bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics and outcomes of Philadelphia chromosome-negative myeloproliferative neoplasm in a tertiary institute in India: An ambispective study.
Authors: Soti Kamal Raj , Kumar Lalit , Saxena Renu , Bakhshi Sameer , Gogia Ajay , Malik Prabhat Singh , Sahoo Ranjit , Sazawal Sudha 
Published: March 2020

e18553 Background: Philadelphia chromosome (Ph) negative Myeloproliferative neoplasm (MPN) is a rare heterogeneous group of clonal hematological malignancy. We aim to describe the clinico-pathological features, treatment, outcomes and complications of this disorder. Methods: It is an ambispective study. All Ph negative MPN patients registered during 2001 to 31st December 2015 at our institute were reviewed for demographic data, diagnosis based on WHO 2008 criteria, treatment, complications and outcomes. SPSS software was used. Results: There were 55 patients registered with PMF (37), ET (9), PV (7), CNL (1) and MPN-U (1). PMF showed median age 51.2 years (23-70), male: female ratio of 1.46, symptomatic (36), splenomegaly (29), mean hemoglobin 9.7 gm/dl (3-16), JAK2 mutation positive (14), CALR mutation positive (1). Most of the patients were DIPSS intermediate-1 risk 22 (59.4%) grouping. They received hydroxyurea (13), steroids (9), ruxolitinib (6), immunomodulators/steroids (4), aspirin (3), allogeneic stem cell transplantation (2), interferon (1), radiation (1), danazol (1) and observation (1). Median OS was not reached. OS at 5 years is 84% (95% CI 70% to 98%). Survival probability at 36 months is significant for circulating blasts <1% and high bone marrow fibrosis but not significant on multivariate analysis. Progression probability at 36 months is significant for circulating blast <1% and high DIPSS score but not significant in multivariate analysis. PV showed median age 58 years (23-70), male: female ratio 6:1, symptomatic (7), splenomegaly (6), mean hemoglobin 18.4 gm/dl (16.6-21.5), JAK2 mutation positivity (5), low risk (2), high risk (5). They received hydroxyurea (6), phlebotomy (3) and aspirin (1). Five out of 7 patients are in stable condition. ET showed median age 39 years (24-72), male: female ratio 2:1, symptomatic (4), splenomegaly (2), mean hemoglobin 12.2 gm/dl (7.5-15.4), JAK2 mutation positivity (4), low risk (7) and high risk (2). They received aspirin (6), hydroxyurea (5), and observation (1). Three patients are in stable condition. CNL (1) developed pneumothorax and was lost to follow up. MPN-U (1) received hydroxyuea. Seven died due to pneumonia (5), transfusion hypersensitivity (1) and AML transformation (1). Conclusions: PMF is the most common Ph negative MPN in our institute with DIPSS intermediate-1 being the most common risk group. At a median follow up of 36 months overall survival at 5 years is 84%.
Expression and prognostic relevance of calcium calmodulin-dependent protein kinase kinase 2 (CaMKK2) in chronic lymphocytic leukemia (CLL).
