bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adverse Prognostic Impact of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Patients with Diffuse Large B Cell Lymphoma
Authors: Kong Sun-Young , Lee Hyewon , Sohn Ji Yeon , Eom Hyeon-Seok 
Published: October 2019

Abstract
Neutrophil-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been lightened as a prognostic factor in many types of solid tumor. However, there was a limited report for diffuse large B cell lymphoma (DLBCL). Thus, we investigated the impact of NLR and PLR on prognosis of patients with DLBCL. This study involved 234 DLBCL patients treated by rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) at National Cancer Center, Korea. The median patient age was 57 years, and 135 patients (58%) were men. Clinical characteristics as international prognostic index (IPI) including age, performance, LDH, stage and extra-nodal involvement, were evaluated. NLR and PLR at diagnosis were calculated by CBC data from automated hematologic analyzer XE2100 (Sysmex, Kobe, Japan) or differential count which was done by manually using stained peripheral blood slide when CBC data showed flags in auto-analyzer. Hazard ratios (HRs) were determined in terms of risk for overall survival using Cox proportional hazard regression analysis. The mean percentage of neutrophils and lymphocytes was 60 (range, 5-95) and 12 (2-79), and the number of platelets was 257 × 10^9/L (28-839). The mean and standard deviation of NLR and PLR was 3.62 (±4.77) and 14.7 (±20.16), respectively. IPI and stage were predictors for prognosis (p <0.01), and both NLR and PLR showed significant association with poor prognosis of HRs of 1.14 [95% confidence interval (CI), 1.10 to 1.20] and 1.02 [95%CI, 1.02-1.03]. Although both NLR and PLR represented association with IPI, there were still prognostic impacts as HR of 1.12 and 1.02 with IPI in multivariate analysis. These findings suggest that NRL and PLR may be significant prognostic indicators for patients with DLBCL treated by R-CHOP.

Disclosures
No relevant conflicts of interest to declare.
Development of Non-Hodgkin’s Lymphoma As Second Primary Cancer in Hepatitis C Virus-Infected Patients with a Different Primary Malignancy – a Case Series
Authors: Mahale Parag , Romaguera Jorge , Turturro Francesco , Fowler Nathan , Torres Harrys A. 
Published: October 2019

Abstract
Background: Hepatitis C virus (HCV) is carcinogenic and infected patients are at increased risk of developing hepatocellular carcinoma (HCC) and non-Hodgkin’s lymphoma (NHL). HCC can develop as a as a second primary cancer (SPC) in HCV-infected cancer patients with a nonliver first primary cancer. However, reports on HCV-infected patients who develop NHL as SPC are lacking.
Methods: Records of patients with chronic HCV infection who were seen at MD Anderson Cancer Center, Houston, TX, between 01/2008 - 5/2014 were reviewed. Patients who developed NHL in the setting of a different primary malignancy were described in this case series. HCV therapy did not include newly approved antivirals.
Results: Eighty four patients with HCV-associated NHL were seen during the study period. Among, them, six (7%) developed NHL as SPC; most were men (n=4; 67%), Caucasians (n=5; 83%), and had genotype 1 infection (two patients had genotype known; both had genotype 1b infection). All patients had solid first primary cancers, mostly prostate cancer (n=3; 50%), followed by choriocarcinoma (n=1; 17%), chondrosarcoma (n=1; 17%), and squamous cell carcinoma of larynx (n=1; 17%). Most patients (n=5; 83%) had their first primary cancers in complete remission, and only 1 had cirrhosis at lymphoma diagnosis. Surgery (n=3; 50%) and chemotherapy (n=2; 34%) were the main treatment modalities for first primary malignancies, with leuprolide acetate and carboplatin as the only chemotherapeutic agents administered. The types of NHL developed as SPC were diffuse large B cell lymphoma (n=3; 50%), marginal zone B cell lymphoma (n=2; 33%), and mantle cell lymphoma (n=1; 17%). None of the patients had a family history of lymphoma. NHL was not suspected and was found incidentally in all patients at a median of 34 months (range, 2 – 410 months) after the diagnosis of the first primary malignancy. Hepatitis B core antibodies were detected in 4 (67%) patients. A majority of patients had persistent HCV viremia (n=4; 67%) when NHL was diagnosed. Two of the 3 patients who were treated for HCV infection had attained sustained virological response (regarded as virological cure).
Conclusions: NHL may develop as SPC in HCV-infected patients with a different primary malignancy, especially in patients who have primary solid tumors or unresolved infection. Therefore, surveillance not only for the development of HCC but also NHL as SPCs should be continued in HCV-infected patients with different primary malignancy. Eradication of this carcinogenic virus with better tolerated and more efficacious antivirals may potentially reduce the risk of NHL development as SPC.

