bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shifting revenue from drug sales to cognitive services: Impact on physician prescribing behavior.
Authors: Feinberg Bruce A. , Cooper Joseph , Wong Winston , Winn Daniel , Olson Tim , Trehan Ram Swarup , Scott Jeffrey A. 
Published: March 2020

6629 Background: Extensive literature has cited fee-for-service physician reimbursement methodology as a critical driver of resource utilization constituting overtesting, overtreatment, and an impediment to bending the cost curve in cancer care. CareFirst BlueCross BlueShield (CFBCBS) partnered with Cardinal Health Specialty Solutions to launch the first cancer clinical pathway in the US in Aug 2008. Physician participation was voluntary and reimbursement remained fee-for-service. Due to its early success with regard to savings and physician participation and compliance, an oncology medical home (MH) program was piloted in Jan 2011 offering a new physician reimbursement model, which shifted the source of revenue from margin on drug sales to cognitive services. This would allow physicians to focus on optimal patient (pt) care without the financial incentive to prescribe chemotherapy (chemo). We analyzed physician behavior modification after this change in reimbursement structure 1 year after implementation of the MH program. Methods: Practices that participated in the first pathways program were eligible to join the MH program. Claims data from CFBCBS were collected from Apr 2010 to Mar 2012. New and established pt visits, chemo administrations (admins) per pt and per practice, and % generic drug use were compared for year +1 versus year -1 of the MH program. Results: Fourteen practices (31 physicians, 478 pts) joined the MH program. In year +1, new pt visits increased by 2.7%, visits per established pt increased 1%, chemo admins per pt increased by 3%, and the percentage of regimens utilizing all generic drugs increased by 3.9%. Conclusions: Switching financial incentives from drug administration toward cognitive services did not significantly alter physician behavior with regard to the type or frequency of chemo admins or the frequency of pt visits. Whether this is because the physicians were mature pathways participants, influenced by brand-name prescription drug detailing, following National Comprehensive Cancer Network guidelines, or influenced by cognitive dissonance is speculative. Assumptions regarding fee-for-service reimbursement may not be applicable to chemo and will be further studied.
Predictors of significant emotional distress in cervical cancer patients.
Authors: Osann Kathryn , Hsieh Susie , Nelson Edward L. , Cella David , Wenzel Lari B. 
Published: March 2020

6632 Background: Cervical cancer patients experience serious quality of life (QOL) disruptions, which may include persistent emotional distress. Predictors of persistent or significant depression and anxiety are examined in this study. Methods: A randomized trial tested the efficacy of a psychosocial telephone counseling intervention designed to improve QOL and decrease emotional distress.The FACT-Cx Trial Outcome Index (FACT-Cx-TOI), depression and anxiety (PROMIS short forms) were collected at baseline (T1), 4 months (T2) and 9 months (T3) post enrollment. Multivariate linear and logistic regression models were used to identify predictors of distress at follow-up. Tested predictors included demographic information, stage, treatment assignment, and baseline FACT-Cx TOI and PROMIS scores. Results: 115 women were randomized to PTC and 89 to usual care, with 82% compliance for T2 and 75% at T3. PTC patients experienced a significantly greater reduction in depression from T1 to T2 compared to UC (p=0.014). At baseline, 45% of participants reported depression T-scores above 55 (0.5 SD above the US general population average), and 26% reported levels greater than 60 (>1 SD worse than average). PTC patients were significantly less likely to have depression scores >55 at T2, and significantly more likely to improve by ≥5 points at T2 after adjusting for baseline and disease characteristics. Participation in PTC, higher baseline depression and higher baseline TOI were significant independent predictors of improvement in depression from T1 to T2. Conclusions: Early identification of patients with poor QOL and significant depression can inform supportive care interventions, with potential to improve health outcomes. Funding Source: NCI R01 CA118136-01. Clinical trial information: NCT00496106.
Rothman index as a predictor for type of discharge and readmission rates in a cancer hospital: The Yale experience.
