Deferasirox Reduces Serum TNF-α but Impairs Renal Function in Patients with Thalassemia Major after 12 Months of Therapy

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3888-3888 ◽  
Author(s):  
Ersi Voskaridou ◽  
Eleni Plata ◽  
Dimitrios Christoulas ◽  
Charoula Xirakia ◽  
Eleni Stoupa ◽  
...  
Keyword(s):  
Renal Function ◽  
Serum Creatinine ◽  
Inflammatory Cytokines ◽  
Cystatin C ◽  
Serum Levels ◽  
Thalassemia Major ◽  
P Value ◽  
Tnf Α ◽  
Baseline Values ◽  
Tgf Β1

Abstract Deferasirox is an oral iron chelator approved for the management of iron overload in thalassemia major (TM). However, there are some concerns for its effect on renal function. Cystatin C (Cys-C) is a cysteine protease inhibitor, which is considered as a sensitive marker of GFR. Inflammation process has been recently implicated in TM pathophysiology. The aim of this study was to evaluate the effect of deferasirox on renal function and inflammatory cytokines in 52 TM patients. Deferasirox was administered at a dose between 10–30 mg/kg/day for a 12-month period. Serum Cys-C, serum creatinine (Cr), clearance of Cr (Ccr), albuminuria and inflammatory cytokines including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), IL-1α, IL-1β, IL-4, IL-10 and transforming growth factor (TGF)-β1 and β2, were measured at baseline and then after 6 and 12 months post-deferasirox therapy. Standard hematology and biochemistry was evaluated monthly. Serum Cys-C was measured using a latex particle-enhanced nephelometric immunoassay (Dade Behring, Liederbach, Germany). Serum levels of the above cytokines were determined using ELISA (R&D Systems, Minneapolis, MN, USA, for ILs, and Diaclone, Bensancon, France for TNF-α, TGF-β1 and TGF-β2). Ten healthy blood donors were also evaluated as control group. At baseline, TM patients had elevated values of Cys-C (p<0.0001) compared with controls. Specifically, 21/52 patients (40%) had higher Cys-C values than the upper normal limit according to manufacturer (0.95 mg/L), while no patient had increased levels of serum Cr (>1.4 mg/dl) and only 6 (11.5%) had low Ccr (<80 ml/min). Before deferasirox administration, TM patients had also increased levels of IL-6 (p=0.008), IL-1α (p=0.015), TGF-β2 (p=0.017), IL-10 (0.021), IL-4 (p=0.039), and a borderline increase of TNF-α (p=0.05) compared with controls (Table). Serum levels of Cys-C correlated strongly with Cr (r=0.657, p<0.0001), and Ccr (r=−0.625, p<0.0001) but also with IL-6 (r=0.441, r<0.001) and proteinuria (r=0.261, p=0.037). Il-1a correlated with Hb (r=−0.417, p<0.001) and IL-4 (r=0.474, p<0.001), while IL-6 correlated with TNF-α (r=0.37, p<0.01). After 6 and 12 months of therapy, deferasirox produced a dramatic reduction of ferritin, SGOT and SGPT compared with baseline values (p<0.0001), but concomitantly we observed an increase of Cys-C and Ccr during the same period (p<0.0001). In particular at the end of the study 32/52 patients (61.5%) had increased Cys-C values, while 10 (19.2%) had low Ccr and only one high serum Cr. Interestingly serum levels of TNF-α reduced post-deferasirox administration (p=0.01), while the levels of all other cytokines remained unchanged during therapy (Table). Our study suggests that deferasirox is an effective chelator in TM. However, its effect on renal function is not insignificant and needs further investigation. Inflammatory cytokines seem to have a role in the pathogenesis of TM but further studies are needed to fully elucidate this role as well as the effect of deferasirox, if any, on inflammation. Table 1. Characteristics of patients & controls (mean values ± SD) Parameters Controls (n=10) Patients-baseline values (n=52) p-value (patients vs. controls) Patients-12-month values p-value patients (baseline vs. 12 m) Age(years) 40.8±11.7 39.5±10.9 0.782 Gender(Male/Female) 4/6 22/30 0.346 Hb(g/dL) 14.8±2.6 8.8±1.4 <0.0001 8.7±1.5 AST(U/L) 29.3±10.1 46.7±23.9 <0.0001 35.5±19.2 <0.0001 ALT(U/L) 23.8±12.5 50.7±28.6 <0.0001 34.3±22.1 <0.0001 Ferritin(μg/L) 88±34.2 2355±1380 <0.0001 1516±1320 <0.0001 Serum Creatinine (mg/dL) 0.8±0.1 0.7±0.1 0.823 0.8±0.2 0.001 Creatinine Clearance (ml/min/1.732) 125.2±22.7 126.5±29.9 0.227 117.0±31.1 0.005 Proteinuria(mg/24h) 55.4±28.2 322.9±461.6 <0.0001 323.4±417.0 0.976 Cystatin-C (mg/L) 0.76±0.11 0.93±0.26 <0.0001 1.12±0.37 <0.0001 Inflammatory Cytokines IL-1α (pg/mL) 0.08±0.19 0.65±0.80 0.015 1.06±1.13 0.114 IL-1β (pg/mL) 2.30±2.54 1.68±2.37 0.475 2.05±2.82 0.571 IL-4 (pg/mL) ND 0.78±1.83 0.039 0.28±0.59 0.167 IL-6 (pg/mL) 0.09±0.21 2.50±4.42 0.008 3.00±7.51 0.752 TNF-α (pg/mL) 1.13±2.05 3.85±7.48 0.05 0.46±1.40 0.015 TGF-β1 (ng/mL) 87.1±21.7 107.5±53.6 0.180 112.1±74.0 0.678 TGF-β2 (pg/mL) 5.62±10.5 19.5±26.4 0.017 15.8±29.7 0.318