Authors: Jauhari Shekeab , Volkheimer Alicia D. , Barak Ian , Guadalupe Eross , Weinberg J. Brice , Chao Nelson Jen An , Li Zhiguo , Racioppi Luigi 
Published: March 2020

e19002 Background: CaMKK2 has restricted tissue expression in humans, regulates diverse cell functions, and is overexpressed in several human malignancies. Blocking its function reduces cancer cell migration and survival in vitro and in vivo. The relevance of CaMKK2 signaling in lymphoma is uncertain, however. Here, we sought to characterize CaMKK2 expression in CLL, as well as its predictive variables and prognostic relevance. Methods: B cell samples from 39 CLL patients and 4 healthy donors were obtained from a biorepository at our institution through an active protocol. Commercially available kits were used for RNA isolation, cDNA generation, and RT-PCR. The Kolmogorov-Smirnov test was used to compare CaMKK2 expression between patients and donors. Regression analysis was used to identify independent predictors of CaMKK2 expression. Treatment-free survival was estimated using the Kaplan-Meier method. Results: CaMKK2 mRNA was standardized to actin and overexpressed in CLL cells v. healthy donor B cells (2.27 - 11.83 x 10-2 v. 0.93 - 1.67 x 10-2, p = 0.0014). Nine variables were evaluated for possible association, including age, gender, race, WBC and monocyte count, IGVH mutation status, FISH panel, Zap70 and CD38 status. By univariate analysis, unmutated IGVH and African-American race were associated with higher CaMKK2 expression (p = 0.0023 and 0.0238). Race was identified as a potential confounder for IGVH mutation status and vice versa. In a multivariate model, only IGVH mutation status predicted for CaMKK2 expression. Patients in the highest quartile of CaMKK2 expression had lower 2 year treatment-free survival compared with all others (10.7% v. 59.2%, p = 0.0054). Conclusions: CaMKK2 mRNA is over-expressed in CLL cells relative to normal B cells. Higher CaMKK2 expression in CLL may be associated with unmutated IGVH and African-American race and predict shorter time to treatment. Our analyses are limited by all unmutated IGVH patients receiving early treatment in our cohort. [Table: see text]
Impact of absolute lymphocyte count on prognosis of aggressive non-Hodgkin lymphoma.
Authors: Kaur Anahat , Grover Punita , Bulchandani Sheetal , Odeny Thomas A , Madhusudhana Sheshadri , Shrestha Anuj 
Published: March 2020

e19034 Background: Multiple studies have attempted to identify parameters to predict prognosis and overall survival (OS) in Non-Hodgkin Lymphoma (NHL). Revised International Prognostic Index (R-IPI) is commonly used but does not capture all predictive risk factors in the Rituximab era. Low absolute lymphocyte count (ALC) on follow up after first line therapy has been reported to predict relapse. The prognostic value and exact cut off for low ALC at diagnosis is not known. We aimed to investigate whether ALC at time of diagnosis is an independent predictor for OS in aggressive NHL. Methods: We retrospectively evaluated patients with aggressive NHL treated at our center from 1/2000 to 12/2016 with at least 2 year longitudinal follow up after diagnosis. We retrieved data for baseline characteristics including age, sex, Ann Arbor stage, R-IPI score, HIV status, histopathological diagnosis (Diffuse Large B Cell Lymphoma (DLBCL), Burkitt′s lymphoma, Follicular Lymphoma Grade IIIB, high-grade B cell lymphoma), type of chemotherapy and clinical response. Patients were divided into four subgroups based on ALC at diagnosis: < 500, 501-1000, 1001-1500 and > 1500X109/L. Statistical analysis was done using REDCAP and Stata v13. Results: A total of 92 patients were identified. The average age at diagnosis was 53.4 years, 63% were male and 73.5% were diagnosed with DLBCL. Per R-IPI score, 16.3% were high risk, 31.3% were high intermediate risk, 22.5% low intermediate risk and 30% were low risk. The median OS for patients with ALC < 500 x109/L (5.4%) was 1.5 years, ALC 501-1000 (38%) was 2.3 years, ALC 1001-1500 (23.9%) was 4.25 years and ALC > 1500 (32.6%) was 5.2 years. On multivariate analysis this difference was not statistically significant due to small sample size. Conclusions: We found that low ALC at diagnosis trended towards worse OS in aggressive NHL but did not reach statistical significance on multivariate analysis. Our study is limited by retrospective nature and sample size. Multicenter studies need to be done to validate these results. Studies are also needed to know the exact cut off for low ALC. [Table: see text]
Comparison of salvage therapies for relapsed or refractory diffuse large B-cell lymphoma (DLBCL): Network meta-analysis.
