Pretransplant C-reactive Protein Research Articles

Impact of Pretransplant C-Reactive Protein, Neutrophiles, Platelets, and Albumin Levels on Recipient Survival After Simultaneous Pancreas and Kidney Transplantation

BackgroundLong-lasting diabetes mellitus type 1 and end-stage renal disease induce severe metabolic and immunological deterioration. Pretransplant C-reactive protein (CRP) and albumin (ALB) levels have impact on kidney transplantation. We evaluated impact of preoperative CRP, ALB, neutrophiles (NEU) and platelets (PLT) count, on one- and five-year recipients survival after simultaneous pancreas and kidney transplantation (SPK). MethodsAmong 103 SPK recipients, parameters: CRP (mean: 4.5±4.97mg/L); NEU (mean: 5.12 ±2.13∗103/mm3); PLT (mean: 244±84∗103/mm3); ALB (mean 4.5±0.75 g/dL) were obtained before transplantation. Cox regression, uni-, multivariate analysis for one- and five-year survivals were performed with 95% Confidence Intervals (CI) and area under ROC curve (AUC) was assessed. ResultsIn Cox regression, ALB <3,65g/dL had significant impact for one-year and five-year survivors with hazard ratios: 8 (CI:1.5-38.28, p<0.05) and 3.13 (CI:1.45-6.73, p<0.05), respectively. In univariate analysis, we found significantly decreased one-year survival if: PLT<180∗103/mm3, ALB <3.65g/dL, NEU>5.8∗103/mm3 and CRP>2.25mg/L with odds ratios (OR): 6.75 (CI: 2.12-21.15); 4.05(CI:1.3-12.09); 2.97 (CI: 1.02-8.64) and 5.51 (CI:1.67-18.19), respectively. Independent factors for five-year survival were: CRP, ALB and PLT with OR: 4.72(CI:1.67–13.29); 3.31(CI:1.18–9.25) and 4.2(CI:1.39–12.68), respectively. In multivariate analysis, we built two models for one-year survival. Model 1 (ALB+PLT) with OR: 3.12 (CI:0.97-10.07) and 5.55 (CI:1.67-18.4); and model 2 (CRP+PLT) with OR: 5.51 (CI:1.5-17.3) and 4.3 (CI:1.2-15.06), respectively. AUC for models 1 and 2 were: 0.74 and 0.759, respectively. ConclusionsNEU, PLT, ALB and CRP levels assessed before transplantation are independent factors for one- and five-year SPK recipients survival.

A prospective observational study on the traditional and novel risk factors associated with post-transplant diabetes mellitus in renal transplant recipients

Introduction and Aim: Post Transplant Diabetes Mellitus (PTDM) constitutes a major co-morbidity that has significant impact on the patient and renal allograft outcome. Various traditional risk factors like dialysis vintage, immunosuppressive medication, viral infections have known to be associated with PTDM. Novel risk factors and its causative role in PTDM remains unexplored. The study looked at the incidence of PTDM at 6 months post renal transplantation and correlation of PTDM with known traditional and novel risk factors like pre-transplant C-reactive protein (CRP) level and Trace element deficiency.&#x0D; &#x0D; Material and Methods: 30 consecutive renal transplant recipients more than 18 years of age were inducted into the study. Demographic data, known pre-transplant and post-transplant risk factors associated with development of PTDM were collected. Pre-transplant CRP and serum Trace element (Aluminum, Copper, Selenium and Zinc) levels were estimated. PTDM was diagnosed by home based glucometer monitoring and confirmed by Oral glucose tolerance test (OGTT).&#x0D; &#x0D; Results: The incidence of PTDM was 36.6% at six months post renal transplant. Among the pre-transplant risk factors, higher age and positive family history of diabetes mellitus had a strong association with the occurrence of PTDM. Pre-transplant Zinc deficiency emerged as a significant novel risk factor for the development of PTDM.&#x0D; &#x0D; Conclusion: Apart from known traditional risk factors, novel risk factors are associated with development of PTDM.

Validation of Pre-Transplant Biomarker Measurement and Risk Score for Non-Relapse Mortality after Allogeneic Hematopoietic Cell Transplant (HCT)

Validation of Pre-Transplant Biomarker Measurement and Risk Score for Non-Relapse Mortality after Allogeneic Hematopoietic Cell Transplant (HCT)

Outcomes and risk factors identification in urgent lung transplantation: a multicentric study.

