bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conceptual model of chronic lymphocytic leukemia.
Authors: Chung Helena , Blowfield Matthew , Krogh Calvin , Eek Daniel 
Published: March 2020

e19001 Background: The study aimed to create a conceptual model (CM) of disease- and treatment-related signs, symptoms and impacts in patients with first-line (1L) or relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Methods: The CM was based on literature searches, review of CLL patient blogs/forums, interviews with expert hematologists, and semi-structured concept elicitation interviews with 40 patients with CLL (20 1L, 20 R/R; with fatigue, weight loss, fever and/or night sweats in previous week). To identify salient concepts, the number of patients mentioning each concept and the concept’s mean disturbance rating (from 0 [not at all] to 10 [very]) were mapped. Results: Literature searches identified 32 prevalent concepts, with the most common being fatigue/tiredness. Patient blogs/forums revealed further symptoms (muscle/joint aches, headaches, weakness) and impacts (stress, fear of death, uncertainty). Clinicians reported recurrent infections and swollen lymph nodes as key signs of CLL and noted that fatigue is related to both symptoms (e.g. tiredness) and impacts (e.g. needing to rest and limit daily activities). In patient interviews, 50 concepts were revealed, with 42 present in both 1L and R/R; fatigue was the most prominent and impactful. Fatigue-related sub-concepts were identified, covering symptoms (tiredness/need to sleep, lack of energy, weakness, cognitive fatigue) and impacts (decreased ability to maintain social/familial/professional role, decreased physical functioning, frustration). Three versions of the CM were created: an overall model with all identified concepts, and two models highlighting the most salient concepts in 1L and R/R. Muscle/joint aches, night sweats, bruising, fatigue-related symptoms, fever and recurrent infections/illness were salient symptoms in both 1L and R/R, as were impacts such as anxiety/worry, stress, depression, financial difficulty, and fear of death. Shortness of breath and coughing were salient in 1L only, and swollen lymph nodes, headaches, pain/discomfort, weight loss, nausea/vomiting, and infusion reactions were salient in R/R only. Conclusions: The three versions of the CM can help to inform patient-centered end points to evaluate new treatments for 1L and/or R/R CLL.
Long-term effects of ibrutinib on blood pressure in patients with chronic lymphocytic leukemia (CLL).
Authors: Jones Jade , George Binsah , Peterson Christine B , Burger Jan Andreas , Jain Nitin , Wierda William G. , Keating Michael J. , Durand Jean-Bernard , Ferrajoli Alessandra 
Published: March 2020

e19009 Background: Ibrutinb is approved for treatment of CLL. Hypertension (HTN) has been reported as a side effect of ibrutinib in 1-23% of patients. We previously reported HTN in CLL patients after 6 months of treatment with ibrutinib. In this study we describe the effects of long-term treatment with ibrutinib on blood pressure (BP). Methods: We performed a retrospective study, evaluating 150 CLL patients on ibrutinib-based clinical trials from 2010 to 2015. Patient demographics, co-morbidities, tobacco use, anti-HTN therapy were recorded. BP was evaluated at baseline and sequentially for up to 5 yrs. New onset HTN was defined as systolic BP (SBP) of ≥ 130 mmHg and/or diastolic BP (DBP) ≥ 80 on two separate visits with no prior HTN or anti-HTN therapy. An increase in baseline SBP by ≥10 and/or increase in DBP by ≥10 was considered significant regardless of the absolute BP. Univariate logistic regression analysis was performed to assess relationship of HTN risk factors and new HTN. Results: Patients’ median age was 65 yrs (68% male and 88% white). Median follow-up was 3 yrs. Pre-existing HTN was present in 44% of patients, 40% were on anti-HTN therapy prior to ibrutinib. New HTN developed in 65% of patients without prior diagnosis of HTN; 32 % of patients were started on anti-HTN therapy or received additional anti-HTN therapy. Of the patients who experienced an increase in BP, 33% experienced isolated systolic HTN. Median SBP was 130 at baseline, 132 at 1mo, 137 at 3mo, 135 at 6mo, 139 at 12mo, 138 at 3yrs, 144 at 5yrs (mean increase in SBP: 7.2, P < 0.001). In patients whose SBP was < 130 at baseline the median SBP was 119 at baseline, 122 at 1mo, 134 at 3mo, 130 at 6mo, 134 at 12mo, 135 at 3yrs and 141 at 5yrs (mean increase in SBP: 15.7, p < 0.001). 74% of patients experienced and increase in SBP ≥10. New HTN on ibrutinib was not associated with: tobacco use, obesity, chronic kidney disease or obstructive sleep apnea (p > 0.05). Conclusions: In this study we demonstrated a high rate of new HTN in patients on prolonged ibrutinib treatment. HTN in these patients is persistent, linear and independent of other risk factors. The increase in BP remained despite initiation of anti-HTN therapy. Additional studies are ongoing to define cardiovascular and renal complications associated with HTN in these patients.