Stable Cystatin C Serum Levels Confirm Normal Renal Function in Patients With Dronedarone-Associated Increase in Serum Creatinine

2012 ◽  
Vol 18 (2) ◽  
pp. 109-112 ◽  
Author(s):  
David Duncker ◽  
Hanno Oswald ◽  
Ajmal Gardiwal ◽  
Ulrich Lüsebrink ◽  
Thorben König ◽  
...  
Keyword(s):  
Renal Function ◽  
Serum Creatinine ◽  
Cystatin C ◽  
Normal Renal Function ◽  
Serum Levels

Abstract P306: Inflammatory Biomarkers Participate in Physiopathology of Hypertensive Crisis

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Jose F Vilela-Martin ◽  
Days Oliveira-Andrade ◽  
Luciana N Cosenso-Martin ◽  
Michele L Gregorio ◽  
Moacir F Godoy ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Metabolic Profile ◽  
Inflammatory Process ◽  
Hypertensive Crisis ◽  
Serum Levels ◽  
P Value ◽  
Hypertensive Urgency ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Underlying Inflammation

Background: Recent evidence suggests the existence of an underlying inflammation process to vascular disease associated with chronic high blood pressure (BP), playing an important role in the pathophysiology of hypertension (HT). However, few studies show the participation of the inflammatory process in the pathophysiology of acute BP elevation. Objectives: To identify clinical and metabolic profile of presentation of hypertensive crisis (HC) divided into hypertensive urgency (HUrg) and emergency (HEmerg); 2 - To assess the involvement of inflammatory cytokines: IL-1β, IL-6, IL-8, IL-18, TNF-α and anti-inflammatory IL-10 in subjects with HC. Methods: We studied 274 individuals: 74 normotensive (NT), 74 controlled hypertensive (CHT), 50 HUrg and 78 HEmerg. Serum levels of cytokines were made by MULTIPLEX and ELISA techniques. Analysis of variance was used to compare the groups, with significant p-value <0.05. Results: The diastolic BP and heart rate were greater in the HC group (120mmHg and 85bpm, respectively) compared to the CHT group (75mmHg and 68 bpm, respectively; p<0.05). Individuals with HEmerg were older. Glycaemia was significantly higher in the HEmerg group (113mg/dL) in comparison to NT and CHT (91mg/dL and 98mg/dL, respectively; p<0.05). HDL-c was significantly lower in HEmerg group compared to the NT group (p=0.0088). Potassium levels were lower in HEmerg group compared to the other groups NT, CHT and HUrg (p=0.0118, p=0.036 and p=0.036; respectively). All measured cytokines were significantly greater in subjects who had HC compared to NT and CHT groups. Logistic regression showed that IL-1β, IL-6, IL-8 and IL-18 were predictors for HC development with odds ratios of: 4.29 (2.01 - 9.19), 11.02 (3.98 - 30.45), 22.56 (7.99 - 63.64) and 3.85 (1.85 - 8.02), respectively. Conclusions: The levels of inflammatory cytokines (IL-1β, IL-6, IL-8 and IL-18) and anti-inflammatory (IL-10) are higher in HUrg and HEmerg groups compared to NT and CHT groups. This suggests the involvement of inflammatory cytokines in the pathogenesis of acute hypertensive event.

