bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying unmeasured confounding in three epidemiological studies associating myelodysplastic syndromes (MDS) with cardiovascular disease (CVD).
Authors: Singh Abhay 
Published: May 2020

e19532 Background: Confounding occurs when an investigator studies the effect of an exposure on the occurrence of an outcome, but in the process measures the effect of another factor (a confounding variable). Knowledge of possible causal pathways assists an investigator to minimize confounding, but despite utmost attempts, errors are frequent. To assess role of a possible confounder (smoking), data from 3 studies (1. Herrera at al. 2019 2. Goldberg et al. 2010 and 3. Brunner et al. 2017) associating MDS (exposure) with CVD (outcome) was used to conduct sensitivity analysis. Methods: 2 x 2 tables were constructed with data from 3 studies (part 2 of table below). A vector defining the proportion of confounder (smoking) among exposed [prop (Smoking+|MDS+)], unexposed [prop (Smoking+|MDS-)] and risk ratio associating smoking status with CVD (part 1) using historical data was deduced. Extracted data was added to online bias analysis tool ( https://sites.google.com/site/biasanalysis/ ) to calculate crude as well as mantel-haenszel (MH) relative risk (RR) adjusted for smoking. Results: RRs unadjusted for smoking status for studies 1, 2 and 3 were 1.31, 1.34 and 2.21, respectively, signifying increased risk of CVD in MDS patients (part 3). Upon adjustment for smoking status, MH-RR for MDS-CVD relationship was 0.95, 0.97 for studies 1 and 2 respectively, signifying no increased CVD risk and 1.59 for study 3 signifying increased CVD risk but lower upon adjustment. Conclusions: Making inference of MDS-CVD association without accounting for smoking status can blur effects and at times result in false associations. Given ambiguity in results from these 3 studies, further evidence is needed to better assess MDS-CVD relationship. A simple online tool allows estimating nonrandom errors, assess magnitude and direction of biases, and help clinicians/researchers quantify these biases for better interpretation of observational data in a time efficient manner. Other bias analyses for these studies will be presented. [Table: see text]
A real-world single-center retrospective study on efficacy and safety of pegylated interferon alpha-2a in patients with myeloproliferative neoplasm.
Authors: Ozcan Muhit , Koyun Derya , Cengiz Seval Guldane , Uslu Atilla , Kırcalı Ekin , Ozturk Cemaleddin , Civriz Bozdag Sinem , Toprak Selami Kocak , Topcuoglu Pervin , Arslan Onder , Ilhan Osman , Beksac Meral 
Published: May 2020

e19536 Background: Pegylated forms of interferon (PEG-IFN) have a better pharmacologic profile than short-acting interferons, resulting in a more convenient less-frequent schedule of injections, less immunogenicity and possibly less toxicity. Several clinical studies of PEG-IFN-α-2a have reported promising results in patients with essential thrombocythemia (ET) and polycythemia vera (PV). Herein, we present the outcomes of MPN patients treated with PEG-IFN-α-2a seen outside of a clinical trial setting at a single center. Methods: Thirty-five MPN Patients treated with PEG-IFN-α-2a between January 2014 and October 2019 were included this retrospective analyses. Therapeutic responses for ET and PV were calculated by the revised ELN/IWG-MRT criteria. Responses in myelofibrosis (MF) were calculated by both EUMNET and ELN/IWG-MRT criteria. Best responses over all cycles of treatment were assessed. Molecular data was limited to JAK V617F. Results: Twenty patients with ET, 13 with PV and two with MF were enrolled in this study. The median age at diagnosis was 47 years (range; 21-83 years). JAK2 V617F mutation was detected in 16 patients (45.7%). Overall, the majority of patients (62.9%) had received at least one prior cytoreductive therapy for underlying disease. Median starting dose of PEG-IFN-α-2a was 90 mcg/week via self injection (range: 45-135 mcg/w). Treatment duration was pursued for a median duration of 21.4 months (range: 1.2-109.8). In the PV/ET group 33 patients were evaluated and overall best response rate was 87.8% (CR in 15 pts and PR in 14 pts). In the MF group (n = 2); a PR was seen in one patient and CR in one patient. No vascular events occurred within the cohort while on therapy. Of the eight patients receiving at least phelebotomy per month, all patients became phelobotomy independent with therapy. Of the 20 ET patients, 12 patients (60%) had platelet normalization (< 450 x 109/L). Among all patients, fatigue (31.4%), muscle pain (20%) and depression (8.6%) were the most common adverse events (AEs). Any grade of hematological AEs was not seen with PEG-IFN-α-2a. Eleven patients discontinued therapy secondary to: treatment associated severe AEs in 8 patients, lack of response in two patients and pregnancy in one patient. No death was reported during the analyses period. Conclusions: Our results suggest that PEG-IFN-α-2a remains a viable treatment option especially for younger patients who want to avoid prolonged cytotoxic therapy.
Correlative study of disease activity in Langerhans cell histiocytosis.
Authors: Edwards Jeffrey Garnet , Jeng Michael Raymond 
Published: May 2020