In rapidly lung deteriorating patients, urgent lung transplantation (ULT) seems the only definitive therapy. Few publications on this topic report conflicting results, putting a word of caution about ULT programs. A national ULT program was introduced in 2010: patients on mechanical support may be transplanted with the first available graft. We reviewed the experience of three national center, focusing on post-operative outcomes after ULT. Ten patients (17.5%) died awaiting transplantation, while 47 underwent LT with a median urgent waiting list time of 6 days. Pre-operatively, 4.3% of patients were supported only by mechanical ventilation (MV), 55.3% by extracorporeal membrane oxygenation (ECMO) and the remaining 40.4% by both. The main indication was cystic fibrosis (64%). Median recipient lung allocation score was 72. In-hospital mortality was 19%. MV and ECMO median duration of 7 and 3 days, respectively while intensive care unit (ICU) and hospital stay were 20 and 46 days, respectively. At long-term, 1- and 3-year survival rate were 74% and 70%, respectively. Highly impact risk factors for in-hospital mortality were both presence and duration of preoperative veno-arterial ECMO and pre-transplant C-reactive protein level. ULT program allows transplantation in a significant percentage of patients with acceptable results. Pre-operative recipient selection is mandatory to improve clinical outcomes.

C-reactive protein is an independent predictor for hepatocellular carcinoma recurrence after liver transplantation.

BackgroundSerum C-reactive protein (CRP) is a prognostic factor for overall survival (OS) and recurrence of hepatocellular carcinoma (HCC) in patients treated with resection or non-surgical treatment. Here, we investigated the association of elevated CRP (≥1 vs. <1 mg/dL) with (i) recurrence of HCC and (ii) OS after liver transplantation (LT).MethodsAdult HCC patients undergoing orthotopic deceased donor LT at the Medical University of Vienna between 1997 and 2014 were retrospectively analysed.ResultsAmong 216 patients included, 132 (61.1%) were transplanted within the Milan criteria and forty-two patients (19.4%) had microvascular invasion on explant histology. Seventy patients (32.4%) showed elevated CRP (≥ 1 mg/dL). On multivariate analysis, a CRP ≥ 1 mg/dL was an independent risk factor for HCC recurrence with a 5-year recurrence rate of 27.4% vs. 16.4% (HR 2.33; 95% CI 1.13–4.83; p = 0.022). OS was similar in patients with normal vs. elevated CRP levels.ConclusionsElevated serum CRP is associated with HCC recurrence after LT and may be a marker for more aggressive tumor biology. Future studies should evaluate whether patients with elevated pre-transplant CRP levels benefit from closer monitoring for HCC recurrence.

Pretransplant C-reactive protein as a prognostic marker in allogeneic stem cell transplantation: A PRISMA-compliant meta-analysis.

Background:Numerous reports have explored the prognostic value of pretransplant serum C-reactive protein (CRP) in patients receiving allogeneic stem cell transplant (ASCT), but the results remain conflicting. Therefore, we performed a meta-analysis to comprehensively assess the prognostic value of pretransplant serum CRP in patients receiving ASCT.Methods:We systematically searched eligible studies in PubMed, Embase, and Web of Science from 1999 to September 2018. The pooled hazard ratios (HRs) and their corresponding 95% CIs were used to synthetically assess the prognostic value of pre-ASCT CRP in terms of overall survival (OS), non-relapse mortality (NRM), and acute graft versus host disease (aGVHD).Results:A total of 14 articles with 15 studies containing 3458 patients were included in this meta-analysis. The pooled results showed that high pre-ASCT CRP level was significantly related to worse OS (HR = 1.63; 95% CI: 1.34–1.98; P < .05), to an increased risk of NRM (HR = 2.06; 95% CI: 1.62–2.62; P < .05), and aGVHD (HR = 1.35; 95% CI: 1.07–1.71; P < .05). Additionally, sensitivity and subgroup analyses demonstrated that our pooled results were stable and reliable.Conclusions:High pre-ASCT serum CRP was significantly associated with worse OS, as well as higher risk of NRM and aGVHD. CRP may be a candidate factor of updating the existing risk scoring systems or establishing a novel risk scoring systems, which has the potential of guiding patient selection for ASCT and proceeding with risk-adapted therapeutic strategies. However, more high-quality clinical studies and basic research are required to further validate our findings in view of several limitations in our meta-analysis.

Pretransplant C-reactive protein, ferritin, albumin, and platelet count as prognostic biomarkers of hematopoietic stem cell transplantation outcome in hematological malignancies

