bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Lenalidomide on Hepatitis C Viremia in Cancer Patients: A Case Series
Authors: Hosry Jeff , Samaniego Felipe , Turturro Francesco , Economides Minas P. , Torres Harrys A. 
Published: November 2019

Abstract
Background: T cells play an important role in controlling hepatitis C virus (HCV) infection. Immunomodulatory drugs affecting T cells such as thalidomide and lenalidomide are used in the treatment of some hematologic cancers (mainly multiple myeloma). Lenalidomide is up to 1000 times more potent than thalidomide in stimulating T cell proliferation, interferon-γ and interleukin-2 production. HCV reactivation (increase of HCV-RNA by at least 1 log10IU/mL) with hepatitis flare after thalidomide therapy was recently reported (Mahale et al., Open Forum Infect Dis. 2015); however, the effect of lenalidomide on HCV-viremia has not been studied yet.
Methods: HCV-infected cancer patients treated with lenalidomide at MD Anderson Cancer Center (11/2012-3/2016) were studied. HCV-RNA levels were measured before and after lenalidomide use. Since chronically infected patients have stable HCV-RNA levels that only varies ∼0.5 log10 IU/m, a significant change in HCV viremia was defined as a change of HCV-RNA ≥ 1 log10IU/ml from baseline. Hepatitis flare was defined by an increase of ALT level to ≥ 3 times upper limit of normal (or >170 IU/ml).
Results: Five HCV-infected cancer patients treated with lenalidomide were studied. All the patients were males with a median age of 56 years. They had multiple myeloma (n=4) or large B-cell lymphoma (n=1). Four patients had HCV genotype 1 (80%) and 1 had genotype 2 (20%). Two patients (40%) were cirrhotics. The 5 patients studied received 6 different lenalidomide-containing regimens: 2 with lenalidomide monotherapy, 2 lenalidomide + rituximab and 2 lenalidomide + steroids. HCV-RNA levels were measured between week 4 (1, 17%) and week 12 (5, 83%) on lenalidomide treatment. A decrease of HCV-RNA was seen with all the 6 regimens (100%) (Figs 1A, 1B and 1C). Nonetheless, a significant decrease (>1 log10IU/ml) was noted in 4 out of the 6 regimens: two on lenalidomide monotherapy (1.21 and 1.49 log10IU/ml) and two on lenalidomide + rituximab (1.15 and 1.3 log10IU/ml). Hepatitis flare was only seen in one patient treated with lenalidomide + rituximab but he did not have concomitant HCV-RNA changes.
Conclusion: Unlike thalidomide,lenalidomide does not cause HCV reactivation. On the contrary, this agent seems to inhibit HCV replication.
Figure 1 Figure 1.

Disclosures
Samaniego: Karus Therapeutics: Research Funding. Torres:Pfizer: Other: Scientific advisor; Theravance Biopharma: Other: Scientific advisor; Astellas Pharma: Other: Scientific advisor; Novartis: Other: Scientific advisor; Genentech: Other: Scientific advisor; Janssen Pharmaceuticals: Other: Scientific advisor; Vertex Pharmaceuticals: Other: Scientific advisor, Research Funding; Merck & Co.: Other: Scientific advisor, Research Funding; Gilead Sciences: Other: Scientific advisor, Research Funding.
Ticagrelor Modulates Proliferation in Multiple Myeloma Via P1 and P2 Receptor-Mediated Mechanisms
Authors: Meltzer Elan , Mediero Aranzazu , Whatling Carl , Berger Jeffrey S , Cronstein Bruce 
Published: November 2019