e19540 Background: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia that primarily affects younger children, most often involving bone, skin, lung, lymph nodes, or liver. Current treatment for LCH includes chemotherapy and biologically targeted therapies. Given its clinical heterogeneity and low prevalence, decision-making regarding intervention relies on subjective evaluation of disease status, which is often dependent on provider experience. Thus, there is a need to identify biomarkers for disease recurrence and activity in patients with LCH. Methods: We conducted a retrospective cohort study including pediatric LCH patients (n = 48) ≤21 years of age with biopsy-proven diagnosis of LCH and ≥1 year of follow-up after diagnosis. Data regarding demographics, symptom history, organ system involvement, and laboratory values at different time points were extracted from the from patient medical records and entered into a REDCap Database. The primary outcome was recurrence status as measured by the end of the study period. Data were analyzed using Stata statistical analysis software. Results: In our cohort, the sample was 64.6% Male and 35.4% Female with a median age of 29 months at diagnosis. 68.1% of patients had single organ involvement while 31.9% exhibited multi-system involvement. 70.8% of our cohort received treatment with chemotherapy with an average initial treatment duration of 12.1 months. 27.1% of the cohort experienced recurrence by the time of chart review. Logistic regression of the demographic factors and lab values at diagnosis revealed a statistically significant association between multi-system involvement (OR: 3.94, p = 0.04), moderate or high central nervous system risk assessment (OR: 7.67, p = 0.03; OR: 5.75, p = 0.03) and likelihood of recurrence. Additionally, logistic regression analysis revealed that alkaline phosphatase level at the time of diagnosis was associated with a slightly decreased likelihood of recurrence (OR: 0.987, p = 0.02). Conclusions: These results reveal that in addition to the traditionally utilized inflammatory markers (Erythrocyte Sedimentation Rate, White Blood Cell and Platelet Count), Alkaline Phosphatase could be used as a predictor of disease activity for patients with LCH, especially for those with bone involvement. Moving forward, an increased sample size might reveal other correlative biomarkers that can predict disease activity, helping to more precisely manage LCH.
Leveraging real world data and AIML to inform smart patient care in oncology.
Authors: Zhou Li , Steen Rob , Lu Lynn 
Published: May 2020

e20002 Background: Identifying optimal therapy options can help maximize treatment outcomes. Finding ways to help improve treatment decision is of great value to achieve better patient care. With the availability of robust patient real world data and the application of state of the art Artificial Intelligence and Machine Learning (AIML) technology, new opportunities have emerged for a broad spectrum of research needs from oncology R&D to commercialization. To illustrate the above advancements, this study identified patients diagnosed with CLL who may progress to next line of treatment in the near future (e.g. future 3 months). More importantly, we can identify treatment patterns which are more effective in treating different types of CLL patients. Methods: This study includes multiple steps which have already been analyzed for feasibility: 1. Collect CLL patients. IQVIA's real world data contains ~60,000 active CLL treated patients. ~2,000 patients have progressed line of treatment in 3 month. 2. Define patients into positive and negative cohorts based on those who have/have not advanced to line L2+. 3. Determine patient profiles based on treatment regimens, symptoms, lab tests, doctor visits, hospital visits, and co-morbidity, etc. 4. Select patient and treatment features to fit an AIML predictive model. 5. Test different algorithms to achieve best model results and validate model performance. 6. Score and classify CLL patients into high and low probability based on the predictive model. 7. Match patients based on feature importance and compare regimens between positive and negative cohort. Results: Model accuracy is above 90%. Top clinical features are calculated for each patient. Optimum treatment patterns between high and low probability patients are identified, with controlling patient key features. Conclusions: Conclusions from this study is expected to yield deeper insight into more tailored treatments by patient type. CLL patients started with oral therapy(targeting) have better response than other treatments.
Toxicity burden in older patients with chronic lymphocytic leukemia (CLL) receiving bendamustine with rituximab (BR) or ibrutinib (IB) regimens: Alliance A041202.
Authors: Ruppert Amy S. , Mandrekar Sumithra J. , Booth Allison M. , Ding Wei , Bartlett Nancy L. , Brander Danielle M. , Coutre Steve E. , Brown Jennifer R. , Nattam Sreenivasa R. , Larson Richard A. , Erba Harry Paul , Litzow Mark Robert , Owen Carolyn , Kuzma Charles S. , Abramson Jeremy S. , Little Richard F. , Smith Scott E. , Stone Richard M. , Byrd John C. , Woyach Jennifer Ann 
Published: May 2020