Authors: Morgensztern Daniel , Xia Bing , Kournioti Chryssanthi S. , Hofstatter Erin Wysong , Raucci Maureen , Keyes Ashley , Morrione Alienne , Blasiak Elizabeth , Rosenberg Elizabeth , Rimar Joan , Rothman Michael J , Lilenbaum Rogerio 
Published: March 2020

6635 Background: There is limited data on predictors of discharge (DC) and readmission (RA) for oncology inpatients. The Rothman index (RI) is a single score calculated from 26 parameters including nursing assessments, vital signs, and laboratory tests, integrated with the hospital’s electronic medical record and automatically updated when new data are entered. Scores are inversely related to patient impairment. We evaluated the role of RI in the prediction of DC types and RA rates at the Smilow Cancer Hospital at Yale. Methods: Patients (pts) with solid tumors, length of stay longer than 24 hours, admitted between 6/1/11 and 12/31/11 were enrolled. Elective admissions were excluded. DC types were classified as home without hospice (Hm), nursing home (NH), hospice (Hp) and death (D). The RI at the time of DC was evaluated as a predictor for RA at 7 or 30 days and the type of DC. Analysis of variance (ANOVA) was used to determine whether there were statistically significant differences between RI means and DC categories, followed by pair-wise contrast using the Tukey method. Results: Among the 476 admissions from 331 pts, the median age was 63 (range 21-92, 23% age 70 or older), and 55% males. The most common tumors were lung (24%) and breast (8%). The number of DCs were 313 Hm (66%), 75 NH (16%), 55 Hp (11%) and 33 D (7%). RI at DC for H, NH, Hp and D were 74, 62, 47 and 23. All comparisons among RI at DC and type of DC were significant (p < 0.05). Among the Hm pts, the rates of RA at 7 days were significantly higher for RI < 50 (45%) and 50-60 (32%) compared to 81-90 (13%) and > 90 (7%) (Table). RA rates at 30 days were also related to RI at DC, ranging from 65% in RI < 50 to 33% in RI > 90. Conclusions: RI is a useful tool in the evaluation of inpatients by providing an objective metric at the time of DC. The high correlation between RI scores and both DC type and RA rate underscores the need for a more consistent and reproducible evaluation at the time of DC and may be used by health care providers to guide disposition planning. A prospective study is being planned at our institution. [Table: see text]
Incidence of posttransplantation lymphoproliferative disorder (PTLD) following allogeneic blood or marrow transplantation (alloBMT) using post-transplantation cyclophosphamide (PT-Cy) for graft-versus-host disease (GVHD) prophylaxis.
Authors: Kanakry Jennifer Ann , Kasamon Yvette L. , Swinnen Lode J. , Bolanos-Meade Javier , Gladstone Douglas , Symons Heather J. , Mogri Huzefa J. , Kanakry Christopher George , Gocke Christopher D , Luznik Leo , Fuchs Ephraim Joseph , Jones Richard J. , Ambinder Richard F. 