Abstract
Background:Multiple Myeloma (MM) is a hematologic malignancy involving uncontrolled proliferation of plasma cells and is particularly trophic to bone where it induces osteoclast-mediated bone destruction. Ticagrelor is a platelet inhibitor that blocks P2Y12 receptors and inhibits ENT1-mediated adenosine uptake, thereby increasing extracellular adenosine, which activates P1 receptors. Prior studies demonstrate that ticagrelor increases life span in a murine model of MM via its effect on extracellular adenosine. Prior studies also demonstrate an increase in proliferation, in vitro, and tumor growth, in vivo, of MM cells in the presence of platelet releasate. Ticagrelor blocks in vitro platelet-stimulated myeloma proliferation, suggesting a positive relationship and interaction between active platelets and multiple myeloma. We therefore determined whether the effect of ticagrelor on myeloma cells was mediated by extra-cellular adenosine or/and inhibition of platelet function.
Methods:Human primary myeloma cells (KMS) were incubated with ticagrelor (10-9-10-4 M) in the presence of 5ng/ml IL-6 in the absence/presence of an A2AR antagonist (ZM241385 10-6M) and platelets (1:500 myeloma cell:platelets). In other experiments MM cells were incubated in the presence of platelet releasate, releasate from platelets treated with ticagrelor, or ticagrelor alone. Proliferation was assayed by Cell Titer MTS assay (Promega).
Results: Ticagrelor inhibited MM cell proliferation by 20% (p<0.0001, IC50=0.5µM). This effect was abrogated by ZM241385 (48±6% increased vs. ticagrelor, p<0.0001). Platelet releasate increased MM proliferation by 33±6% (p<0.05) and ticagrelor inhibited the effect of platelet releasate on MM cell proliferation (IC50=0.12µM).
Conclusions:These results suggest that ticagrelor inhibits proliferation of malignant plasma cells by a mechanism dependent on both adenosine A2A and platelet P2Y12 receptors. Moreover, platelet releasate intensifies proliferation, and this effect is reversed when the P2Y12 receptor is blocked by ticagrelor.
Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3.

Disclosures
Meltzer: NIH: Research Funding; Celgene: Research Funding; AstraZeneca: Research Funding. Mediero:AstraZeneca: Research Funding; Celgene: Research Funding; NIH: Research Funding. Whatling:AstraZeneca: Employment. Berger:Merck: Membership on an entity's Board of Directors or advisory committees; AZ: Research Funding. Cronstein:AstraZeneca: Consultancy, Research Funding; CanFite: Equity Ownership; Gizmo Therapeutics: Consultancy; Eli Lilly & Co.: Consultancy; NIH: Research Funding; Celgene: Research Funding.
Impact of Switching from Intravenous to Subcutaneous Bortezomib in Real Life. Overlapping Toxicity and Efficacy in All Settings of Myeloma Patients Balancing Schedule and Way of Bortezomib Adminisration
Authors: Mangiacavalli Silvia , Cocito Federica , Ferretti Virginia Valeria , Cartia Claudio Salvatore , Ganzetti Maya , Cazzola Mario , Corso Alessandro 
Published: November 2019

Abstract
Background: Bortezomib

Disclosures
Corso: Janssen-Cilag: Honoraria.
Human CMVpp65-Specific Stem Cell-like Memory T-Cells (TSCM) Are a Principal Source for Rapid Repopulation of Immunodominant Central Memory (TCM) and Effector Memory (TEM) in the Circulation
Authors: Kuo Tzu-Yun , Hasan Aisha , Guerreiro Manuel , O'Reilly Richard J. 
Published: November 2019

Abstract
Latent CMV infection is controlled by a limited repertoire of immunodominant T-cells specific for viral peptides, particularly CMVpp65 and CMV IE-1. The antigen-specific T-cell subsets responsible for maintaining memory T-cells in this repertoire and repopulating them in response to periodic viral reactivations remain unclear. In this study, we generated T-cells specific for CMVpp65 from naïve (TN), TSCM, TCM and TEM subsets isolated from the blood of HLA-A*0201 normal seropositive donors and then comparatively characterized NLV-HLA-A*0201 Tetramer+ T-cells from each of these subsets. Following in vitro sensitization with artificial antigen-presenting cells transduced to express HLA-A*0201 and CMVpp65 and expansion with IL-7, IL-15 and IL-2, Tet+ T-cells were regularly generated from CD62L+CD45RO-CD95- TN and from CD62L+CD45RO-CD95+ TSCM, as well as TCM and TEM. Isolated Tet+ TN, TSCM, TCM and TEM were each able to generate IFN-γ, TNF-α and granzyme B. Each Tet+ subset also expressed similar level of PD-1 and KLRG-1. However, Tet+ TN and TSCM expressed higher levels of CD27 and lower levels of CD57 than TCM or TEM. Tet+ TSCM were distinguished from Tet+ TN, TCM and TEM by a significantly greater level of proliferation and by their rapid and selective expansion of NLV-specific T-cells bearing TCRs identical by amino acid sequences to those expressed by TEM and TCM in the blood. Thus, Tet+ TSCM rather than Tet+ TN constitute the principal repertoire for repopulation of immunodominant memory T-cells sustained in the circulation.

