bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical characteristics and outcomes of cancer patients with chronic kidney disease and coronavirus disease 2019.
Authors: Mamlouk Omar , Turin Anastasia , D'Achiardi David , Simbaqueba Cesar , Dickson Kodwo , Franco-Vega Maria , Halm Josiah , Mandayam Sreedhar ,   D3CODE Team
Published: June 2021

e18815 Background: Coronavirus disease 2019 (COVID-19) has been associated with higher risk of acute kidney injury (AKI) and mortality rate in cancer patients. The prevalence of CKD in cancer patients is close to 20-30% however there has been limited data about cancer patients with CKD and COVID-19 infection. The aim of this study is to evaluate the clinical characteristics and outcomes of this patient population at a tertiary cancer center. Methods: All patient data — demographics, labs, comorbidities and outcomes — were aggregated and analyzed in the Syntropy platform, Palantir Foundry (“Foundry”), as part of the Data-Driven Determinants of COVID-19 Oncology Discovery Effort (D3CODE) protocol at MD Anderson. The cohort was defined by the following: (1) positive COVID-19 test; (2) baseline eGFR 15-59 ml/min/1.73m2 calculated by chronic kidney disease epidemiology collaboration equation. The baseline GFR and creatinine values used the most temporally proximal lab results within 30 days prior to the patient’s infection. AKI was defined as an absolute change of creatinine ≥0.3 mg/dl above the baseline after the positive COVID-19 test. Results: Out of 790 patients with COVID-19,19.6% had underlying CKD. Among these, 86.5% and 46.5% had history of hypertension and diabetes mellitus, respectively. 77.3% had a solid malignancy and 87.3% of them had metastatic disease. 67.7% were asymptomatic, 14.2% required ICU admission, 10.3% required invasive ventilation support, and 11.6% died within 90 days of the COVID-19 test. AKI developed within the first 30 days in 61.3% and 8.4% required renal replacement therapy. AKI was more prevalent in patients who were hospitalized (84.2% vs. 31.7%, p< 0.001), had concurrent pneumonia (63.3% vs. 36.8%, p< 0.002), required critical care (68.3% vs. 15.8% , p< 0.001), and were on ventilation support (16.8% vs. 0%, p=0.002). There was no significant statistical difference in rates of diabetes (52.6% vs. 36.7%, P of 0.076), tumor staging (metastasis; 95.1% vs. non metastatic 82.6%, p< 0.2) , readmission rate (52.6% vs. 43.3%, p=0.336), and death rate at 30 days (9.5% vs. 3.3%, p=0.205) between the two groups. Conclusions: The overall mortality rate of cancer patients with CKD and positive COVID-19 test was relatively high and close to 1.7 times the rate of patients with no CKD at our tertiary cancer center. AKI is a common complication in CKD patients with concurrent pneumonia and requiring ventilation support, and was associated with increased morality at 90 days.
Impact of cancer- and patient-level factors on provider risk in the Oncology Care Model.
Authors: Chaudhry Basit Iqbal , Yue Andrew , Kaila Shuchita , Sadik Kay , Tran Lisa , Connor Nora 
Published: June 2021

e18852 Background: Transferring financial risk from payers to providers to align incentives is central to value-based payment (VBP) reform, including Medicare’s Oncology Care Model (OCM). We simulated the impact of selected cancer- and patient-level factors on providers’ risk in OCM for multiple myeloma (MM), due to its clinical complexity. We hypothesize that risk exposure is sensitive to factors extrinsic to the OCM methodology, including clinical phenotype, disease state and progression rate. Methods: Simulation was used to address omitted variable bias in payer data. We developed 9 key clinical MM scenarios to examine provider risk, based on conceptual frameworks that included patient- and cancer-level factors. The model was parameterized using the Medicare limited data set, research literature and domain knowledge. Twenty factors were varied for each model, e.g. age, autologous stem cell transplant (ASCT). Results: Simulations results showed MM risk for providers depended highly on cancer and patient level factors (see table). For example, high-risk patients were on average $21.5K over target while undergoing ASCT (despite risk adjustment for ASCT) and $18-28K under target for follow on maintenance (maint.) episodes. Conclusions: Provider exposure to risk in OCM is highly sensitive to factors at the cancer and patient level. The distribution of clinical phenotypes, state of disease, and rate of disease progression can significantly impact risk exposure for providers in OCM. New methodologies that model risk in more clinically granular ways are needed to improve VBP in oncology. [Table: see text]
Assessing the use of low value oncology care following the release of Choosing Wisely guidelines.