Published: March 2020

7009 Background: Immunosuppression to prevent graft rejection and GVHD is associated with an increased incidence of PTLD in the first year after alloBMT. AlloBMTs using partially HLA-mismatched or unrelated donor grafts, particularly when coupled with selective T-cell depletion approaches and/or anti-thymocyte globulin therapy, are associated with PTLD rates of 4-8%. The incidence of PTLD after umbilical cord blood alloBMT ranges from 2-7%. We evaluated the incidence of PTLD associated with the use of PT-Cy as GVHD prophylaxis at Johns Hopkins Hospital. Methods: After IRB approval, the Blood and Marrow Transplant Research database was queried for adult patients (age > 18) who received PT-Cy as GVHD prophylaxis. Medical records from the first year after alloBMT, including clinical notes, pathology reports, and laboratory assays for Epstein-Barr virus (EBV), were reviewed. Results: From 2000-2011, 765 alloBMT patients received PT-Cy (50 mg/kg/day on days 3 and 4 after alloBMT) as GVHD prophylaxis. Of these, 734 patients had 1-year follow-up or death. In patients receiving myeloablative conditioning and HLA-matched grafts (n=289, 117 unrelated donors), PT-Cy was the sole GVHD prophylaxis. Other patients undergoing alloBMT received mycophenolate mofetil and tacrolimus in addition to PT-Cy. These included recipients of HLA-matched (n=63) or haploidentical (n=352) grafts who were conditioned with reduced intensity regimens, as well as recipients of HLA-haploidentical grafts who received myeloablative regimens (n=30). Forty-one patients with CD20(+) tumors received rituximab after alloBMT as part of a clinical protocol. There were no cases of PTLD. Conclusions: The absence of PTLD in this series, even among high-risk recipients of haploidentical or unrelated donor grafts, suggests that PT-Cy is less associated with PTLD than other GVHD prophylaxis strategies. We hypothesize that multiple mechanisms may account for the lack of PTLD with PT-Cy, including destruction of B cells that harbor EBV, sparing of EBV-specific memory T cells, and rapid immune reconstitution.
Impact of monosomal karyotype and FLT3 status on post-transplant relapse in acute myeloid leukemia (AML).
Authors: Jimenez Antonio Martin , De Lima Marcos , Popat Uday R. , Borthakur Gautam , Abruzzo Lynne , Andersson Borje , Garcia-Manero Guillermo , Jabbour Elias , Chen Julianne , Bashir Qaiser , Ciurea Stefan O. , Kebriaei Partow , Ahmed Sairah , Khouri Issa F. , Kongtim Piyanuch , Qazilbash Muzaffar H. , Rondon Gabriela , Shpall Elizabeth J. , Champlin Richard E. , Oran Betul 
Published: March 2020

7010 Background: Relapse remains the major cause of treatment failure in AML patients (pts) undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT). We aimed to identify prognostic factors for relapse and leukemia free survival (LFS) after allo-HCT in AML pts. Methods: We retrospectively analyzed 987 consecutive pts who underwent their first allo-HCT for AML between January 2001 and June 2012. 124 pts had monosomal karyotype (MK+), 440 had other cytogenetic abnormalities (core-binding factor [CBF] n=67; MK-, n=373). 113 pts had diploid cytogenetics and FLT3 mutations (CN-FLT3+), 235 were diploid without FLT3 mutations (CN-FLT3-); FLT3 data was unavailable for 75 CN pts. Pts were stratified based on disease status at HCT: complete remission (CR, n=627) and active disease (n=360). Results: In this cohort, median age was 52 years (range: 19 – 76) and 191 pts (20%) had secondary AML (sAML). Conditioning intensity was non-myeloablative in 230 pts (23%). On multivariate analysis in pts with CR at HCT (adjusted for age, donor type and conditioning intensity) factors that predicted inferior LFS included: sAML (HR=1.5, 95% CI=1.1-2.2, p=0.009), >=CR2 vs. CR1 (HR=1.6, 95% CI=1.2-2.1, p=0.002), CN-FLT3+ (HR=1.7, 95% CI=1.1-2.5, p=0.02), MK- (HR=1.4, 95% CI=1.1-2.0, p=0.04) and MK+ disease (HR=2.1, 95% CI=1.4-3.2, p <0.001). Three-year LFS rates for CN-FLT3+ and MK+ were 45.3% and 34% vs. 53.3% for CN-FLT3- pts. For pts with active disease; CN-FLT3+ (HR=2.6, 95% CI= 1.5-4.2, p<0.001) and MK+ (HR=2.3, 95% CI= 1.5-3.5, p<0.001) predicted worse 3-year LFS: 10% and 6% vs. 30.8% in pts with CN-FLT3- . For CR pts, cumulative incidence of relapse (CIR) was higher for those with CN–FLT3+ (HR=1.9, 95% CI=1.1-3.1, p=0.01) and MK+ disease (HR=2.1, 95% CI=1.2-3.5, p=0.005). Among active disease pts, CN-FLT3+ (HR=2.5, 95% CI=1.4-4.3, p=0.002) and MK+ (HR=1.9, 95% CI=1.2-3.0, p=0.009) also predicted for higher CIR. Conclusions: Although pts with CN-FLT3+ and MK+ represent a high risk group for decreased LFS with increased relapse incidence after allo-HCT, they may still enjoy LFS of 30% - 45% if transplanted in CR. Post-transplant strategies to minimize the risk of relapse should be investigated in this setting.