Disclosures
Hasan: Atara: Patents & Royalties.
A Comparison of Efficacy Following Two Different Doses of Granulocyte Colony Stimulating Factor (G-CSF) Alone for Mobilization of Peripheral Blood Stem Cells in 221 Multiple Myeloma Patients
Authors: Osmani Soufi , Brahimi Mohamed , Talhi Souad , Amani Kamila , Ouldjeriouat Hafida , Bouchama Samira , Charef Leila , Mazari Mohamed Amine , Entasoltan Badra , Yafour Nabil , Krim Amina , Bouhass Rachid Amar , Arabi Abdessamed , Bekadja Mohamed Amine 
Published: November 2019

Abstract
Introduction:
Intensive chemotherapy followed by autologous stem cell transplantation (ASCT) is currently the treatment of choice in multiple myeloma (MM). Mobilization of hematopoietic stem cell blood (HSCs) can be achieved either by the combination of chemotherapy plus growth factors or by growth factors alone. However, there is no consensus concerning the dose of growth factor alone that should be administered, with ranges varying from 5 microgr to 16 microgr/kg body weight.
In this context, we report our experience in mobilization of HSCs using growth factor alone at the dose between 15 microgr /kg and 10 microgr /kg in MM.
Patients and methods:
A total of 340 ASCT were performed in our center, from May 2009 until June the 31st 2016. These concerned 221 patients with MM. Patients were hospitalized at day -5 on which mobilization started with G-CSF alone (filgrastim) at the dose of 15 microgr /kg/daily subcutaneously for 5 days from May 2009 to October 2012 and at the dose of 10 microgr /kg from November 2012 to June 2016. The white blood cell count was assessed daily. Apheresis was performed at day -2 and day -1 using a Spectra Optia CMN device, and the CD34+ count was assessed by flow cytometry. A single leukapheresis was performed if the number of CD34+ cells was above 2.106/kg. Failure of mobilization was defined as a level of CD34+ less than 2.106/kg, after two leukapheresis.
In our study patients were divided into two groups: Group1 (G-CSF=15 microgr /kg) and Group 2 (G-CSF=10 microgr /kg) and the number of CD34+ were divided into three groups: optimal (³5.0 x 106 CD34+ cells/kg), suboptimal (2.0Ð5.0 x 106 CD34+ cells/kg) and poor (<2.0 x 106 CD34+ cells/kg) mobilization. Intensification was done using melphalan 200 mg/m2 on day -1.
Results:
Patient's characteristics are shown in Table 1. No significant difference was observed between the 2 groups. In this study, we found no significant difference in terms of optimal (p= 0.73), sub-optimal (p= 0.19) or poor (p= 0.11) harvest of stem cells between the 2 groups (table 2). Among the poor mobilizators with G-CSF, only 4 of them had a level of CD34+ harvest less than 0.5 x 106/kg. These patients did not receive an ASCT. 1,3% (4) of all apheresis failed to achieve acceptable harvest level.
Conclusion:
Our study showed that the mobilization regimen with G-CSF alone at the doses of 10 microgr/kg have the same efficacy as the doses of 15 microgr/kg and is interesting alternative to chemotherapy and G-CSF in patients with MM because it can be administered as an outpatient and is not associated with the risk of febrile neutropenia.