Disclosures
Torres: Gilead Sciences: Consultancy; Merck & Co., Inc. : Consultancy, Research Funding; Vertex Pharmaceuticals: Consultancy, Research Funding; Genentech,: Consultancy.
Bleomycin Pulmonary Toxicity in Adult Saudi Patients with Hodgkin’s Lymphoma
Authors: Al-Mansour Mubarak M , Al-jizani Wafa A , Al-fayea Turki , Ruaa Shafi , Kazkaz Ghieth A , Bayer Ali M , AL-Foheidi Meteb , Ibrahim Ezzeldin M 
Published: October 2019

Abstract
Background: Bleomycin pulmonary toxicity (BPT) has been well described in Hodgkin's lymphoma (HL) patients treated with bleomycin-containing chemotherapy regimens. As the effects of genetic susceptibility or race on the development of BPT are largely unknown, we intended to examine BPT incidence, risk factors, and its effects on survival in a series of newly diagnosed Saudi Arabian adult HL patients receiving first-line bleomycin-containing chemotherapy.
Methods: We carried out a retrospective review of the relevant records of 164 consecutive eligible adult HL patients treated at two centers.
Results: BPT was observed in 24 of 164 patients (15%) at a median duration of 4.3 months (range, 1 to 58 months). Older age and history of concomitant lung disease were significantly associated with approximately three- (odds ratio [OR] = 3.38; 95% confidence interval [CI], 1.25-9.13; P = 0.02) and seven-fold (OR = 7.19; 95% CI, 2.64-19.54; P <0.0001) increase in BPT risk, respectively. While more patients in non-BPT group achieved CR as compared with BPT patients (93% vs. 79%; P = 0.048), the actuarial 5-year progression-free (82% vs. 63%; P = 0.29) and overall survival (OS) (94% vs. 76%; P = 0.059) for BPT and non-BPT groups, respectively were not significantly different. Nevertheless, in a multivariate analysis, the earlier incidence time of BPT considered as a time-dependent covariate was the only factor that independently influenced OS (hazard ratio = 0.99; 95% CI, 0.99-1.00; P = 0.002).
Conclusion: In Saudi Arabian adult HL patients, the risk of BPT and its effect on survival outcome were comparable to that reported from developed countries. Earlier incidence time of BPT aversely influenced OS. Future studies should consider testing the efficacy and safety of non-bleomycin-containing regimens in HL.

Disclosures
No relevant conflicts of interest to declare.
Generic Imatinib in a Patients with Chronic Myeloid Leukemia in Chronic Phase- a Single Centre Experience
Authors: Urosevic Ivana M , Dokic Marina , Savic Ivanka , Savic Aleksandar , Milosevic Ivana , Rajic Nebojsa , Andjelkovic Nebojsa V. , Sekulic Borivoj , Vlaisavljevic Nada V 
Published: October 2019

Abstract
Imatinib (Gleevec) has shown long-term efficancy and safety in published randomized clinical trials. Anzovip (Imatinib) is a new generic drug produced by Zdravlje Actavis,which was approved by the Medicines and Medical Devices Agency of Serbia in January 2012. In July 2012, National Health Insurance Fund of Serbia introduced this drug in the positive list. All the patients using Glivec were switched to Anzovip and all newly diagnosed patients started with Anzovip therapy. In this study, hematologic and cytogenetic responses were evaluated in CML patients who received generic Imatinib as the first line therapy and in patients who switched from branded Imatinib to an Imatinib copy drug.
Materials and methods. During August and September 2012, all the patients were switched from Glivec to Anzovip and all new CML patients were treated with Imatinib copy. 55 patients treated with branded Imatinib were switched to generic Imatinib. Out of 17 newly diagnosed patients with CML-CP, who started with generic Imatinib, 7 patients could be followed up for 18 months. All patients underwent hematologic, cytogenetic monitoring based of the recommendations of the ELN.
Results. These are the results of using Anzovip after 18 months. Of the 55 patients who were switched from branded Imatinib to Imatinib copy, 11 patients (20 %) have lost complete cytogenetic response they already had, but without signs of biological illness transformation. They were switched to 2nd line therapy nilotinib.Of the 7 newly diagnosed patients who started with genereic Imatinib, all 7 patients (100%) have achieved complete hematologic response (CHR) in the period of 6 months. 3 (42,8%) patients have achieved CCgR and 2 patients (28,6%) have achieved MMR in the period of 12 months. 57% of patients have switched to second generation of TKI because of failure or intolerance according to ELN and national recommendation. The drug has been well tolerated, wild mild adverse event, more frequently, fluid retention and gastrointestinal symptoms. Only one patient have had skin changes grade ¾ and he has been switched to second generation of TKI.
Conclusions. It is unknown whether patients, who responded to branded Imatinib and than switched to its copy versions, will tolerate the copy drug and maintain the previous response. Because of that, it is important to careful follow up of a selected patients several months after the switch to generic imatinib. Despite of the small number of patients who started with Imatinib copy, our results in term of hematologic and cytogenetic response were close to the international series.