Comparison of allogeneic stem cell transplantations in chronic myeloid leukemia before and after the era of tyrosine kinase inhibitors.
Authors: Ozcan Muhit , Ozturk Bengi , Ozen Mehmet , Topcuoglu Pervin , Arat Mutlu , Arslan Onder , Ilhan Osman , Akan Hamdi , Beksac Meral , Konuk Nahide , Gurman Gunhan 
Published: March 2020

7038 Background: In this retrospective study we aimed to evaluate the rates and the clinical outcomes of allo-HSCT in CML following the advent of TKIs. Methods: We compared the transplantations (Txs) performed prior to 2002 (old era), the first year of TKIs, with the Txs during and after 2002 (new era). Results: Between 1989 and 2012 inour Tx unit a total of 189 allo-HSCTs were performed in 185 CML patients (second Tx for 4 patients). The ratio of Tx for CML among the whole Tx group decreased from 40 % to 12 % after 2002. The ratio also dropped to less than 5 % after 2008 and increased again to 15% in 2012. Time from diagnosis to Tx was longer in the old era than in the new era (9.2 months vs 15.4 months, p<.0001). The ratio of patients with advanced disease (accelerated or blastic phase) was higher in the new era. Although the progression free survival (PFS) was shorter in the new era than in the old era (median 13.8 months vs 37.1 months, p=0.09), overall survival, Tx outcomes and survival curves did not change. Conclusions: AlloHSCT rates sharply decreased after the TKIs, but a slight increase in recent years have been observed compatible with the TKI’s failure in years. Despite the fact that patients who underwent allo HSCT in the new era had more challenging disease biologically, overall survival was not affected possibly due to post-Tx interventions such as use of TKI alone or with donor lymphocyte infusion. [Table: see text]
Open label evaluation of ECG in patients with chronic lymphocytic leukemia (CLL) receiving ibrutinib monotherapy.
Authors: Loury David , Sukbuntherng Juthamas , Clow Fong , James Danelle Frances , Kunkel Lori A. 
Published: March 2020

7057 Background: Ibrutinib is a first-in-class selective small molecule inhibitor of Bruton’s tyrosine kinase (BTK) under development for the treatment of B-cell malignancies. The aim of this study was to characterize the possible effect of ibrutinib on ECG intervals in patients with CLL. Methods: A Phase Ib/II study (PCYC-1102-CA) of oral dosing of ibrutinib was conducted in patients with treatment-naïve (TN) or relapsed/refractory (R/R) CLL. Patients were enrolled into 6 groups treated with ibrutinib at 420 mg/day or 840 mg/day (n=132). One cycle was 28 days. ECG data were obtained along with the blood samples during Cycle 1. Additional ECG measurement was performed on Day 28 of Cycles 3, 6, 12, 18, and 24 and at the end of study. An interim ECG analysis was performed using the data from R/R patients at 420 mg/day (n=18), TN patients at 420 mg/day (n=20), and R/R patients at 840 mg/day (n=29). For ECG analysis, the pre-dose values on Cycle 1 Day 1 were used as the baseline for each post-dose time-point for all ECG parameters. The QT and RR values for each beat were used for both Fridericia's correction (QTcF) and Bazett's correction (QTcB). The relationship between plasma concentrations of ibrutinib and ΔQTcF (change-from-baseline QTcF) was investigated by a linear mixed-effects modeling approach. Results: Median ages for R/R 420 mg, TN 420 mg, and R/R 840 mg dose groups were 59, 71, and 62 years, respectively. There was no clinically significant change in heart rate (HR) relative to baseline observed in either dose groups or between R/R and TN populations. There was no evidence of PR interval prolongation above 240 msec. There were no treatment-related effects on QRS duration in any of the Treatment Groups. A total of 467 ΔQTcF measurements were included in the analysis. The population mean of baseline QTcF values was 402.0 msec with a SD of 15.2 msec. A concentration-dependent effect of ibrutinib on QTcF was not identified. Conclusions: Interim analyses of the data indicated that there was no evidence of clinically significant ECG findings or QTc prolongation with continuous daily dosing of ibrutinib at either the 420 mg or 840 mg dose in patients with TN or R/R CLL. Clinical trial information: NCT01105247.