Disclosures
No relevant conflicts of interest to declare.
Safety and Efficacy of Donor-Derived Virus Specific Cytotoxic T Lymphocytes(CTL) Administered in Treatment for CMV/EBV Infections after Allogenetic Stem Cell Transplantation
Authors: Wang Jingbo , Huang Xiaojun , Hu Ying , Xue Song , Cheng Haoyu , Yin Yuming , Zhang Weijie , Gu Jiangying , He Junbao , Yang Fan 
Published: November 2019

Abstract
Objective:
To investigate the safety and efficacy of donor-derived cytomegalovirus(CMV) specific cytotoxic T lymphocytes(CTL) and Epstein-Barr virus(EBV) specific cytotoxic T lymphocytes(CTL) as immune therapy in CMV viremia and EBV viremia postallogeneic transplant.
Methods:
A total of fifty-three patients receiving haplo-identical allogeneic HSCT for hematological malignancy were eligible for recruitment to the study from February 2013 to December 2015. Thirty-eitht patients of CMV viremia postallogeneic transplant received CMV CTL. Fifteen patients of EBV viremia postallogeneic transplant received EBV CTL. The criteria for inclusion were: (1) plasma CMV/EBV DNA >1×103/ml. (2) Antiviral therapy (ganciclovir and foscaret) was not effective.(3) Antiviral therapy was not tolerated for pancytopenia. The criteria for exclusion were: (1) plasma CMV/EBV DNA <1×103/ml. (2) Prophylactically administered CMV-specific T cells and EBV-specific T cell. T-cell infusion: Patients were infused with a single dose of 2-3×105/kg weekly. Median number of infusion was 8(2-15). Criterion of therapeutical effect: Virus DNA copy number decreased by a log rank or above (Valid). Virus DNA copy number to zero(negative). Virus DNA copy number increased or not reduced ( Invalid).
Results:
38 cases of CMV viremia were effective in 28 cases, the effective rate was (73.7±7.1)%, the median onset time was 5 days (2-10). Plasma CMV was negative in 28 cases, the negative rate was (73.7±7.1)%, the median negative time was 11 days (2-24). 15 cases of EBV viremia were effective in 13 cases, the effective rate was (86.7±8.8)%, the median onset time was 5 days (2-11). Plasma EBV was negative in 13 cases, the negative rate was (86.7±8.8)%, the median negative time was 10 days (3-24). Adverse events: fever(n=1), skin rash(n=3), hypoxemia(n=2), diarrhea (n=1 uncertain), Tachycardia of sinus( n=1)
Conclusion:
Safety and efficacy of virus specific cytotoxic T lymphocytes(CTL) administered postallogenetic HSCT are exact. CTL can be used as second-line therapy of viral infections postallogenetic HSCT.

Disclosures
No relevant conflicts of interest to declare.
Impact of Muscle Mass, Evaluated By Ultrasound, and Muscle Strength in the Engraftment of Hematopoietic Stem Cell Transplantation(HSCT)
Authors: Pereira Andrea Z , Barban Juliana B S , Cocco Marister N , Pitito Bianca A , Hamerschlak Nelson 
Published: November 2019