Authors: Gunn Alexander , Sarver Melissa , Kaplan Samantha J , Zafar Yousuf , Greenup Rachel Adams 
Published: June 2021

e18861 Background: Low -value care contributes to the high costs of cancer treatment. Almost a decade has passed since the American Society of Clinical Oncology (ASCO) Choosing Wisely campaign identified costly diagnostic testing, radiographic imaging, and therapies that are routinely utilized in cancer care despite lacking evidence of benefit. We sought to evaluate the impact of ASCO Choosing Wisely guidelines and to identify barriers to and facilitators of guideline adherence. Methods: A systematic review of published literature from 2012-2021 was performed in accordance with PRISMA guidelines on the trend in use of low value oncology care. All ten of ASCO Choosing Wisely Guidelines were selected for inclusion; these included recommendations focused on cancer screening, staging and surveillance imaging, and systemic treatment and support. The following databases were searched for original research based in the United States: PubMed, CINAHL, Embase, Web of Science, Scopus, and ASCO Meeting abstracts. Eligible studies were examined for information on design, population, and study outcomes, which included guideline adherence and facilitators and barriers to implementation. All citations were independently dual-screened in a blinded fashion by authors (AG, MS). Results: 35 independent studies were identified from 3,590 unique citations and included n = 1,130,216 patients. Data sources captured large claims database analyses (13 studies, n = 1,069,289), institutional studies (14 studies, n = 53,358), patient-reported surveys (2 studies, n = 915), and interventional studies (6 studies, n = 6654). Adherence to ASCO Choosing Wisely guidelines ranged from 13% to 100% overall. Use of low value oncology care varied depending on the area of recommendation, such as cancer screening (44% to 77%), staging and surveillance imaging (30% to 100%), and systemic treatment and support (13% to 100%). Adherence was facilitated by: (a) physician awareness of and education around the recommendations; (b) patient engagement; (c) embedded EHR best practice alerts; (d) guideline alignment with insurance payer requirements; and (e) integrated healthcare systems. Barriers to guideline incorporation included perceived patient anxiety and concerns about patient satisfaction; illness-specific practices; and time needed for patient-provider conversations regarding low value care. Conclusions: Adherence to the ASCO Choosing Wisely guidelines is variable across the cancer care continuum. Health system and policy-level interventions are needed to further reduce the overuse of low value care in oncology.
A national study of allogeneic stem cell transplantation for adults with acute myeloid leukemia: Do gender and age above 70 years matter?
Authors: Emole Josephine , Shune Leyla , Lupak Oleksandra , Dias Ajoy Lawrence 
Published: June 2021

e19020 Background: Allogeneic stem cell transplantation (alloSCT) is increasingly being offered to older patients with acute myeloid leukemia (AML) due to availability of reduced-intensity conditioning regimens and better supportive care. Though studies have shown improving alloSCT survival outcomes in older age groups, it is still not known if older age confers higher mortality and morbidity during transplant hospitalization. We queried a national inpatient database to evaluate in-hospital mortality and resource utilization during alloSCT for AML in patients >70 years compared to a younger age group. Methods: We conducted a retrospective study of alloSCT for AML patients ≥ 18 years using the 2018 National Inpatient Sample database. Hospitalizations were selected using International Classification of Disease, tenth revision (ICD-10) codes. Demographics, comorbidities, transplant, and outcome variables were compared between a reference age group (18-70 years) and a comparator group (> 70 years). Study outcomes were in-hospital mortality, length of stay (LOS) and transplant complications. Regression models were fit to assess the association between predictors and outcomes. Results: During the study period, 2610 alloSCT met the inclusion criteria. This cohort consisted of 50% males and 77% Caucasians. Only 7% of these alloSCT were performed for patients > 70 years. Patients >70 yrs had a lower proportion of females compared to the reference age group (32% versus 52%, p<0.01). There were no significant differences in racial distribution, Charlson comorbidity index or median income between the 2 age groups. In-hospital mortality rates for the reference age group versus >70 years were 3% and 5% respectively (p=0.35). In a multivariable model, we found no association between age >70 years and in-hospital transplant mortality. Acute graft versus host disease was more frequent among the reference age group (14% versus 2%, p=0.04), but there were no differences in LOS or rates of graft failure, respiratory failure, sepsis, and acute renal failure between the 2 groups. Conclusions: Despite similar in-hospital transplant outcomes as their younger counterparts, patients >70 years comprised only a small proportion of alloSCT performed for AML in our study. Females were more disproportionately affected by this age disparity. More studies are necessary to identify barriers to alloSCT for older AML patients, more so for older females.