e20004 Background: IB is a Bruton’s tyrosine kinase inhibitor that showed superior progression-free survival compared with BR in CLL patients (pts) 65 years or older in a randomized phase 3 trial (Woyach et al, NEJM 2018). Pts receiving IB had higher rates of atrial fibrillation (AFIB) and hypertension (HTN); BR pts had higher rates of hematologic toxicity. Differences in treatment duration for BR (6 cycles) and IB (until progression) complicated adverse event (AE) comparisons. Here we use an exploratory approach to compare toxicity burden between arms and provide assessment of AFIB, HTN and infections (INF). Methods: AEs were reported for each of cycles 1-6 and then every 3 cycles until progression or nonprotocol CLL therapy. Only grade (gr) 3-4 AEs were reported thereafter until death. A simple global AE score was calculated for each pt by summing grades of all gr 1-4 AEs and dividing by the number of cycles over which AEs were submitted. Results: 537 pts began therapy (176 BR, 361 IB). 68% on BR completed all 6 cycles. At a median follow-up of 38 months, 64% remained on IB. Treatment discontinuation for AE occurred in 10% and 14% of BR and IB pts. Overall, median AE score was 1.8 (interquartile range (IQR) 0.9-3.3) and 3.8 (IQR 2.3-5.9) in BR and IB arms (p < 0.01). For cycles 1-6, median AE score was 6.2 (IQR 3.8-9.0) and 4.8 (IQR 3.0-7.2) in BR and IB arms (p < 0.01). In the IB arm, median AE score post 6 cycles decreased significantly to 3.4 (IQR 1.9-5.6) (p < 0.01). Gr 3 or higher cumulative rates of AFIB, HTN, and INF over time appear in the table. 100 pts (26/176 BR, 74/361 IB) had 137 severe INF (39% respiratory: 16 BR, 37 IB; 25% skin: 3 BR, 31 IB; 12% GU: 3 BR, 13 IB; 25% other: 12 BR, 22 IB). There were 7 gr 5 INF (3 BR, 4 IB), none confirmed fungal. Conclusions: There was no difference in treatment discontinuation rates for AE. Overall toxicity burden was significantly higher for IB, although IB toxicity burden decreased after 6 cycles. Toxicity burden was significantly higher in cycles 1-6 for pts receiving BR. Risk of severe AFIB, HTN, and INF is highest in the first year of IB. A simple AE score provides valuable information, especially when evaluating regimens of varying length. Clinical trial information: NCT01886872 . Support: U10CA180821, U10CA180882, U24CA196171; https://acknowledgments.alliancefound.org ; Pharmacyclics; ClinicalTrials.gov Identifier: NCT01886872. [Table: see text]
The association between tonsillectomy and Hodgkin’s lymphoma: A systematic review and meta-analysis.
Authors: Albawaliz Anas , Fatima Zainab , Abonofal Abdulrahman , Abumoawad Abdelrhman , Al Momani Laith , Shrestha Anuj 
Published: May 2020