scholarly journals Liver resection promotes (regulates) pro-inflammatory cytokines in patients with hepatocellular carcinoma

2021 ◽  
Author(s):  
Farshid Fathi ◽  
Behnam Sanei ◽  
Mazdak Ganjalikhani Hakemi ◽  
Reza F. Saidi ◽  
Abbass Rezaei
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Resection ◽  
Liver Regeneration ◽  
Inflammatory Cytokines ◽  
Animal Studies ◽  
Transforming Growth Factor ◽  
Serum Levels ◽  
Tnf Α ◽  
Before And After ◽  
Tgf Β1

Abstract Objective: Several animal studies have shown the roles of cytokines in regulating liver regeneration following liver resection (LR), which is a type of surgery is designed to remove cancerous tumors from liver. This study investigated how the expressions and serum levels of some pro- and anti-inflammatory cytokines in patients with hepatocellular carcinoma (HCC) were changed during LR.Liver tissues from 15 patients with HCC were collected and the levels of interleukin-6 (IL-6), tumornecrosis factor-alpha (TNF-α), IL-1α, IL-1 β, IL-10, and transforming growth factor- beta1 (TGF-β1) were assessed using real-time PCR assay at different times before and after LR. The serum values of TNF-α and IL-6 were also measured by ELISA.Results: After 60 and 90 minutes of LR, IL-6 gene expression was significantly increased (P < 0.001-0.05). The same trend was also observed in TNF-α expression after 90 minutes of LR (P <0.01). No significant changes were observed in the expressions of IL-1α, IL-1β, IL-10, and TGF-β1 before and after LR. In addition, LR had significant effects on TNF-α and IL-6 serum levels (P<0.05-0.0001). Our data provided further evidence to reveal that IL-6 and TNF-α cytokines are critical to improve liver regeneration.

scholarly journals Changes in Urinary and Serum Levels of Novel Biomarkers after Administration of Gadolinium-based Contrast Agents

2016 ◽  
Vol 11 ◽  
pp. BMI.S39199 ◽  
Author(s):  
Habib Mawad ◽  
Louis-Philippe Laurin ◽  
Jean-François Naud ◽  
François A. Leblond ◽  
Nathalie Henley ◽  
...  
Keyword(s):  
Renal Function ◽  
Contrast Agents ◽  
Cystatin C ◽  
Normal Renal Function ◽  
Serum Levels ◽  
Serum Cystatin C ◽  
Baseline Serum ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Novel Biomarkers ◽  
Neutrophil Gelatinase

Objective The aim of our study is to describe the changes in urinary and serum levels of novel biomarkers after gadolinium contrast administration in patients with normal renal function. Methods We measured four biomarkers in 28 volunteers: interleukin-18 (IL-18), N-acetyl-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin, and cystatin C. Urinary and serum samples were collected at 0, 3, and 24 hours following gadolinium administration. Results Baseline serum creatinine was 57.8 ± 34.5 μmol/L and remained stable. Urinary IL-18 levels increased significantly at three hours (10.7 vs. 7.3 ng/mg creatinine; P < 0.05). Similarly, urinary NAG levels increased significantly at three hours (3.9 vs. 2.2 IU/mg creatinine; P < 0.001). For both these markers, the difference was no longer significant at 24 hours. No statistically significant differences were observed for urinary and serum neutrophil gelatinase-associated lipocalin levels and for serum cystatin C levels. Conclusions Urinary IL-18 and NAG levels increased transiently after administration of gadolinium-based contrast agents in patients with normal renal function.