Chemokine receptors as novel targets of the oncogene Notch1 in acute lymphoblastic leukemia.
Authors: Mirandola Leonardo , Chiriva-Internati Maurizio , Cobos Everardo , Yu Yuefei , Figueroa Jose A. , Garavelli Silvia , Colombo Michela , Lazzari Elisa , Platonova Natalia , Zepeda Kristopher , Jumper Cynthia A. , Jenkins Marjorie , Alalawi Raed , Konala Venu , Aulakh Amardeep , Radhi Saba , Chiaramonte Raffaella 
Published: March 2020

7060 Background: Malignant cells from different cancers express different profiles of chemokine receptors (CKR). Their presence may influence site-specific spread of tumor cells, by enabling them to respond to chemokine gradient, and may increase cell sensibility to chemokine mediated proliferative and anti-apoptotic stimuli. Notch ability to positively regulate CKR has been reported: stimulation of Pax5-/- pre-B cells with the Notch ligand Delta-1 results in induction of transcripts for CCR4, CCR8 and CXCR 6; the Delta-1-dependent regulation of Langerhans cell development includes induction of CCR6 expression resulting in the activation of chemotactic response to MIP-1a; Notch controls CCR7 signaling a regulator of CNS infiltration in T-acute lymphoblastic leukemia (T-ALL). Methods: This work aims to explore the correlation between the activation of the Notch oncogenic pathway in T-ALL and multiple myeloma (MM) cells and the aberrant expression CKR. Human T-ALL cell lines were treated with the Notch activation inhibitor, DAPT, or with a potent inhibitor of the Notch target, C-MYC, and evaluated the expression and functions of CCR9, CCR5, and CXCR4. Results: Treatment of human T-ALL and MM cell lines with pharmacologic inhibitors of Notch receptor activation produced a significant reduction of CCR9, CCR5 and CXCR4 expression, at both mRNA and protein levels. Results were confirmed by chemotaxis and survival assays. We identified the product of C-MYC gene as a possible mediator of Notch effect in regulating CKR networks in T-ALL and MM. Conclusions: These results suggest that Notch receptors play a previously unknown role in cancer progression and metastasis, by maintaining the expression levels of CKR. In conclusion, the identification of the potential axis Notch/CKR could have a prognostic value and provide the rationale for a tailored approach, since both Notch and CKR are targeted by emerging drugs.
Genetic and cytokine profiles associated with symptomatic stage of CLL.