Prognostic value of BCL2 and TP53 genetic alterations for diffuse large B-cell lymphoma treated with R-CHOP.
Authors: Qin Yan , Chen Haizhu , Liu Peng , Zhang Changgong , Yang Jianliang , Gui Lin , He Xiaohui , Zhou Liqiang , Zhou Shengyu , Jiang Shiyu , Jiang Hongxin , Shi Yuankai 
Published: June 2021

e19549 Background: Unlike BCL2 translocation ( BCL2TR), limited data about the prognostic significance of BCL2 mutations ( BCL2MUT) and BCL2 copy number variations in diffuse large B-cell lymphoma (DLBCL) is available, especially in the era of immunochemotherapy. Predicting outcomes at the time of diagnosis is of extreme importance. Methods: In this study, we performed probe capture-based high resolution sequencing on 191 Chinese patients with de novo DLBCL, attempting to comprehensively describe BCL2 genetic alterations and several other genes. We also examined correlation between genetic alterations and outcomes in 164 patients treated with R-CHOP. BCL2, MYC and BCL6 protein was determined by immunochemistry. Results: Of all the 191 patients, BCL2 gain/amplificatio n ( BCL2GA/AMP) and BCL2MUT occurred in 9.4% and 8.9% of patients, respectively, and only 4.2% of cases harbored BCL2TR. As a result, BCL2 alteration, comprised of the above three genetic alterations, was observed in 18.3% of patients. Compared to patients with the absence of BCL2 alteration, the 5-year progression-free survival (PFS) (13.7% vs 40.8%, P= 0.003) and overall survival (OS) (34.0% vs 70.9%, P= 0.036) were significantly inferior in cases that harbored BCL2 alteration. Importantly, patients who harbored BCL2GA/AMP also had remarkably inferior PFS (5-year PFS, 11.1% vs 38.3%, P< 0.001) and OS (5-year OS, 22.1% vs 69.6%, P= 0.009) compared to those without BCL2GA/AMP. By contrast, neither BCL2MUT nor BCL2TR were significantly prognostic for survival. Multivariate analysis showed that the presence of BCL2 alterations, especially BCL2GA/AMP, TP53 mutation and International Prognostic Index (IPI) were significantly associated with inferior PFS and OS. Novel prognostic models were constructed based on 3 risk factors, including BCL2 alteration (Model 1) or BCL2GA/AMP (Model 2), TP53 mutation and IPI, stratifying patients into three risk groups with different outcomes. According to Model 1, the 5-year PFS were 65.9%, 25.9%, and 12.9% ( P< 0.001), and 5-year OS were 89.4%, 65.0% and 16.4% ( P< 0.001), respectively, for the low-risk, intermediate-risk and high-risk groups. In Model 2, the 5-year PFS was 56.9% for the low-risk, 24.1% for the intermediate-risk and 14.3% for the high-risk group ( P< 0.001), and 5-year OS were 86.6%, 60.9% and 16.9% for the three risk groups ( P< 0.001), respectively. Conclusions: This study demonstrated that, in patients treated with R-CHOP, the presence of BCL2 alteration, especially BCL2GA/AMP, and TP53 mutation were significantly associated with inferior outcomes independent of IPI. The novel prognostic models we proposed could aid in individual risk prediction for DLBCL patients treated with R-CHOP. Further validation of this prognostic model is warranted.
Prognostic biomarkers for primary Sjögren's syndrome-associated non-Hodgkin's lymphoma.