Retrospective comparison of Cheson 2007 and Lugano classification criteria in independent review assessment of FDG-avid lymphomas.
Authors: Narang Jayant , Bajpai Surabhi , Jarecha Rudresh , Karve Sayali , Ludajic Katarina , Sharma Manish , Bohnsack Oliver 
Published: March 2020

e19015 Background: Revised Response Criteria in Malignant Lymphoma (Cheson 2007) and Lugano Classification are the most commonly used guidelines to assess response to treatment in lymphoma in clinical trials. While not drastically different from Cheson 2007, important clarifications and modifications were provided in Lugano Classification, specifically in the use of PET in response assessments. Methods: We retrospectively compared the blinded independent review of 25 subjects across multiple studies, assessed using Cheson 2007 and Lugano Classification on separate case report forms by the same reviewer per subject on 2 different dates. Focus was given on comparison of endpoint assessments of Progression-Free Survival (PFS), Duration of Complete Response (DOCR) and Duration of Response (DOR). Results: Assessments using Lugano Classification showed increased DOCR in 12% (3 out of 25), and DOR in 24% (6 out of 25) of the subjects. Cheson 2007 showed better DOR in 8% (2 out of 25) of the subjects. For PET positivity, Lugano Classification requires comparison with liver and mediastinal blood pool, whereas Cheson 2007 requires comparison to background or mediastinal blood pool. The results suggest that this difference in assessment of PET positivity (blood pool versus liver) leads to achieving Complete Response (CR) earlier, leading to longer DOCR and DOR when assessed using Lugano Classification compared to Cheson 2007. Lugano Classification also showed longer PFS in 16% (4 out of 25) of the subjects. When Progressive Disease (PD) was due to identification of new lesion(s), the two criteria showed similar PFS; however, when PD was due to lesion measurements and PET positivity assessment, Lugano Classification showed a longer PFS. Better PFS in Lugano Classification was observed because enlarging lymph nodes do not always show increased PET activity. Conclusions: In Independent review assessments for FDG avid lymphoma, using Lugano Classification showed better DOCR, DOR and PFS as compared to Cheson 2007. Further studies with increased number of subjects and intra-reader variability assessments are warranted to investigate the two criteria.
Hodgkin lymphoma in United Arab Emirates UAE, epidemeology, histological types and treatments outcome: Case series of 47 cases from Mafraq Hospital, Abu Dhabi, UAE.
