Rituximab + Temozolomide (TMZ) as induction and consolidation with etoposide (VP16) + HD-ARAC (12%), the latter was used in the private center. Clinical outcomes are described in Table. The median follow-up time was 9m (0.03-248). The median overall survival (OS) was 9.9m, 5y OS was 41.7% (95% CI, 29.2-53.9). The median OS were 6.6m and 67.3m for the public and the private institution, respectively (p=0.02). 5y OS was 34% and 100% in the public and the private center, respectively. Conclusions: Peruvian patients are 15 years younger than those reported in the literature. OS in our cohort is dismal, being poorer in those patients treated at the public center reflecting treatment disparities between the public and private health system. All patients who received HD-MTX+HD-ARAC+TMZ as induction and VP16 +HD-ARAC as consolidation achieved complete response and the median OS was not reached although this can be explained due to a short follow-up time compared to those who received DeAngelis regimen. A longer follow-up is needed to demonstrate if polychemotherapy without radiotherapy is the best treatment in this group of patients.[Table: see text]
Patient preferences for second-line treatment options in diffuse large B-cell lymphoma: A discrete choice experiment.
Authors: Birch Kelly , Chiu Kevin , Baumgardner James , Snider Julia , Wade Sally West , Shah Gunjan L. 
Published: June 2022

e19558 Background: Standard of care (SOC) treatment in second-line (2L) large B-cell lymphoma (LBCL), including diffuse LBCL (DLBCL), involves salvage chemotherapy followed by autologous hematopoietic cell transplant (AHCT) for those with chemo-sensitive disease. However, many patients do not respond adequately to chemotherapy or are otherwise ineligible for AHCT. Chimeric antigen receptor T-cell (CAR T) therapy is a promising 2L therapy for LBCL that differs from SOC agents in terms of mechanism of action, therapeutic benefit, and safety profile. Given these differences, this discrete choice experiment (DCE) quantified 2L treatment preferences among patients with DLBCL. Methods: We conducted an online DCE with patients with DLBCL residing in the United States (US) and Europe (United Kingdom, France, Italy, Germany, and Spain). Attributes of 2L treatments were parameterized based on clinical trial data and included the probability (percent of patients) of surviving one year after treatment, the change in survival rate from one to three years, the risks of severe cytokine release syndrome (CRS) and neurological events, the risk of severe infection, and expected time until the patient’s functioning would return to pre-treatment levels. A willingness-to-accept measure was used to assess how much of an increase in one-year survival was needed for a patient to accept elevated risks of severe CRS and neurological events, which can be associated with CAR T treatment. Results: A total of 224 patients were included in the analysis (US: 105; Europe: 119). The mean age of respondents was 50 years (range 34 - 76); 74% were male, and 94% were actively receiving cancer treatment. Patients considered the probability of surviving one year after treatment to be the most influential treatment attribute, followed by risk of severe CRS/neurological events. The third most influential attribute was the change in probability of survival for three years post-treatment for US patients and time needed to return to pre-treatment functioning for European patients. The willingness-to-accept calculation found that patients required a 13-14 percentage point increase in the probability of surviving one year to accept a 28% risk of a serious neurological event and a 13% risk of serious CRS. Conclusions: Patients with DLBCL showed their willingness to accept increased risks of CRS and neurological events to achieve a greater probability of survival. This preference tradeoff (efficacy over risk of adverse events) has been shown previously for lymphoma patients. Patients also valued a quicker return to baseline functioning, which is notable given recent data on the quicker recovery of quality of life with CAR T compared with SOC. These patient preferences provide important context for 2L LBCL treatment decisions, and may lead to shared decision-making that reflects both clinical and patient priorities.