Disclosures
Urosevic: Novartis: Consultancy, Honoraria. Savic:Roche: Honoraria; NovoNordisc: Honoraria. Rajic:NovoNordisc: Honoraria.
Mantle Cell Lymphoma, Rare Lymphoma Entity: A Result of Lymphoma Registry in Thailand
Authors: Kanitsap Nonglak , Wannissorn Naree , Lekhakula Arnuparp , Julamanee Jakrawadee , Khuhapinant Archrob , Sirijerachai Chittima , Chansung Kanchana , Norasetthada Lalita , Nawarawong Weerasak , Chuncharunee Suporn , Niparuck Pimjai , Wudhikarn Kitsada , Bunworasate Udomsak , Numbenjapon Tontanai , Prayongratana Kannadit , Wongkhantee Somchai , Wong Peerapon , Suwanban Tawatchai , Makruasi Nisa , Intragumtornchai Tanin 
Published: October 2019

Abstract
Introduction: Mantle cell lymphoma (MCL) is a relatively rare and aggressive mature B-cell non-Hodgkin lymphoma (NHL) entity, encounting for 3-10% of newly diagnosed patients. The purpose of the study is to analyse the incidence, clinical features and outcomes of Thai patients with MCL and compare data with those of Western countries.
Patients and methods: From the nationwide multicenter registry of 4,056 newly diagnosed NHL patients in Thailand between 2007-2014, patients with MCL were identified according to the criteria of diagnosis by WHO classification of lymphoid disorders, 2008. The incidence, baseline clinical characteristics and outcomes were then analysed.
Results: Ninety-nine patients (2.4%) were found to have MCL. The median age was 59.8 years (range 33-86). Seventy-nine percent of patients were men. The primary sites of disease were lymph nodes (60%), bone marrow (19%), GI tract (9%), Waldeyer's ring (4%), sinonasal area (2%) and miscellaneous (6%). (Figure 1). Eighty-three percent of the patients had stage III/IV. Eighty-one patients (82%) received chemotherapy (60.5% with CHOP or CHOP-like chemotherapy, 30.9% with HyperCVAD, and 26% with rituximab-based). Other received palliative chemotherapy or did not receive any. At a median follow-up time of 42 months, the median survival was 30 months (range, 1-94 months). By using Cox analysis, only Ann Arbor stage had impact on overall survival.
Conclusion: MCL is less frequent in Thailand compare to the Western countries. The long-term survival is also much inferior reflecting the limited access to rituximab as well as the high intensity therapy in treating MCL in Thailand.
Table 1. Comparison of MCL patients according to treatment modalities Clinical characteristics (Total 81 cases) CHOP-like (n=49 ) High intensity CMT (n = 25 ) CVP or palliative CMT (n = 7 ) p-value No R 33 19 4 - Age > 60 19 (67%) 6 (24%) 5 (71%) - Stage III-IV 42 (85.7%) 21 (84%) 7 (100%) - Response Overall response Complete response 26 (53.1%) 19 (38.8%) 17 (68%) 11 (44%) 6 (85.7%) 3 (42.8%) - Survival Mean OS (months) (Min-Max) 3yr-OS 5yr-OS 26.8 (0.1-83) 52.2% 52.2% 38.8 (0.8-93.9) 51% 38.1% 34.3 (10.7-70.5) 51% 30.2% 0.44 0.44
Figure 1. Biopsy sites Figure 1. Biopsy sites Figure 2. The Kaplan-Meier plots of OS according to treatment groups Figure 2. The Kaplan-Meier plots of OS according to treatment groups Figure 3. The Kaplan-Meier plots of OS according to tretment with rituximab Figure 3. The Kaplan-Meier plots of OS according to tretment with rituximab