Authors: Maarraoui Aladdin , AlMessabi Ahmed , Al Teneji Omar , Maarraoui Yasmeen 
Published: March 2020

e19016 Background: Approximately 9,050 Americans gets diagnosed annually with Hodgkin's Lymphoma HL and approximately 1,150 dies each year from HL(1).Nodular Lymphocyte-predominant LP (NLPHL) represents 5% of HL (2). Mafraq Hospital is a tertiary hospital in Abu Dhabi, UAE, We suspected that we are seeing more than expected cases of NLPHL.Therefore, we carried a retrospective study to review all cases of HL seen at our oncology unit for the period from 01/01/2016 till 30/06/ 2018. Methods: We developed Excel data collection tool. After Ethics approval, Electronic Medical Records of all cases seen with the diagnosis of HL between 01/2016 and 06/2018 at Mafraq Hospital were reviewed. Results: Total of 47 case were collected. 8 cases (17%) were found to have NLPHL, The rest of cohort were 39 cases, 22 (57%) of them had nodular sclerosis HL, 4 cases (10%) mixed cellularity HL, 2 (5%) lymphocyte rich HL, no cases of lymphocyte depleted HL. 9 (23%) of cases were classical HL with no type as diagnosis was made from core biopsies. 2 cases (5%) unlisted type.The stage for the 42 case were as follows Stage I: 1 case = 2.3%, Stage II: 24 case = 57.1%Stage III: 11 case = 26.1%Stage IV: 6 cases = 14.2%. Conclusions: We saw 23 (49%) females and 24 (51%) males. Our hypothesis that NLPHL is more frequently seen in UAE seems to be correct as 17% of all HL cases seen were from this subtype. Mean age at diagnosis of all HL cases is 33 years. In the NLPHL there were 2 (25%) females and 6 (75%) males. Mean age at diagnosis for NLPHL is 31.8 years. Most HL patients received ABVD as first line regimen. This is documented in 38 out of 47 case. Mean overall survival registered at the closure of the study is 45 months. It is important that this overall survival is premature as no patient has relapsed or died.
Disease characteristics of diffuse large B-cell lymphoma predicting relapse after autologous stem cell transplantation.
Authors: Gaut Daria , Oveisi David , Howell Grant , Romero Tahmineh , Schiller Gary J. 
Published: March 2020

e19030 Background: High-dose chemotherapy followed by autologous stem cell transplantation (HDC/ASCT) is standard of care for patients with diffuse large B-cell lymphoma (DLBCL) whose diseases relapse after, or are refractory to, first-line therapy. However, there are still high rates of relapse following ASCT, and non-relapse mortality also affects survival rates. Prognostic indicators are therefore needed to identify the best candidates for HDC/ASCT. Methods: We retrospectively analyzed medical records of 111 DLBCL patients (78 relapsed, 33 refractory) who underwent HDC/ASCT at the University of California Los Angeles from 2010-2015. Results: The median age at the time of ASCT was 61 years (IQR 51.5-68.0). 80 patients (72%) had DLBCL in a complete response at the time of ASCT, and the majority (98 patients, 88%) had ECOG performance status of 0-1. After a median follow-up of 4.6 years (IQR 2.2-8.1), the 1-year progression-free survival (PFS) rate was 77.3% (95% CI 69.7%-85.7%) and the 1-year overall survival (OS) rate was 84.7% (95% CI 78.2%-91.7%). 41 patients (37%) relapsed after ASCT with a median PFS of 11 months (IQR 5.0-20.0). 37 patients (33%) died, 23 (21%) from relapse mortality, 11 (10%) from non-relapse mortality, and 3 (3%) from unknown cause of death. In univariate analysis, 2 variables were significantly associated with curtailed PFS and OS: higher number (≥ 3 vs < 3) of chemotherapy regimens prior to ASCT (HR 2.20, 95% CI 1.19-4.06, p = 0.013 for PFS; HR 2.01, 95% CI 1.06-3.84, p = 0.036 for OS) and higher International Prognostic Index (IPI) score at time of ASCT (trend HR 1.61, 95% CI 1.10-2.35, p = 0.018 for PFS; trend HR 2.02, 95% CI 1.37-2.98, p = 0.001 for OS). Higher National Comprehensive Cancer Network (NCCN) IPI score at time of ASCT (trend HR 2.29, 95% CI 1.34-3.90, p = 0.002) and refractory versus relapsed disease (HR 1.99, 95% CI 1.04-3.82, p = 0.038) were also significantly associated with curtailed OS. Conclusions: Our study suggests that IPI, while a validated prognostic tool at diagnosis, is also a prognostic indicator at time of ASCT for PFS and OS. NCCN IPI at time of ASCT was also found to be predictive of OS. Age-adjusted IPI was not associated with outcome following ASCT.