Authors: Vosuri Venkata , Kaisreddy Ravi , Bandi Somasekhar 
Published: March 2020

e19037 Background: Salvage chemotherapy followed by autologous stem cell transplantation(ASCT) is the standard second-line treatment for relapsed or refractory diffuse large b-cell lymphoma(DLBCL). Rituximab plus ifosfamide, carboplatin, and etoposide(R-ICE) and rituximab plus dexamethasone, high dose cytarabine, cisplatin(R-DHAP) are the two widely used regimens worldwide but quest for optimal regimen continues. Our objective is to compare currently available salvage therapies based on complete response and adverse events. Methods: Pubmed, EMBASE and Clinicaltrials.gov were queried for salvage therapies in relapsed or refractory DLBCL. Only randomized clinical trials including phase 2 and 3 trials involving salvage therapies for relapsed or refractory DLBCL were selected. Data was extracted based on meta-analysis guidelines by two independent reviewers. Network meta-analyses of treatment effects and adverse outcomes were calculated with a frequentist approach. Results: Overall, 5 studies(1480 patients) were included. The salvage therapies investigated were rituximab plus ifosfamide, carboplatin, and etoposide(R-ICE), rituximab plus dexamethasone, high dose cytarabine, cisplatin(R-DHAP), rituximab plus gemcitabine, dexamethasone, cisplatin(R-GDP), ofatumumab plus dexamethasone, cytarabine, and cisplatin(O-DHAP), ifosfamide plus ofatumunab, carboplatin, and etoposide(O-ICE), dacetuzumab plus rituximab, ifosfamide, carboplatin and etoposide(DR-ICE). Of the 6 regimens in the network, treatment with R-DHAP (OR:0.36,95%CI:0.24-0.54), R-GDP(OR:0.37,95%CI: 0.21-0.65), O-ICE(OR:0.16,95%CI: 0.05-0.53), O-DHAP(OR:0.30,95%CI:0.17-0.52), DR-ICE(OR:0.77,95%CI:0.40-1.49) were not superior against network placebo(R-ICE) in achieving complete response. Higher odds of occurring severe adverse events was observed in R-DHAP(OR:2.02,95%CI: 1.35-3.01) and O-DHAP(OR:2.15,95%CI: 1.24-3.72) salvage regimens when compared to R-ICE. Conclusions: R-DHAP, R-GDP, O-ICE and O-DHAP were found to have no difference in treatment effect in achieving complete response in comparison to R-ICE. R-DHAP and O-DHAP are associated with higher number of severe adverse events in comparison with R-ICE. Outcomes mentioned above should be interpreted in the context of drugs and other factors involved in the disease.
The efficacy of ibrutinib-based combination therapy for mantle cell lymphoma: A systematic review.
Authors: Thirunagari Prem , Siyahian Aida , Iftikhar Ahmad , Wahab Ahsan , Ashraf Afia , Majeed Ammara , Nunes Cavalcante Parr Nadia C , Russ Atlantis Dawn , Kumar Abhijeet , Anwer Faiz 
Published: March 2020

e19043 Background: Mantle Cell Lymphoma (MCL) is generally treated with rituximab (R) in combination with other drugs. However, treatment for relapsed or refractory (RR) MCL is challenging. For Ibrutinib (Ibr), we aim to determine the efficacy in combination therapy for newly diagnosed (ND) and RR MCL. Methods: Per PRISMA guidelines, a systematic review was performed using four databases. Results: Eleven studies with 363 patients were identified, most commonly studied regimens were ibrutinib in combination with R in 2 phase II studies and 2 studies on Ibr in combination with venetoclax. Ibr was also studied as part of the three-drug regimens in combination with bendamustine & R, lenalidomide & R, and obinutuzumab & venetoclax. Ibr was studied in combination with other drugs such as palbociclib, ublituximab, and bortezomib as part of the two-drug regimens. Results summarized in Table. Adverse events included cytopenia, atrial fibrillation, septic shock, tumor lysis syndrome, and GI toxicities. Conclusions: Ibr in combination with R demonstrated the highest overall ORR and CR in treatment of ND MCL, whereas combination with venetoclax and obinutuzumab demonstrated highest overall ORR and CR in treatment of RR MCL. Additional studies are needed to further assess and confirm its role in treatment. [Table: see text]
Survival outcomes in the elderly with limited stage diffuse large B-cell lymphoma treated with chemotherapy: SEER propensity-matched analysis.