scholarly journals Pro- and Anti-Inflammatory Cytokines in the First Trimester—Comparison of Missed Miscarriage and Normal Pregnancy

2021 ◽  
Vol 18 (16) ◽  
pp. 8538
Author(s):  
Maciej Kwiatek ◽  
Tomasz Gęca ◽  
Anna Kwaśniewska
Keyword(s):  
Immune Response ◽  
Inflammatory Cytokines ◽  
First Trimester ◽  
Normal Pregnancy ◽  
Control Group ◽  
Study Group ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Anti Inflammatory ◽  
Tgf Β1

The advantage in response of Th2 over Th1 is observed in normal pregnancy in peripheral blood. A disturbance of this balance can lead to symptoms of miscarriage and pregnancy loss. The aim of this study was to evaluate the pro- and anti-inflammatory cytokines in sera of women who were diagnosed with missed miscarriage in the first trimester and to compare this systemic immune response to the response in women with normal pregnancy. The study group consisted of 61 patients diagnosed with missed miscarriage. In total, 19 healthy women with uncomplicated first trimester created the control group. Cytokines were determined in the maternal serum by ELISA. The analysis included INF-γ, TNF-α, Il-1β, Il-4, Il-5, Il-6, Il-9, Il-10, Il-13 and TGF-β1. Th1 cytokine levels in the study group reached slightly higher values for INF-γ, Il-1β and slightly lower for IL-6 and TNF-α. In turn, Th2 cytokine levels in the study group were slightly higher (Il-9, Il-13), significantly higher (Il4, p = 0.015; Il-5, p = 0.0003) or showed no differences with the control group (Il-10). Slightly lower concentration involved only TGF-β1. Analysis of the correlation between levels of pro- and anti-inflammatory cytokines resulted in some discrepancies, without showing predominance of a specific immune response. The results did not confirm that women with missed miscarriage had an advantage in any type of immune response in comparison to women with normal pregnancy.

l-Carnitine-induced amelioration of HFD-induced hepatic dysfunction is accompanied by a reduction in hepatic TNF-α and TGF-β1

2018 ◽  
Vol 96 (6) ◽  
pp. 713-725 ◽  
Author(s):  
Mabrouk Attia Abd Eldaim ◽  
Fatma Mohamed Ibrahim ◽  
Saher Hassan Orabi ◽  
Azza Hassan ◽  
Hesham Saad El Sabagh
Keyword(s):  
Protein Expression ◽  
High Density Lipoprotein ◽  
Body Mass ◽  
Density Lipoprotein ◽  
Basal Diet ◽  
Serum Levels ◽  
High Density ◽  
Control Group ◽  
Tnf Α ◽  
Tgf Β1

In this study, we evaluated the possible mechanisms through which l-carnitine ameliorates the adverse effects from obesity in rats, induced with a high-fat diet (HFD). For this, 56 albino Wister rats were randomly assigned to 7 groups. The control group was fed a basal diet and injected with saline. The second group was fed the basal diet and injected with l-carnitine (200 mg/kg body mass, by intraperitoneal injection; i.p.). The third group were fed the HFD. The fourth group was fed the HFD and injected with l-carnitine (200 mg/kg body mass, i.p.) for 8 weeks. The fifth group was fed the HFD for 10 weeks. The sixth group were fed the HFD for 10 weeks and were also injected with l-carnitine (200 mg/kg body mass, i.p.) during the final 2 weeks. The seventh group was fed the HFD diet for 8 weeks then the basal diet for 2 weeks. The HFD induced significantly increased levels of hyperglycemia, lipid peroxidation, pathological changes, TNF-α and TGF-β1 protein expression in hepatic tissue, food intake, body weight gain, serum levels of total and non-high-density lipoprotein cholesterol, ketone bodies, triacylglycerol, urea, creatinine, AST, and ALT. However, the HFD diet significantly decreased serum levels of high-density lipoprotein (HDL) and hepatic levels of reduced glutathione. l-Carnitine ameliorated the effects of the HFD on the above-mentioned parameters. This study indicated that l-carnitine had protective and curative effects against HFD-induced hepatosteatosis by reducing hepatic oxidative stress and protein expression of TNF-α and TGF-β1.