Efficacy of mogamulizumab in previously treated patients with less advanced mycosis fungoides: Results from the MAVORIC study.
Authors: Geskin Larisa J. , Scarisbrick Julia , Bagot Martine , Fisher David Christopher , Elmets Craig , Duvic Madeleine , Beylot-Barry Marie , Kim Ellen J. , Moriya Junji , Leoni Mollie , Zinzani Pier Luigi 
Published: March 2020

e19031 Background: In the MAVORIC Phase 3 study, patients (pts) with previously treated mycosis fungoides (MF)/Sezary syndrome (SS) stage IB-IVB who received mogamulizumab (MOGA) had significantly prolonged progression-free survival and greater overall response rates (ORR) compared to pts on vorinostat (VORI) (Kim et al. Lancet Oncol 2018). Less advanced MF (stage IB/IIA) is a chronic skin malignancy that can involve blood and nodes and may require many lines of systemic therapy over the disease course. This post-hoc analysis specifically examined efficacy and safety of the recently approved MOGA in stage IB/IIA MF pts. Methods: In MAVORIC, stage IB-IVB MF/SS pts who were treated with ≥1 prior systemic therapy were randomized to MOGA or oral VORI. In the post-hoc analysis, time to next treatment (TTNT) was defined as time to any therapy excluding topical steroids or focal radiation treatment. ORR was based on global composite response in 4 disease compartments – skin, blood, lymph nodes, and viscera – achieved at 2 consecutive visits at least 8 weeks apart. Individual compartment responses were also assessed. Results: A total of 85 pts with stage IB/IIA MF were included (MOGA, IB n = 15, IIA n = 21; VORI, IB n = 27, IIA n = 22). Overall, 24% (10/42) of IB pts and 28% (12/43) of IIA pts had received ≥6 prior therapies. Median TTNT with MOGA in IB pts was 11.5 months (mo) (95% CI, 1.4,16.0) compared to 3.1 mo (95% CI, 2.7, 5.3) with VORI; in IIA pts, median TTNT was 10.1 mo (95% CI, 5.5, 12.6) and 4.9 mo (95% CI, 2.4, 8.0), respectively. ORR in IB pts receiving MOGA and VORI was 20% (3/15) and 18.5% (5/27), respectively; ORR in IIA was 19% (4/21) and 0% (0/22), respectively. With respect to stage IB and IIA, compartmental response rates with MOGA were: skin (20% [3/15], 38% [8/21]), blood (0% [0/2], 75% [6/8]), and lymph node (0% [0/0], 15% [3/20]), respectively. Adverse events were generally manageable and consistent with the ITT population. Conclusions: Though MAVORIC was not powered to determine treatment effect by disease stage, this post-hoc analysis of TTNT, ORR, and compartmental response in stage IB/IIA demonstrates meaningful clinical benefit with MOGA in previously treated, less advanced MF pts. Clinical trial information: NCT01728805.
Clinical characteristics and prognosis of primary breast lymphoma: Cleveland Clinic experience.