e20015 Background: Several observational studies have evaluated tonsillectomy as a predisposing factor for developing Hodgkin’s lymphoma (HL) with contradicting results. The true association is unknown. We sought to systematically review the literature and perform the first meta-analysis to study the association between a history of tonsillectomy and the development of HL. Methods: A systematic review was conducted in Pubmed, and Cochrane databases from inception through January 2020 to identify the studies which explored the association between history of tonsillectomy and HL. Effect estimates from the individual studies were extracted and combined using the random effect, generic inverse variance method of DerSimonian and Laird and a pooled odds ratio (OR) was calculated. A forest plot was generated, and publication bias was assessed for using conventional techniques. Results: Twenty studies with a total of 17931 patients were included in our analysis. 6231 of the patients were diagnosed with HL. The pooled OR for the development of HL in patients with history of tonsillectomy was 1.237 (CI 1.075-1.424, P = 0.003, I2= 45.073%) compared to patients without a history of tonsillectomy. Conclusions: Our analysis shows a statistically significant association between a history of tonsillectomy and the development of HL. As all the studies included in our meta-analysis were observational, we need prospective studies to better understand this important association.
Causes of death in nodular lymphocyte predominant Hodgkin's lymphoma.
Authors: Saad Anas M , Afifi Ahmed , Gad Mohamed , Al-Husseini Muneer J. , Baidoun Firas , Hilal Talal 
Published: May 2020

e20016 Background: Nodular lymphocyte-predominant Hodgkin’s lymphoma (NLPHL) accounts for 5% of all cases of HL. The outcomes of patients with NLPHL is generally regarded as better than those with classical HL. However, causes of death (COD) of patients with NLPHL have not been previously described. Methods: The National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program was used to identify all patients with NLPHL diagnosed between 1990 and 2015. Patient characteristics and disease stage, using the Ann-Arbor system, was extracted and tabulated. COD were identified and proportions were calculated for deaths within 5 years and after 5 years of diagnosis for patients with early and late stage NLPHL. Results: We identified 1,937 cases of NLPHL. The majority were younger than 65 years (86%), white (70%), male (67%), and diagnosed between 2001-2015 (85%), when rituximab was introduced. Of all cases, 1336 (69%) were classified as early stage. At a median follow-up of 91 months (IQR 41, 152) for early stage disease, and 73 months (IQR 30-123) for late stage disease, the median cancer-specific or overall survival were not reached. The estimated 5-year survival was 92% and 81% for early stage and late stage disease, respectively. Of all patients with early stage NLPHL, 186 (14%) died by the end of 2015, and 87 (46%) deaths occurred within 5 years of diagnosis. During the first 5 years after diagnosis, COD was NLPHL in 30 (35%). Beyond 5 years from diagnosis, NLPHL was the COD in 27% followed by other cancers (23%), and cardiovascular disease (18%). Of all patients with late stage NLPHL, 107 (21%) died, and 75 (70%) of deaths occurred within 5 years of diagnosis. During the first 5 years after diagnosis, COD was NLPHL in 44 (59%). Beyond 5 years from diagnosis, cardiovascular disease was the COD in 25%, followed by NLPHL (22%). Conclusions: The prognosis of NLPHL is excellent. Of all patients with NLPHL, those with advanced stage disease are more likely to die of their disease within 5 years of diagnosis. Patients with early and advanced stage disease beyond 5 years of diagnosis are more likely to die of causes other than NLPHL.
The Hodgkin lymphoma international study for individual care (HoLISTIC): Enhancing decision making in pediatric and adult Hodgkin lymphoma (HL).
Authors: Parsons Susan K. , Rodday Angie Mae , Scharman Carlton , André Marc , Federico Massimo , Friedberg Jonathan W. , Friedman Debra L. , Gallamini Andrea , Hay Annette E. , Hoskin Peter , Johnson Peter , Kahl Brad S. , Keller Frank G. , Kelly Kara M. , Meyer Ralph M. , Radford John A. , Raemaekers John , Zinzani Pier Luigi , Cohen Joshua T. , Evens Andrew M. ,   on behalf of the HoLISTIC Consortium
Published: May 2020