Authors: Ma Kevin Sheng-Kai , Velarde Lopez Angel Alfonso 
Published: June 2021

e19563 Background: Bidirectional relationship between non-Hodgkin’s lymphoma (NHL) and Sjögren’s syndrome (SS) has been recognized in large-scale cohort studies. We identified significant differentially expressed genes for SS-associated NHLs, and evaluated whether these genes could serve as a prognostic biomarker of diffuse large B-cell lymphoma (DLBCL). Methods: RNA-sequencing data from whole-transcriptome expression profiling were compared in a canonical pathway analysis using z-score and p-value visualization to identify significant differentially expressed genes and underlying cellular mechanisms for SS-associated NHLs including Burkitt lymphoma (BL), DLBCL, follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL). Collected biopsies included lymphoma biopsies for BL (n = 59), DLBCL (n = 88), FL (n = 65), MCL (n = 43), and MZL (n = 23), sorted B cells from healthy donors (n = 10), as well as parotid gland tissues for SS (n = 17). RNA-seq data with P values less than 0.05 or -log10(P) larger than 1.3 were considered significant, and positive z-scores indicated up-regulation while negative z-scores indicated down-regulation. After screening potential biomarkers through canonical pathway analysis, significant differentially expressed genes were subjected to survival analysis with genomic and clinical data of 420 DLBCL patients from The Cancer Genome Atlas (TCGA) using a log-rank test. Area under the ROC curve (AUC) was derived to validate the predictive ability of the survival model. Results: Among all genes involved in SS-associated NHLs, 16 genes were significantly differentially expressed in all types of NHLs. These genes included CXCL13, SEPP1, COL1A1, RGS13, IGFBP7, COL3A1, SPARCL1, GABBR1, SLC40A1, CXCL14, CXCL12, CXCL9, CCL19, VCAM1, C3, and CLU. The fold changes of the 16 genes for DLBCL were 465.67, 209.68, 436.94, 366.94, 189.59, 456.09, 195.37, 152.05, 90.29, 26.29, 215.18, 72.06, 51.09, 91.91, 74.70, and 20.88, respectively. Among all SS-associated pathways underlying NHL pathogenesis, the endocannabinoid system-driven cancer inhibition pathways were most significantly altered in SS-associated NHLs. The z-scores of the cancer inhibition pathway were -0.14 for BL (-log10(P) = 4.54), -1.298 for DLBCL (-log10(P) = 3.00), -0.33 for FL (-log10(P) = 4.67), -0.87 for MCL (-log10(P) = 3.77), and -2.61 for MZL (-log10(P) = 4.31). Survival analysis revealed that together the 16 genes may serve as a prognostic biomarker of DLBCL (hazard ratio = 3.57, 95% CI = 2.53–5.03), which was statistically significant (log rank test P < 0.0001) and reliable (AUC = 0.897). Conclusions: Significant differentially expressed genes underlying the pathogenesis for SS-associated NHLs may be used as a biomarker for predicting the survival rate of DLBCL. Further studies are warranted to elucidate the functional association between these differentially expressed genes.
Adult malignancy-associated hemophagocytic lymphohistiocytosis: Case series.
Authors: Leão Inês , Couto Maria Eduarda , Marinho Joana Catarina Lima , Oliveira Isabel , Martins Ângelo , Mariz Mário 
Published: June 2021

e19579 Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening hyperinflammatory syndrome, with a challenging diagnosis (pediatric HLH-2004 criteria) and treatment (HLH-1994 protocol). Recently, HScore has adapted these diagnostic criteria to the adult population. Malignancy-associated HLH (M-HLH) can occur as the first manifestation of an unknown malignancy or after / during the treatment of a known cancer. This study evaluates features and outcomes of M-HLH in adult patients. Methods: Retrospective cohort study of all patients diagnosed with M-HLH in a single institution during 2013-2020. HLH-2004 and HScore criteria were used for diagnosis. Patients’ demographics, clinical and laboratory features, treatment and mortality were reviewed. Results: Eleven patients were analyzed. Ten fulfilled 5 of the HLH-2004 diagnostic criteria and one other had a HScore > 190 (80% probability of M-HLH). Median age was 68 years (IQR 62-71), and 54.5% were females. The median time between hospital admission and M-HLH diagnosis was 9 days (IQR 7-16). The most common malignancy was diffuse large B-cell lymphoma (36.4%), followed by Hodgkin lymphoma (18.2%), multiple myeloma (18.2%), myelodysplastic syndrome, T-cell and follicular