Authors: Kewan Tariq Zuheir , Covut Fahrettin , Thapa Bicky , Spiro Timothy Peter , Haddad Abdo S. , Daw Hamed 
Published: March 2020

e19035 Background: Primary Breast lymphoma (PBL) is a rare form of extranodal non-Hodgkin lymphoma (NHL). The majority of PBL are diffuse large B-cell lymphoma (DLBL). Current treatments can achieve an overall survival of 5 years in 80% of the patients. We evaluated prognostic factors and survival rates in PBL patients at Cleveland clinic foundation (CCF). Methods: We retrospectively identified patients diagnosed with PBL at CCF between January 2004 and January 2018. Baseline characteristics were compared between the indolent and aggressive lymphoma groups using two sample T-test for continuous variables, chi-square test and fisher’s exact test for categorical variables. Overall survival (OS) was estimated by the Kaplan-Meier method and compared by the log-rank test. Results: A total of 36 patients with PBL were identified, of whom 35 patients (97.2%) were females with a median age of 66 years (34-95). Of all patients, 23 (63.9%) were indolent lymphoma and 13 (36.1%) were aggressive lymphoma. The most common subtypes were marginal zone lymphoma (33.3%), DLBL (25%) and follicular lymphoma (19.4%). Only 2 patients (5.6%) had implant-associated anaplastic large T-cell lymphoma. There was significant difference in presentation between indolent and aggressive lymphoma patients; 78.3% of indolent lymphoma patients presented with incidental mammogram lesions compared to 30.8% of aggressive lymphoma patients (P-value = .019).Seventy five percent of the patients presented with stage IE, 16.7 % presented with stage IIE and 8.3% presented with stage IV. Treatment received included chemotherapy (55.6%), radiotherapy (47.2%), surgeries (16.7%), and rituximab (80% of patients received chemotherapy). Six patients (16.7%) didn’t receive treatment. Only one patient received central nervous system prophylaxis. Median follow-up of patients was 37.1 months. Three-year OS for patients with indolent and aggressive PBL was 94.4% (95% CI 84.4% - 100%) and 90.9% (95% CI 75.4% - 100%), respectively (p = 0.69). Conclusions: Marginal zone lymphoma was the most common subtype in our cohort. Indolent lymphoma commonly present as incidental mammogram finding. Prognosis of PBL is not affected by histologic subtype, tumor stage and bilateral breast involvement. Current treatments achieve good control of the disease.
Phase 2 study of parsaclisib (INCB050465) for relapsed or refractory diffuse large b-cell lymphoma (DLBCL) (CITADEL-202).
Authors: Coleman Morton , Belada David , Casasnovas René-Olivier , Gressin Rémy , Lee Hui-Peng , Mehta Amitkumar , Munoz Javier , Verhoef Gregor , Corrado Claudia , DeMarini Douglas James , Zhao Wanying , Chen Xuejun , Fay Keith 
Published: March 2020

e19038 Background: Parsaclisib, a potent, highly selective, next-generation PI3Kδ inhibitor, showed preliminary efficacy as monotherapy for relapsed or refractory non-Hodgkin lymphoma, including DLBCL (Abstract 410, ASH 2017), in a phase 1/2 study. This phase 2 study further assessed parsaclisib in patients (pts) with relapsed or refractory DLBCL (NCT02998476). Methods: Pts enrolled into 2 groups (A, Bruton tyrosine kinase [BTK] inhibitor naïve; B, BTK inhibitor experienced) and received oral parsaclisib 20 mg QD for 8 wks, then 20 mg QW. In a planned interim futility analysis conducted in the first 40 pts treated in Group A, if ≤13 (≤32.5%) responded by IRC assessment, Group A was to be terminated. Results: At data cutoff (22 Jun 2018), 60 pts (Group A, n = 55; Group B, n = 5) were treated (median age, 71 y [range, 36—94]; men, 63.3%; ≥3 prior systemic therapies, 60%). At the planned interim analysis in Group A, ORR (by PET) was 25% (10/40 pts; 5 CMR, 5 PMR); the futility boundary was crossed. At