The Possible Protective Effect of Selenium on Liver Dysfunction in a Rat Model of Extrahepatic Cholestasis

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Fatma M Lebda ◽  
Sahar M El Agaty ◽  
Noha A Nassef ◽  
Marina A Aziz
Keyword(s):  
Bile Duct ◽  
Transforming Growth Factor ◽  
Group Versus ◽  
Serum Levels ◽  
Selenium Supplementation ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Tgf Β1 ◽  
Necrosis Factor

Abstract Background Oxidative stress and inflammation are primarily implicated in the development and progression of liver injury during cholestasis. Selenium, a known essential antioxidant trace element, was found to provide a remarkable antioxidant and anti-inflammatory effects on various diseases. Aim This study was planned to evaluate the possible protective effect of selenium supplementation in a rat model of chronic cholestasis. Design Experimental study. Methods This study was carried out on adult male rats allocated randomly into sham, bile duct ligated (BDL), and BDL-selenium treated (BDL-Se) groups. Sodium selenite was given by gavage daily, in a dose of 100 µg/kg for 6 weeks, starting 2 weeks before the BDL. Results BDL group presented a significant increase in serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and liver levels of malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), and transforming growth factor beta 1(TGF-β1), associated with a significant decrease in serum levels of total proteins (TP) compared to sham group . Selenium supplementation significantly lowered serum levels of AST, ALT, ALP, and liver levels of MDA, TNF-α, and TGF-β1 along with a significant increase in serum TP in BDL-Se group versus BDL rats. Histological analysis of liver showed a significant attenuation of the inflammatory score and a significant decrease in the percentage area of collagen deposition in BDL-Se group versus BDL rats. Conclusion Selenium supplementation reduces liver injury and improves liver functions in experimental cholestasis probably by its antioxidant and anti-inflammatory activities, which further alleviate the liver fibrosis. Abbreviations BDL: bile duct ligated group, BDL-Se: bile duct ligated-selenium group, MDA: malondialdehyde, TNF-α: tumour necrosis factor-alpha, TGF-β1: transforming growth factor- beta1, ROS: reactive oxygen species, mRNA: messenger RNA, IL-6: interleukin-6, BW: body weight, AST: aspartate aminotransferase, ALT: alanine aminotransferase, ALP: alkaline phosphatase, TP: total proteins, CCl4: carbon tetrachloride, GPx: glutathione peroxidase enzyme, SOD: superoxide dismutase, IL-1: interleukin-1.

scholarly journals Measurement of renal function in kidney donors using serum cystatin C and β2-microglobulin

2003 ◽  
Vol 40 (6) ◽  
pp. 656-658 ◽  
Author(s):  
George T John ◽  
Jude Joseph Fleming ◽  
Girish S Talaulikar ◽  
R Selvakumar ◽  
Paaulose P Thomas ◽  
...  
Keyword(s):  
Renal Function ◽  
Serum Creatinine ◽  
Cystatin C ◽  
Critical Value ◽  
Critical Values ◽  
Published Data ◽  
Serum Cystatin C ◽  
Serum Cystatin ◽  
Kidney Donors ◽  
Reduced Renal Function

Background: The usefulness of serum cystatin C and serum β2-microglobulin (B2M) as markers of glomerular filtration rate (GFR) were compared in kidney donors before and after nephrectomy. Methods: Blood samples were taken from 28 donors (15 women and 13 men) for serum creatinine, urea, cystatin C and B2M estimation a median of 7 days before and 10 days after nephrectomy. Results: Estimated GFR decreased from a median of 86.2 mL/min/1.73 m2 to 60.3 mL/min/1.73 m2, a median decrease of 28.6%. Serum creatinine increased by 40% and urea by 30.4%; serum cystatin C increased by 31.2% and serum B2M increased by 65.6%. Using published data on biological variation, critical values were calculated. An increase in serum creatinine above 18 µmol/L detected the decline in renal function in 26/28 (92.9%) subjects. Increases in serum B2M greater than a critical value of 0.94 mg/L detected 24/28 (85.7%) of these subjects, but the critical value of 0.59 mg/L for cystatin C detected only 8/28 (28.6%). Conclusion: Using critical values, serial measurement of serum creatinine was better than serum B2M in detecting reduced renal function. Because of its large intraindividual variation, serial serum cystatin C estimation was very poor in detecting reduced renal function.