e20019 Background: Decision making in HL is complicated by clinical trial results that differ, a growing range of treatment options, and the absence of ideal, objective information on long term outcomes from modern therapy. Methods: We formed an international consortium, HoLISTIC, consisting of 50+ pediatric & adult HL providers, decision scientists, statisticians, epidemiologists, and patient (pt) advocates and are creating a data repository of individual pt data (IPD) from 16 contemporary, pediatric & adult clinical trials for newly diagnosed pts with HL, and 6 large HL registries/survivorship cohorts, the latter enriched with LE data (Table). We will enhance our prior decision model (DM) from group-level data (Parsons S et al. B J Haem 2018) to establish a dynamic HL DM from IPD. Using statistical and simulation modeling of IPD, the enhanced DM will project outcomes of interest, including quality-adjusted life years (QALYs), reflecting both mortality and morbidity. Results will be validated and calibrated against prominent external cohorts (e.g., St. Jude LIFE Cohort, Dutch HL registry). The DM then will be converted to a web-based platform that we will test and evaluate among HL providers and pts at the point of care. Results: To date, we have harmonized IPD from 10 trials (~8,000 HL pts), ranging in size from 165-1925 pts. At diagnosis, median age was 26 y (IQR 18-38); 51.5% were male. 43% had B symptoms, 34% had mediastinal bulk, and 79% had nodular sclerosis histology. Median follow up was 5.0 y (IQR 3.5-7.4). IPD harmonization is ongoing, which will be followed by creation of the enhanced DM. Conclusions: HoLISTIC capitalizes on a multidisciplinary pediatric & adult oncology collaborative, harmonizing extensive IPD by linking data from clinical trials and real world registries/survivorship cohorts. This work will inform questions about the influence of Tx options on both acute and potential long term events and how those options align with pt values and preferences. [Table: see text]
Brentuximab vedotin with chemotherapy for advanced stage untreated classic Hodgkin’s lymphoma in a real-world setting.
Authors: Steiner Raphael , Cramer Frederick M , Singh Prachee , Becnel Melody , Alcedo Pedro E , Chin Collin K , Cuglievan Branko , Strati Paolo , Ahmed Sairah , Samaniego Felipe , Nair Ranjit , Gunther Jillian Rebecca , Pinnix Chelsea Camille , Fang Penny , Dabaja Bouthaina Shbib , Feng Lei , Lee Hun Ju 
Published: May 2020

e20020 Background: In the pivotal phase III study ECHELON-1, Brentuximab Vedotin (BV), doxorubicin, vinblastine, and dacarbazine (A+AVD) demonstrated superior efficacy but more hematological and neurological toxicity than bleomycin+AVD (ABVD) as therapy of advanced-stage untreated classic Hodgkin’s lymphoma (ucHL) (Straus et al Blood 2020). It is unknown if A+AVD in a real world setting shows the same efficacy and safety profile. Methods: After obtaining institutional research approval, we retrospectively reviewed the characteristics and outcomes of 41 stage III and IV ucHL patients treated per physician preference with A+AVD as standard of care between 3/2010 and 12/2019. Treatment consisted of 1.2 mg/kg of BV and standard dose AVD, intravenously on days 1 and 15 of each 28-day cycle for up to 6 cycles. All patients received support with granulocyte colony stimulating factor. Results: At time of treatment with A+AVD, median age was 38 (range 18-54 years) and IPS was 0-3 in 56% of patients. Overall, 95.1% of patients received 6 cycles of A+AVD, with a range of 3-6 cycles. During therapy, 19.5% of patients developed febrile neutropenia, 68.3% had at least one emergency department visit (median 2 visits, range 1-7), and 58.5% were hospitalized at least once (median hospital stay of 3 days, range 1-23). Furthermore, 4.9% of patients presented with grade ≥3 elevation of lipase, 4.9% grade ≥3 elevation of alanine aminotransferase, 9.8% deep vein thrombosis and 7.3% pulmonary embolism. Peripheral neuropathy (PN) occurred in 78% of patients, including grade ≥3 in 12.2%. Due to various toxicities, 22% of patients required at least one dose reduction of BV (median 5 reductions, range 2-7) and 46.3% had a least one dose omission of BV (median 4 omissions, range 1-10). At a median follow-up (FU) of 12.65 months (range: 5.91-85.97), 87.5% of patients had partial or complete improvement of their PN. The median delay of completion of 6 cycles of A+AVD was 8 days (range -1 to 35). The end-of-therapy PET/CT showed Deauville score of 1-3 in 85.3% of patients, 4 in 2.4% and 5 in 12.2%. However, only one patient relapsed 5 months after completion of 4 cycles of A+AVD and another relapsed 6 months after completion of 6 cycles. Both patients were still alive at last FU. The median PFS was not reached and 12-months PFS was 96.0% (95% confidence interval [CI], 88.6-100). Conclusions: In real-world experience, A+AVD is a highly effective treatment strategy for patients with advanced-stage ucHL. In light of its toxicity profile, strategies aimed at improving its safety are needed.