Disclosures
Khuhapinant: Roche: Honoraria.
Investigation of Two Combination HbF Induction Regimens, RN-1 and Hydroxyurea Versus RN-1 and Decitabine, in a Humanized Sickle Cell Mouse Model
Authors: Jagadeeswaran Ramasamy , Agarwal Yash , Ibanez Vinzon , Ruiz Maria Armila , Vaitkus Kestis , DeSimone Joseph , Lavelle Donald , Rivers Angela 
Published: October 2019

Abstract
Sickle cell disease (SCD) results from the substitution of glutamic acid for valine at the sixth amino acid of β-globin protein, leading to the formation of the abnormal hemoglobin S (HbS). Following deoxygenation in red blood cells (RBCs), HbS forms polymers causing the RBCs to become deformed and adherent leading to vaso-occlusive events resulting in splenic infarction, kidney failure, stroke, painful crises, chronic anemia, inflammation and decreased survival. Hydroxyurea, the only drug currently FDA approved for SCD, is not effective in some patients and, therefore, new combination regimens are needed. RN-1, a new drug targeting the histone demethylase LSD-1, is a more effective inducer of γ-globin expression in sickle cell mice and HbF in baboons (P. anubis). Decitabine(DAC), a DNMT1 inhibitor, is well known to induce high levels of HbF in non-human primates and SCD patients and is currently in clinical trials. We investigated the effect of two combination regimens: RN-1 in combination with hydroxyurea vs. RN-1 in combination with DAC. The knock-in humanized sickle cell mice (B6;129-Hbatm1(HBA)Tow Hbbtm2(HBG1,HBB*)Tow/J) were treated with 1) DMSO (vehicle control), 2) RN-1 (5mg/kg), 3) DAC(0.25mg/kg) and 4) RN-1(5mg/kg) + DAC(0.5mg/kg) for 10 days. Analysis of F-retics and γ-globin mRNA performed on d10 showed F-retics were increased two fold (p=0.01) in mice treated with RN-1(5mg/kg) or DAC(0.25mg/kg) compared to DMSO-treated. γ-globin mRNA levels (γ/γ+β) were increased three fold in RN-1(5mg/kg) or DAC(0.25mg/kg) compared to DMSO. The combination of RN-1(5mg/kg) and DAC(0.25mg/kg) did increase F-retics and mRNA levels compared to mice treated with RN-1 alone(p=0.02). Also, the RN-1 and DAC combination led to neutropenia and thrombocytopenia. We next examined the effect of RN-1(5mg/kg) and HU (100mg/kg) in combination. Knock-in humanized sickle cell mice (B6;129-Hbatm1(HBA)Tow Hbbtm2(HBG1,HBB)Tow/J) were treated with 1) DMSO (vehicle) 2) RN-1(5mg/kg) and 3) RN-1(5mg/kg) + HU (100mg/kg). While RN-1 in combination with HU did not significantly increase F-cells or F-retics, there was a significant decrease in spleen weight [(DMSO: 1.17±0..06g; RN1:0.71± 0.1g; RN1+HU: 0.46±0.05g)(p=0.004:p=0.02)] and percentage of sickle cells in a peripheral blood smear.[(DMSO: 8.4 ±1.3%; RN-1:4.1± 0.2%; RN1+HU: 1.57±0.6%)(p=0.006:p-0.014)]. We conclude that further studies to determine the effect of RN-1 in combination with HU or DAC in the sickle cell mouse model and cultures from sickle cell CD34+ cells are needed to evaluate its potential use in the treatment of sickle cell disease. These results suggest that RN-1 in combination with hydroxyurea may be a useful therapeutic regimen.

Disclosures
No relevant conflicts of interest to declare.
Effect of PSI697, a Small Molecule Inhibitor of P-Selectin, in the Townes Model of Sickle Cell Disease
Authors: Jasuja Reema , Hett Sunita Patel , Kaila Neelu , Pittman Debra 
Published: October 2019