Authors: Agarwal Amit Balkrishna , Cooke Laurence , Riley Christopher , Mount David , Mahadevan Daruka 
Published: March 2020

7062 Background: Pathogenesis of symptomatic CLL involves genetic changes associated with the CLL clone and changes within the microenvironment which contribute to chemo-resistance. To further understand these processes we compared early stage CLL to symptomatic late stage CLL using gene expression profiling as well as serum cytokine profiling for a better insight of the genetic and microenvironment changes associated with the most severe forms of the disease. Methods: We obtained pretreatment blood samples from CLL patients (10 low stage and 14 high stage) at the time of diagnosis. Patients were classified as low stage (Rai stage 0/I/II) and high stage (Rai stage III/IV). Gene expression profiles were obtained on a subset of patients using the HG-U133A 2.0 Affymetrix platform and analyzed for differential gene expression profiles. Serum from a subset of patients was used to perform cytokine profiling using the Raybiotech Cytokine Array platform (AAH-CYT-G1000) that allows for simultaneous measurement of >100 different cytokines. Results: Comparison of low versus high stage CLL revealed a set of 21 differentially expressed genes. 15 genes were up regulated in the high stage versus low stage, while 6 genes were down regulated. GO Molecular function analysis revealed that 9 of the 21 genes are involved in transcription factor activity. Other genes up regulated in the high stage group include CSNK1- shown to be involved in Myc derived oncogenesis and SETD8- a histone lysine methyltransferase previously implicated in several cancers. Serum cytokine profiles showed 6 cytokines to be significantly different in high stage patients. Two chemokines SDF-1/CXCL12 and uPAR known to be involved in stem cell mobilization and homing are increased in the serum of high stage patients. IGFBP-2, BMP-4 and MCP-4 were lower among high stage patients. Conclusions: Our study revealed a novel group of transcription factors are associated with higher stage CLL. Cytokine profiling showed increased levels of SDF-1/CXCL12, a chemokine that plays a key role in mobilization and homing of hematopoietic stem and CLL cells in high stage patients. Our study identifies putative therapeutic targets including CSNK1, SDF-1 and SETD8 for patients with high stage CLL.
Effect of obesity on overall survival in patients diagnosed with chronic myelomonocytic leukemia (CMML).
Authors: Alfakara Dima , Swedeh Amer , Kaufman Gregory , Patnaik Mrinal M. , Hashmi Sharukh , Hogan William J. , Elliott Michelle A. , Wolanskyj Alexandra P. , Liu Shujun , Litzow Mark Robert , Al-Kali Aref 
Published: March 2020

7064 Background: Obesity is a growing medical challenge that has strong association with many comorbid diseases. Body mass index (BMI) is used as one indicator for obesity. A few papers have linked hematological cancers with a worse prognosis if obesity was present. Aim: to study the influence of obesity clinical outcome in patients (pts) with CMML. Methods: A retrospective chart review of pts with CMML at Mayo Clinic Rochester between 1994–2011 was done. BMI was calculated at diagnosis or first time visit. Overweight was defined as BMI ≥25, while obesity as BMI >30. IRB approval was obtained. Comparison between medians was done using Wilcoxon test, while survival estimates were calculated using Kaplan-Meier estimates via JMP software v.9. Results: We found227 pts with a median follow-up of 311 days, 68% of which weremales. Median age was 71 years, hemoglobin 11 gm/dL, white blood cells (WBC) 12x 109/L, and platelets 90x 109/L. Obese pts had a median age of 68 (p=0.0058), hemoglobin 11 gm/dL (p=0.0018), WBC 13.5 x 109/L, platelets 115x109/L (p=0.012), PB blasts 0, bone marrow (BM) blasts 3.5% compared to non-obese pts (73, 10, 11, 78, 0, 3%, respectively). Diploid cytogenetics were similar in both groups (68% vs 64%, respectively, p=0.54). Leukemic transformation into acute myeloid leukemia (LT) was found in 13% vs 10% (p=0.83). Overall response (OR) was 24% and 23%, respectively (p=0.2), when limited to hypomethylating agents OR was 33% vs 27%, respectively (p=0.62). Median OS was found to be similar (571 day vs 569 days, respectively, p=0.56). When compared, overweight pts had similar outcome to non-overweight. Median LT was 11% vs 15% respectively, OR was 21% vs 28% respectively (p=0.5), and OS was 571 days vs 549 days respectively (p=0.21). On a multivariate analysis age, hemoglobin, platelets, BM blasts%, gender, and obesity (p=0.048) were of a significant value for OS. Conclusions: When compared, both obesity and overweight did not affect demographic characteristics, overall response, or transformation into AML. When comparing median overall survival, obesity was not a significant factor, possibly due to short follow-up. However, on multivariate analysis obesity did have a negative impact on overall survival.