Interleukin-6, Hepcidin, and Other Biomarkers in Anemia of Chronic Disease (ACD) and Chemotherapy-Induced Anemia (CIA): Potential Therapeutic Targets.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2086-2086 ◽  
Author(s):  
Saroj Vadhan-Raj ◽  
Xiao Zhou ◽  
Carlos E. Bueso-Ramos ◽  
Shreyaskumar Patel ◽  
Robert S Benjamin ◽  
...  
Keyword(s):  
Chronic Disease ◽  
Inflammatory Cytokines ◽  
Linear Regression Analysis ◽  
Transferrin Saturation ◽  
Serum Levels ◽  
Serum Samples ◽  
Anemia Of Chronic Disease ◽  
Baseline Serum ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

Abstract Abstract 2086 Background: Anemia in patients with malignancies can be multifactorial including anemia of chronic disease (ACD), also known as anemia of inflammation (AI), and chemotherapy (CT)-induced anemia (CIA) from myelosuppression. Although, exact mechanism for ACD is not known, induction of hepcidin, a key iron-regulatory hormone, by Interleukin (IL)-6 and other pro-inflammatory cytokines with resulting hypoferremia and limitation of iron supply to the bone marrow appear to be major contributors to pathogenesis of anemia. Hepcidin reduces iron levels by inducing degradation of the cellular iron exporter, ferroportin. The objective of this study was to examine the levels of various cytokines/regulators that may play role in ACD. Methods: Chemo-naïve patients with sarcoma scheduled to initiate first-line doxorubicin-based chemotherapy had blood samples drawn at baseline, and following chemotherapy (post cycles1, 3 and 6) for analysis of pro-inflammatory cytokines/other biomarkers of anemia. Serum samples were analyzed for IL-1β, IL-6, TNF-α, Hepcidin, hemojuvelin, ferroportin, soluble transferrin receptor (sTFR), and C-reactive protein (CRP) using ELISA techniques (R&D Diagnostics, Uscn Life Science Inc, or Abnova). Correlations between these biomarkers and Hgb levels at baseline and during the study period were calculated by linear regression analysis (SAS 9.2). Results: Of the 49 patients enrolled on to the clinical trial, there were 26 (53%) women and 23 (47%) men, with median age 45 years (range 19–65 years). Twenty-five percent of the patients had Hgb less than 12g/dL (range, 8.9–15.9 g/dL) prior to CT. At baseline, 50% of the pts had hypoferremia with low serum iron and transferrin saturation <20%. Baseline serum levels of IL-6 (r= −0.73, p<0.0001), hepcidin (r= −0.46, p=0.005), CRP (r= −0.46, p=0.003), sTFR (r= −0.32, p=0.064) inversely correlated with hemoglobin levels prior to CT, supporting their role in ACD. During CT (median 4, range; 1–6 cycles), Hgb declined in all pts with 55% requiring PRBC transfusions (77% of pts starting with baseline Hgb < 12 g/dL vs 47% of pts with baseline Hgb > 12 g/dL). Interestingly, as shown below, Hepcidin, IL-6, and sTFR all significantly negatively correlated with Hgb levels during CT. No significant correlation was found for IL-1β, TNF-α, ferroportin, or hemojuvelin levels with Hgb. Conclusions: IL-6 and Hepcidin pathway appears to play an important role in anemia in cancer patients before and during CT. Treatment with novel agents targeting this pathway may provide effective strategies for prevention and treatment of ACD and CIA. Disclosures: Vadhan-Raj: JNJ: Research Funding.

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