Abstract
Introduction: In the HSCT, msucle mass and visceral fat are associated to comorbidities, mortality, length of stay, duration of use of immunosupressive drugs, the development of graft-versus host disease(GVHD) and survival. A recent study in patients undergone allogenic HSCT showed an inverse association between areas of visceral and peripherical fat with disease-free interval. In allogenic HSCT, decreased muscle mass is associated to higher prevalence of chronic GVHD and low performance. Objectives: To evaluate the muscle thickness(MT), visceral fat(VF) and muscle stregth(MS), correlating them with engraftment(EN). Methods: We studied 14 HSCT patients, adults(>=18 years), from Hospital Israelita Albert Einstein, Sao Paulo, Brazil. In the first day of hospitalization, before HSCT, we evaluated MT of right femoral quadriceps, 6 cm from the top edge of the patela; VF was measured in the abdominal area, and was characterized by the distance between the linea alba and the anterior wall of aorta artery. This measuments were evaluated by ultrasound in B-mode. In addition, all patients had their dominant upper limb strength evaluated by hand grip. Results: Most patients were women (57%) and the mean age was 50 years(+-16 years). We had haploidentical(57%), autologus(36%) and allogenic(7%). Most of our patients were overweight, mean 27 kg/m2(+-4 kg/m2). The EN average time was 16 days (+-6days). MT mean was 1,5 cm(+-0,3cm), VF 5,3 cm(+-1,4 cm) and MS 31 kgf(+-7,0 kgf). There was a negative and significant correlation between EN and MT(rs-0,8,p<0,05). We didn`t find any correlation with VF, MS and EN. Conclusion: The MT evaluated by ultrasound showed a strong correlation with EN. The ultrasound is pratical, low cost, no risk inHSCT, it could be more used for these patients.

Disclosures
No relevant conflicts of interest to declare.
Establishment of a Xenotransplantation Acute Myeloid Leukemia Model Using By Zebrafish
Authors: Ye Yongbin , Xu Xiaojun , Liu Qifa 
Published: November 2019

Abstract
Objecitve: To investigate the feasibility ofxenotransplant leukemia model using by zebrafish, and lay the foundation for the study of acute myeloid leukemia and the screening of the drugs for targeting therapy of acute myeloid leukemia.
Methods: Acute myeloid leukemia cell line KG1a was labeled with red fluorescent dye-MitoRed, then, the labeled cells was injected into the yolk sac of zebrafish embryos. Morphology observation, cell counting and histopathological detection were used to analysis the infiltration and metastasis of KG-1a cells in zebrafish.
Results: KG1a cells could proliferate and gradually spread to the entire abdominal cavity of the zebrafish After KG1a cells were injected into the yolk sac during 1-7 dpi, the results of cell counting in vitro also proved a signification proliferation of KG1a cells in zebrafish, suggesting that the implanted leukemia stem cells could survive, proliferate and spread in zebrafish. Further study detected the implanted cells could transfered to the liver of zebrafish, these cells showed the signature of KG1a cells by hematoxy -lin -eosin(HE) staining.
Conclusions: Human acute myeloid leukemia cells KG1a could survive, proliferate and migrate in zebrafish, suggesting xenotransplant leukemia model using by zebrafish is feasible. This model may provide benefit for the study of acute myeloid leukemia and the screening of the drugs for targeting therapy of acute myeloid leukemia.

Disclosures
No relevant conflicts of interest to declare.
Decreased Expression of PPARγ mRNA in Patients Correlates with aGVHD after Allo-HSCT
Authors: Wu Xiaojin , Zhang Jubin , Ma Shoubao , Ji Yuhan , Liu Shuangzhu , Bao Xiebing , Chen Jia , Wu Depei 
Published: November 2019

Abstract
Background and objective: Peroxisome proliferator-activated receptor (PPAR)-gamma(γ) is a member of superfamily of nuclear hormone receptors and involved in the lipids metabolism, adipocyte differentiation, atherosclerosis and anti-inflammation. The role of PPARγ in acute graft versus host disease (aGVHD ) remains unclear. In this study, we aimed to investigate the role of PPARγ during aGVHD after allogenic hematopoietic stem cell transplantation (allo-HSCT ).
Methods: 50 patients undering allo-HSCT and 20 healthy controls were enrolled in study. Peripheral blood (PB) of patients 30 days, 60 days, and 90 days were collected after allo-HSCT. We also collected PB samples at aGVHD onset and after aGVHD remission. Peripheral blood mononuclear cells (PBMCs) were isolated for real-time PCR to detect the mRNA expression of PPARγ, IFNγ, IL4, T-bet, GATA3, Foxp3, RORγt .
Results: Expression of PPARγmRNA in healthy controls were significant lower than that in patients after allo-HSCT(P<0.05). At the onset of aGVHD, the expression of PPARγmRNA was significantly lower than that in non-GVHD and increased when remission (P<0.05). PPARγexpression in severe aGVHD (grade 3 to 4) was lower than mild aGVHD (grade 1 to 2) patients (P<0.05). Gender, age, graft type, and the kind of disease showed no significant difference in the aGVHD and non-GVHD patients. The expression of IFNγ and T-bet increased after aGVHD and were negatively correlated with PPARγmRNA expression.
Conclusion: Our findings suggest that low expression of PPARγ is associated with aGVHD occurrence. PPARγ may be a useful indicator to predict aGVHD and follow-up.