Authors: Kaisreddy Ravi , Vosuri Venkata , Bandi Somasekhar 
Published: March 2020

e19046 Background: Current data shows a median age of diffuse large b-cell lymphoma (DLBCL) diagnosis of 70 years. More than 50% of elderly DLBCL patients can be expected to be cured by modern immunochemotherapy. Survival outcomes in elderly patients with limited stage DLBCL treated with chemotherapy outside of clinical trials are poorly characterized. Our objective is to determine survival pattern and factors that influence survival in elderly patients with limited stage DLBCL treated with chemotherapy through analysis of data from a large nationwide cancer registry in modern treatment era. Methods: The Surveillance Epidemiology and End Results (SEER 18) treatment database (2001-2013) was used to detect limited stage (Ann Arbor lymphoma stage I and II) DLBCL (ICD-O-3 code: 9680/3) adult cases with ages between 60-80 years treated with chemotherapy. Patients were divided into two cohorts. Cohort 1 included patients aged ≥60 to 70 yrs and Cohort 2 included patients aged > 70 to 80 yrs. The variable "First Malignant Primary Indicator" was used to differentiate between primary DLBCL and secondary DLBCL cases. Overall survival (OS) was calculated using the Kaplan-Meier methods and multivariate cox regression model to determine the impact of race, gender, radiation use and primary malignant indicator on survival using 1:1 propensity score matching. Chi square test was applied to delineate for any significant difference between two cohorts. Results: Overall, 11138 patients were included with 5569 patients in each cohort. The relative incidence of limited stage secondary DLBCL was greater for cohort 2 when compared to cohort 1 (26% vs. 15%, p < 0.01). The odds of receiving radiation was 27% higher in cohort 1 compared to cohort 2 (p < 0.0001). Compared to cohort 1 (median OS-130 months), cohort 2 had worse median OS of 72 months (p < 0.0001). Female gender, not receiving radiation and secondary status have shown strong relationship with increased risk of death on multivariate cox regression analysis in the elderly limited stage DLBCL patients. Conclusions: Overall survival was worse in age group 70-80 yrs when compared to age group 60-70 yrs in limited stage DLBCL patients treated with chemotherapy. This may be due to differences in treatment approaches. Female gender, not receiving radiation and secondary status are poor prognostic factors of survival in above group of patients. Race has no impact on survival.
Efficacy and safety of PEG-rhG-CSF in primary and secondary prevention of chemotherapy-induced neutropenia.