data cutoff, ORR in Group A was 25.5% (14/55 pts; 8 CMR, 6 PMR); median PFS was 2.2 mo (95% CI: 2.0‒4.1); median DOR was 4.5 mo (95% CI: 2.1‒5.1). ORs were observed in germinal center B-cell (GCB) and non-GCB subtypes. ORR in Group B was 20% (1/5 pts; 1 CMR). The most common non-hematologic treatment-emergent adverse events (TEAEs) occurring in > 10% of all pts (all grade [Gr]; Gr 3/4) were rash events (21.7%; 1.7%), colitis/diarrhea events (16.7%; 5%), nausea (16.7%; 0%), cough (15%; 0%), and pyrexia (15%; 8.3%). Gr 3/4 AST and ALT elevations occurred in 5% and 1.7% of pts, respectively; Gr 3/4 neutropenia and anemia occurred in 5% of pts each. The most frequent ( > 5%) serious TEAEs were pyrexia (8.3%), general physical health deterioration (6.7%), and hypercalcemia (6.7%). TEAEs led to therapy discontinuation in 7 pts (2 treatment-related), dose interruption in 20 pts (10 treatment-related), and dose reduction in 3 pts (all treatment-related). Median duration of therapy was 57.5 d (range, 11–318). Conclusions: Parsaclisib monotherapy using a QD followed by QW dosing regimen was well tolerated with no new safety signals reported. Further evaluation of parsaclisib in all subtypes of DLBCL is ongoing in a combination study Clinical trial information: NCT02998476.
Tumor-associated myeloid derived suppressor cells of granulocytic nature as a potential biomarker for prognostication of response in treatment of diffuse large cell lymphoma.
Authors: Mukherjee Kalyan Kusum , Dhar Sukanya , Chakraborty Mohona , Bhattacharjee Rajib , Bhanja Shayani , Das Subhadip , Ghosh Sarbari , Sarkar Madhurima , Dasgupta Shayani , Ghosh Diptendu , Bose Anamika , Baral Rathindranath 
Published: March 2020

e19040 Background: NHL is a type of lymphoma either B or T cell origin. However, 85% is of B cell type, especially diffuse large B cell lymphoma (DLBCL) with CD20+ in nature. Standard of care of CD20+DLBCL is R-CHOP 6 to 8 cycles and 66% patients generally respond to this treatment. Remaining 34% is still unresponsive to R-CHOP. Thus, establishment of a biomarker is required to intensify the treatment.Out of different scope of biomarker development, alterations in immune cellular components within tumor microenvironment may be tried as a potential biomarker to assess the possibility of occurrence of residual disease and relapse within 2 years for the DLBCL patients with 6-8 cycles of R-CHOP. Methods: 51 of selected pt.CD20+ DLBCL were treated with 6-8 cycles of R-CHOP and included in the present study. A panel of immune cells CD4+, CD8+ T cells, CD4+CD25+FoxP3 regulatory T cells, CD33+CD11b+CD14-/+ MDSCs and CD8+CD45RO+ Memory T cells were studied by flow-cytometry at different phases of treatment. Results: Within 51selected patients, 9 were disease free and 11patients exhibited stable disease for 2years (stable, non-relapsed, n = 20) following the completion of treatment. Rest of the patients (n = 31) showed relapse in different time periods within 2 years. Among several immune cells, CD33+CD11b+MDSCs were remarkably elevated in high grade residual and relapsed DLBCL patients compared to non-relapsed patients and normal healthy individuals. CD33+CD14- granulocytic, but not CD33+CD14+ monocytic MDSCs are mostly increased in relapsed patients than those having stable disease. CD4+CD25+FoxP3 regulatory T cells are also elevated in relapsed DLBCL patients, but increment is not comparable as MDSCs. No significant alteration was noticed in CD4+ and CD8+ T cells. Among relapsed patients CD8+CD45RO+ Memory T cells are increased, those are mostly corrupted in nature. Conclusions: Observed correlation between increased granulocytic MDSCs with the occurrence of residual disease and/or relapse suggests granulocytic MDSCs might be a potential biomarker for prediction of residual and relapse for DLBCL patients.