Disclosures
No relevant conflicts of interest to declare.
Expandation of CD56-Bright NK Cell in Patients with Steroid-Refractory Graft-Versus-Host Disease Treated with Basiliximab and Etanercept
Authors: Sheng Lixia , Huang He , Tan Yamin , Luo Yi , Hu Yongxian , Fu Huarui , Shi Jimin 
Published: November 2019

Abstract
Objectives: Steroid-resistant aGVHD(SR-aGVHD) is a complication with high incidence of mortality following allogeneic stem cell transplantation. Our previous study has showed combined treatment by basiliximab and etanercept achieved high response in SR-aGVHD. The aim of this study is to investigate the changes of lymphocyte subsets in SR-aGVHD following treatment with basiliximab and etanercept.
Methods: We treated 11 SR-aGVHD patients with basiliximab 20mg on days 1, 4, 8, 15, and etanercept 25 mg twice a week for 4 weeks, followed by once weekly for 4 more weeks. Their peripheral blood lymphocyte subsets were assessed by flow cytometry before and after treatment.
Results: The overall response to treatment was 100% (11/11) with 72.7% (8/11) achieving a complete response. As expected, we found a significant depletion of both CD4+ and CD8+ T-cell subset at 4w following treatment. Conversely, the proportion of CD3-CD56+NK expanded significantly, accounting for 26.82±7.69% of PB lymphocytes at 6w following treatment, compared with 10.90±3.94% before treating. The increasement in NK proportion lasting from several weeks to several months. Moreover, the percentage of CD56bright and IFN-gamma-producing NK cell subsets also increased after combined treatments.
Conclusion: Expansion of CD56(bright) and IFN-gamma production NK cell subsets and contraction of CD4(+) and CD8(+) T cell numbers may contribute to the well control of SRaGVHD by basiliximab and etanercept. This finding provides supporting evidence for NK cell-mediated negative immunoregulation of activated T cells during aGVHD.

Disclosures
No relevant conflicts of interest to declare.
Improved Survival of High Risk Patients with Parainfluenza Virus Following Hematopoietic Cell Transplantation: Role of Aerosolized Ribavirin
Authors: Nguyen Isabelle T , Shashidhar Sumana , Brown Janice (Wes) M. 
Published: November 2019

Abstract
Parainfluenza viruses (PIV) ARE associated with severe respiratory tract infections among immunocompromised patients. However, the most perplexing feature of PIV following hematopoietic cell transplantation (HCT) is the dichotomous nature of risk for life-threatening infection. Specifically, the vast majority of patients will not require treatment of any kind whereas a small subset appears to be at such high risk of death that it has been questioned if successful treatment is even possible.
In 2007, we implemented a standardized approach to patients diagnosed with Parainfluenza virus (PIV) following HCT at Stanford University Medical Center (Fig 1) based on the need for supplemental oxygen and/or specific risk factors. We performed both a prospective analysis of cases of lower respiratory tract infection and a retrospective review of all 2495 patients transplanted during this period. The epidemiology, risk factors, clinical status, and outcome of the 115 PIV patients using this protocol from September 2007 through May 2015 shows that prudent, risk-stratified application of antiviral therapies in can result higher survival rates among patients with PIV post-HCT. Moreover, high risk patients who received aerosolized ribavirin had a lower mortality rate than those who were either not treated or received oral ribavirin.

Disclosures
No relevant conflicts of interest to declare.