Abstract
Chronic vaso-occlusion is a major cause of morbidity and mortality in patients with sickle cell disease (SCD). Persistent vaso-occlusion can damage lungs, liver, kidneys or brain and ultimately lead to end-organ dysfunction. Vaso-occlusive pain crisis is a complex multistep process, initiated by adhesion of fragile sickle erythrocytes and rigid neutrophils to hypoxic and inflamed endothelium. Large multicellular aggregates of blood cells, including platelets and sickled erythrocytes, form on these adherent activated neutrophils in the microcirculation, ultimately causing vascular occlusion and tissue ischemia. Inflammatory mediators, such as P-selectin, play a key role in mediating these heterocellular interactions and attract additional leucocytes to the site of occlusion. P- and E-selectin mediate rolling and tethering of blood cells on the endothelium. Here, we explore cellular and animal models of sickle cell disease to assess PSI-697, an orally active small molecule antagonist of P-selectin. PSI-697 inhibits P-selectin binding to P-selectin glycoprotein ligand-1 (PSGL-1) with an IC50 of 50-125 µM (Bedard et al, JPET, 2008). Townes SCD mice were used to assess the efficacy for PSI-697 in preventing vaso-occlusion in SCD. Mice were randomized to treatment with vehicle or PSI-697. Animals were treated in a prophylactic setting prior to the surgical preparation. Surgical preparation induces a well described acute inflammatory response in the microcirculation associated with neutrophil adhesion to the endothelium and formation of multicellular aggregates. Alexa-488 labeled Ly-6G neutrophil antibody and Dylight-649 labeled CD42c platelet antibody were injected to quantify adherent neutrophils and neutrophil-platelet aggregates. Cremaster microvasculature was observed by intravital microscopy. Mice treated with 100 mg/kg of P-selectin inhibitor PSI-697 showed a 55% reduction in adherent neutrophils and a 78% decrease in the number of neutrophil-platelet aggregates compared to vehicle treated animals. Neutrophils showed ~7 fold increase in rolling velocity in mice treated with P-selectin inhibitor. Our results demonstrate that prophylactic administration of PSI-697, a small molecule P-selectin antagonist, improved parameters associated with vaso-occlusion in Townes SCD mice.

Disclosures
No relevant conflicts of interest to declare.
Pain Experiences in Children with Sickle Cell Disease in the Era of Hydroxyurea
Authors: Kavanagh Patricia , Sprinz Philippa G. , Libernays Evelyn , Pavlus Nicole , Wang C. Jason 
Published: October 2019

Abstract
Background: Pain is the most common complication of sickle cell disease (SCD), and pain diaries are an effective way to capture pain experienced by both children and adults for many conditions, including SCD. The most recent data on pain experienced by children with SCD outside the clinical trial setting, particularly those with Hemoglobin (Hb) SS disease, were collected prior to the publication of the Baby-HUG trial in 2011, which found hydroxyurea to be safe for use in early childhood. One study found that school-aged children with SCD had at least one pain episode per month; another longitudinal study reported that SCD-related pain was experienced by children on 8% of pain diary days. In the era of hydroxyurea use in children, the occurrence of SCD-related pain episodes in children has not been well studied, especially among those with Hb SS disease.
Methods: Parent/child dyads were recruited for a 6-month pilot study of the use of home pain plans and pain diaries from a pediatric hematology clinic based in a safety net institution. The study ran from February to November 2014. Dyads were eligible if the child with SCD was aged 5-15 years and had at least one episode of pain in the year prior to enrollment, by parent report. Parents and children were asked to fill out the diary each day. They received weekly phone calls for the first month, then monthly phone calls until the close of the study, to remind them to complete the daily pain diary and mail it back monthly; $20 gift cards were given for each diary returned. We excluded data from dyads that recorded less than 4 weeks of pain diary data.
Results: Thirty-six parent/child dyads were approached and 30 (83%) consented to enroll in the study. Twenty-six (87%) dyads recorded at least four weeks of data. The average age of the child with SCD was 10.3 ± 3.0 years and 20 (77%) were insured through Medicaid. Twenty-two (85%) children had Hb SS disease, of whom 21 were prescribed hydroxyurea. Data were recorded per dyad on average 135 ± 46 diary days. One child with Hb SS disease reported no pain during the study period. The remaining 25 children had any pain and SCD-related pain an average of 8% and 4% diary days, respectively. Nearly all children reporting non-SCD-related pain had headache or abdominal pain. Ten (38%) children missed at least one day of school during the study period.
Conclusions: In thissample of children with SCD, composed predominantly of those with Hb SS disease prescribed hydroxyurea, pain was an infrequent occurrence and was attributed to SCD only half the time. This study suggests that SCD-related pain experienced by children may be lower than previously reported. Further study is warranted, especially among those prescribed hydroxyurea.

Disclosures
No relevant conflicts of interest to declare.