Authors: Zhu Jun , Li Huiping , Fan Zhengfu , Gao Yunong , Tu Meifeng , Shao Bin , Gao Tian 
Published: March 2020

e19051 Background: This study was to evaluate the efficacy and safety of PEG-rhG-CSF (brand name:jinyouli) in primary and secondary prevention of CIN(chemotherapy-induced neutropenia). Methods: This is a single-center,one-arm clinical study.Patients with non-myeloid malignant tumors were enrolled. PEG-rhG-CSF was given subcutaneously at 24-48h after chemotherapy. The indicator was febrile neutropenia(FN) and IV grade absolute neutrophil count. Results: From January 2016 until June 2018,217 patients were enrolled including 119 lymphoma patients, 50 breast cancer patients, 30 bone tumor patients,18 gynecologic oncology patients, and While146 with primary prevention and 71 with secondary prevention. The incidence of FN was 5.0% (35/692), which was 4.3% (21/478) in the primary prevention patients and 6.5% (14/214) in the secondary prevention patients ( p= 0.233).Logistic regression analysis showed that the longer the treatment cycle, the lower the incidence of FN. Comparison of the indicators of different chemotherapy cycles showed that the IV grade absolute neutrophil count (ANC) reduction was significantly lower in the primary prevention patients than in the secondary prevention patients in the first cycle of chemotherapy[17.1%(25/146) vs.46.5%(33/70),p = 0.000],the incidence of FN and IV grade ANC reduction were significantly lower in the second cycle of treatment than in the first cycle(p < 0.05).The adverse event were mainly bone pain, the incidence of 1/2 grade bone pain was 3.7% (8/217) and the incidence of grade 3/4 bone pain was 1.8% (4/217). Conclusions: The prevention of CIN with PEG-rhG-CSF after chemotherapy can effectively reduce the incidence of FN.For the first chemotherapy cycle, primary prevention is more effective than secondary prevention in preventing the incidence of IV grade ANC reduction. Clinical trial information: NCT02905916.
Distribution and influencing factors of tumor mutational burden in different lymphoma subtypes.
Authors: Zhou Hui , Du Xinhua , Zhao Tingting , Ouyang Zhou , Liu Wei , Deng Mingyang , He Qian , Yi Yuting , Dai Lian , Yang Ling , Xia Xuefeng 
Published: March 2020

e19053 Background: Tumor mutational burden (TMB) has emerged as a promising biomarker in melanoma, NSCLC, glioma, and likely across types of solid cancers. However, TMB distribution and influencing factors in non-Hodgkin's lymphoma are still unknown. Methods: In this study, we focused on tumor (tTMB) and peripheral blood TMB (bTMB) in different lymphoma subtypes and conducted a hybridization-capture methodology and targeted 1.1Mb or 1.7 Mb of genomic coding sequence. Analysis of 188 tumors and 98 plasma samples matching oral epithelial normal samples was performed to characterize the landscape of somatic mutations between the TMB high (TMB-H) and TMB low (TMB-L) groups. Results: In our cohort, tTMB and bTMB ranged from 0 to 42.48, and 0.59 to 37.17, respectively. The top quartile TMB distribution (tTMB:12.34, bTMB:13.20) was used as the cut-off value to define TMB-H. DLBCL had significantly higher tTMB than small B cell lymphoma and peripheral T-cell lymphoma (p < 0.0001). 34.09% of DLBCL had TMB-H, and minority of patients had TMB-H in small B cell lymphoma (3.70%), and peripheral T-cell lymphoma (3.85%). The bTMB had the similar distribution to tTMB. Among all the tumor and plasma samples we detected 8 gene mutations having a significant correlation with high TMB including BTG2, PIM1, DUSP2, HIST1H1E, BTG1, SOCS1, HIST1H1C, CD70 ( p< 0.05) . Table TMB distribution of different lymphoma subtypes Conclusions: Compared to other lymphoma subtypes, DLBCL had higher TMB. Particular gene mutation had correlation with high TMB.[Table: see text]
Impact and influence of PET on imaging related endpoints in patients with Lymphoma using IWG-NHL or Lugano classification.