lymphoma (9.1% each). Malignancy and HLH diagnosis were simultaneous in 54.5% of the cases (4 newly diagnose, 2 disease-progression); the remaining 5 patients were in remission (median time from cancer diagnosis to HLH of 9.9 months (IQR 5.1–38.3)). One patient also had an autoimmune disorder. An infectious co-trigger was identified in 81.8% of patients (virus in 45.5%, fungous in 36.4%, bacteria in 27.3%). The triad of fever, splenomegaly and cytopenia was present in 36.4% of patients. All had increased sCD25 and ferritin, with a median concentration of 7612U/mL (IQR 2631–34161) and 13269µg/L (IQR 6381–17911), respectively. The ratio between sCD25 and ferritin was 1.09 (IQR 0.13–3.05). Morphological M-HLH was documented in 8 out of the 9 biopsied cases. The HLH-1994 protocol was prescribed in 54.5% of patients (including intrathecal methotrexate in 2 patients), steroids as monotherapy were used in 18.2% and malignancy-specific chemotherapy in 36.4%. All but one patient initiated broad spectrum antibiotics at hospital admission, with an antifungal in 45.5% and an antiviral (valganciclovir) in 27.3%. At the time of analysis 63.6% of patients had died (overall, 54.5% within 3 months since M-HLH diagnosis). Conclusions: Most symptoms of M-HLH are common and unspecific, demanding a clinical suspicion and an early evaluation of ferritin, sCD25, triglycerides and fibrinogen. Co-triggers are frequent and their treatment is advisable. The disease has an unfavorable prognosis in a short period of time. This rare case series increases awareness about M-HLH (urgent need of updated diagnostic criteria and more efficient adult-adapted treatment strategies).
Clinical presentation of multiple myeloma by race/ethnicity and Asian subgroup in an integrated healthcare system.
Authors: Khan Adnan Ahmed , Fatoki Raleigh Ayoolu , Carpenter Diane M. , Lo Joan C. , Baer David M. 
Published: June 2021

e20012 Background: Several US studies have evaluated ethnic differences in patients with multiple myeloma (MM), but few have focused on populations other than non-Hispanic Whites and Blacks. We examined ethnic differences in a contemporary cohort of MM patients and their presenting laboratory findings in a large, insured, community-based population, including findings across Asian American subgroups. Methods: Using the Kaiser Permanente Northern California (KPNC) Cancer Registry, we identified all new cases of MM from 2010-2018 and obtained data on age, sex, race/ethnicity, Asian subgroup, and presenting hemoglobin, calcium, and estimated renal function (eGFR derived from serum creatinine) from health plan databases. Moderate to severe anemia was defined by hemoglobin <10 g/dL, hypercalcemia by calcium >11 mg/dL, and chronic kidney disease (CKD) by eGFR: stage 3 (eGFR 30-59) and stages 4-5 (eGFR <30). MM incidence was estimated using membership denominators. Results: There were 2224 new MM cases (mean age 68y, 60% male) in 2010-2018, with an annual MM incidence of 7.9-9.8/100,000. Table 1 compares presentation by race/ethnicity. Non-Whites (45%) were more likely to present at age <65 than non-Hispanic Whites (30%, p<0.01). Black (43%) and Asian (39%) adults were more likely to present with hemoglobin <10 g/dL than non-Hispanic Whites (27%, p<0.01); Black adults were more likely to present with hemoglobin <10 g/dL than Hispanic adults (31%, p=0.02). Among the primary Asian subgroups, proportions with hemoglobin <10 g/dL were 38% (East Asian), 43% (Filipino), and 45% (South Asian). Blacks were more likely to present with CKD stage 4-5 (19.5%) than other races/ethnicities (p=0.04); differences between White vs non-White or Asian vs non-Asian were not significant. In Asians, 12.7% (South Asian) and 19.0% (Filipino, East Asian) presented with CKD 4-5. Asians were least likely to present with hypercalcemia (6.7%, p=0.03), and this was similar for Asian subgroups. Conclusions: We observed ethnic differences in MM presentation in a large integrated healthcare system. Blacks were more likely to have CKD stage 4-5 and hemoglobin <10 g/dL than non-Hispanic Whites. Asians were more likely to have CKD stage 4-5 than non-Hispanic Whites but least likely to have hypercalcemia. This is one of the first studies to identify Asian subgroups and examine variation across East Asians, Filipinos, and South Asians. Analyses examining ethnic differences in survival among MM patients are in progress.[Table: see text]