Authors: Sharma Manish , Bohnsack Oliver , Clark Daniel , O'Connor Michael , Singareddy Anitha , Narang Jayant , Jarecha Rudresh 
Published: March 2020

e19061 Background: Positron Emission Tomography (PET) scans were applied to lymphoma as early as in 1990s. Revised criteria for lymphoma assessment was published in 2007 by International Working Group (IWG). The criteria for PET into response assessment were added due to better sensitivity and superiority of PET over CT and its ability to distinguish between viable tumor and necrosis or fibrosis in residual mass after treatment. PET was primarily recommended for patients with FDG avid curable lymphomas such as Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL) and later for the post-treatment assessment of DLBCL and HL. The Lugano Classification 2014 regarded FDG PET/CT to be the standard for staging and assessment of all FDG-avid histologies. Methods: A retrospective review of 10 Lymphoma studies with a total of 1,537 subjects and 17,394 time points was carried out using PET in addition to CT as per imaging schedule. There were 5 clinical trials with a total of 1,169 subjects with 15,480 time points using IWG-NHL classification 2007 while 5 clinical trials with a total of 729 subjects and 1,914 time points using Lugano classification 2014. The number of subjects and time points with PET where PET had an impact on the overall assessment was calculated. Results: PET was available for a total of 1,159 subjects (out of 1,537) and 4,688 time points (out of 17,394) across all 10 studies. Out of 4,688 visits with PET, 956 (20.4%) visits had an impact on overall assessment due to additional metabolic findings. Out of 1,159 subjects with PET, 462 (39.9%) subjects had an impact on overall assessment and study endpoints due to additional uptake related findings. The impact across different studies was between 7% to 59% possibly due to difference in indication, line of therapy and blinded independent review design. The most common impact due to PET was related to complete response and disease progression. Conclusions: It can be concluded that PET significantly impacts assessments and imaging endpoints for lymphoma clinical trials using IWG-NHL classification or Lugano classification. Thus, addition of PET improves the outcome of the response not only in lymphoma treatment and diagnosis, but also clinical trial outcomes. [Table: see text]
Prognostic factors and nomogram for survival prediction in patients with primary pulmonary lymphoma: A SEER population-based study.
Authors: Low Soon Khai , Tawfik Gehad Mohamed , Zayan Ahmad Helmy , Istanbuly Obaida , Nguyen Tran Minh Duc , Ebied Amr , Lee Shin Yin , Huy Nguyen Tien 
Published: March 2020

e19069 Background: The prognostic factors influencing survival and optimal management of primary pulmonary lymphomas (PPLs) have not been clearly defined due to rarity of the disease. This study sought to characterize the significant prognostic factors of PPL and develop a prognostic nomogram for individualized prediction of survival outcomes in patients with PPL. Methods: Patients diagnosed with PPL between 1983 and 2010 were identified using the Surveillance, Epidemiology, and End Results (SEER) Program database. Kaplan-Meier survival analysis and Cox proportional hazards regression model were performed to identify significant independent prognostic factors for overall survival (OS) in patients with PPL. A nomogram was constructed for the prediction of 5-year OS probability based on these variables. Results: The study cohort of 2325 PPL patients has a 5-year OS rate of 52% and a median OS of 67 months. Older age at diagnosis (HR 1.031; 95% CI, 1.026-1.036; p<0.001], males (HR 1.434; 95% CI, 1.267-1.622; p<0.001), Hispanic race (HR 1.370; 95% CI, 1.113-1.687; p=0.003), non-marginal zone B-cell lymphoma of mucosa associated lymphoid tissue (MALT) histology (p<0.001), primary site at main bronchus (HR 1.326; 95% CI, 1.014-1.735; p=0.039), Ann Arbor stage IV (HR 1.542; 95% CI, 1.324-1.795; p<0.001) were significantly associated with worse OS. All treatment modalities, including chemotherapy (HR 0.615; 95% CI, 0.536-0.706; p<0.001), surgery (HR 0.666;95% CI, 0.577-0.769; p<0.001) and radiotherapy (HR 0.829; 95% CI, 0.693-0.992; p=0.041) were independent predictors of survival. The nomogram constructed using these variables has a higher concordance index of 0.716 (95% CI, 0.699-0.734) compared to that of Ann Arbor staging system [0.571 (95% CI,0.552-0.591); p<0.001]. Conclusions: Older age, male sex, Hispanic race, non-MALT histology, primary site at main bronchus, advanced Ann Arbor stage, not receiving treatment were independent prognostic factors that are associated with worse OS in patients with PPL. The nomogram demonstrated good agreement between the predicted probabilities and actual observations on calibration plots.