Aim To study the prediction of prognosis after hematopoietic stem cell transplantation (HSCT) by clinically available biomarkers prior to transplantation (CRP, Ferritin, albumin and platelet count). Background Previous studies have shown that a number of objective laboratory “biomarkers” are of interest in pre-HSCT risk-assessment: Serum albumin inversely correlates with age, smoking, obesity and hypertension, and predicts cardiovascular mortality. Serum ferritin is an acute phase reactant, and elevated levels suggest iron overload, which has been linked to post-HSCT infections. Finally low platelet count, could indicate poor marrow function related to persistent malignancy or effects of prior treatment. Methods The study included patients admitted at the Bone marrow transplantation Units in Egypt (Ain Shams University Hospitals and Maadi Armed Forces Medical Compound and Sheikh Zayed Specialized Hospital) between August 2015 and December 2016. The study population consisted of 30 adults aged from 18 to 60 years; 26 patients were subjected to autologous-HSCT to treat high-risk or relapsing NHL, MM, relapsing HL, and 4 patients subjected to allogeneic-HSCT to treat 1st complete remissiom (CR) AML, 2nd CR AML. The biomarkers included pre-transplant serum albumin, platelet count, C-reactive protein (CRP) and serum ferritin were centrally quantified by (ELISA) technique. All patients were followed up till day +90 post transplant. Results Shock developed post-transplant in patients with CRP ˃10 mg/L (P=0.026) while non-relapse mortality was associated with the pre-specified thresholds of platelet count Conclusion We conclude that elevated level of pre-transplant CRP, s.ferritin associated with high NRM without statistically significant difference while NRM was higher in patients with normal s.albumin pre-transplant without statistically significant difference, low platelet count

Elevated pre-transplant C-reactive protein identifies a high-risk subgroup in multiple myeloma patients undergoing delayed autologous stem cell transplantation.

The significance of elevated C-reactive protein (CRP) prior to autologous stem cell transplantation (ASCT) in multiple myeloma (MM) has not been studied. We analyzed 1111 MM patients who underwent ASCT at Mayo Clinic from 2007 to 2015. A total of 840 patients (76%) received early ASCT (⩽12 months from diagnosis) and 271 patients (24%) received delayed ASCT (>12 months from diagnosis). Elevated CRP (> upper normal limit (8 mg/L)) was seen in 14% and 22% of patients undergoing early and delayed ASCT, respectively (P=0.003). There was no correlation of CRP with pre-transplant response, bone marrow plasma cell percentage or labeling index. Patients with an elevated CRP had a higher likelihood of having circulating plasma cells prior to ASCT (33 vs 19%; P<0.001). In the early ASCT cohort, the median overall survival (OS) in patients with normal and elevated CRP was not reached and 91 months respectively (P=0.011). In the delayed ASCT cohort, the median OS in respective groups were 73 and 30 months respectively (P<0.001), with elevated CRP being an independent prognostic marker on multivariate analysis (hazard ratio 2.0; 95% confidence interval, 1.0-3.8; P=0.045). Elevated pre-transplant CRP identifies a high-risk population especially in patients undergoing delayed ASCT and should be incorporated in the pre-transplant evaluation.

Prognostic Impact of Pre-Transplant Serum C-Reactive Protein in Patients Receiving a Single-Unit Unrelated Cord Blood Transplantation

Background: C-reactive protein (CRP) is an acute-phase protein and its serum level rises in response to inflammation. There have been some reports about the relationship between the serum CRP level before allogeneic hematopoietic stem cell transplantation (HSCT) and transplant outcomes. This study particularly evaluated the impact of pre-transplant CRP on the outcome in patients who received a single-unit unrelated cord blood transplantation (UCBT) for hematologic malignancies.Patients and methods: Adult patients receiving UCBT as first HSCT for hematologic malignancies between April 2009 and April 2016 at Kanagawa Cancer Center were retrospectively analyzed in this study. Serum CRP was measured by a latex agglutination assay (normal range 0.0-0.3 mg /dl). The time of measurement was within a few days before the conditioning procedure. Patients were divided into 2 groups according to the serum CRP levels (normal CRP group [≤0.03 mg/dl] and high CRP group [> 0.03 mg/dl)]). A total of 80 patients (pts) included 36 pts with acute myeloid leukemia (AML), 27 pts with acute lymphoid leukemia (ALL), 13 pts with myelodysplastic syndrome (MDS), and 4 pts with others. The median age was 59 years (range, 20-68 years). There were 45 males and 35 females. A disease risk at transplantation indicated a standard risk in 47 pts and a high risk in 33 pts. Myeloablative conditioning (MAC) was employed for 25 pts and reduced intensity conditioning (RIC) was for 55 pts. Data were analyzed with EZR statistical software.Results: The median level of serum CRP at pre-transplant was 0.17 mg/dl (range: 0.01-12.93). No. of patients in normal and high CRP levels was 56 pts and 24 pts, respectively. Disease high risk was significantly associated with a high level of serum CRP. Other pre-transplant factors such as age, gender, diagnosis, comorbidity index, and serum ferritin levels were not related with serum CRP levels. The high incidence of gradeII-IVacute GVHD was significantly associated with high CRP group compared to normal CRP group (55% vs. 19%, p = 0.001). After a median follow-up of 16 months (range: 1-86 months), 3-year overall survival (OS) was 62%. The cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) at 3 years was 26% and 14%, respectively. According to univariate analysis, factors associated with worse 3-year OS included disease high risk at transplantation (vs. low risk; 49% vs. 70%, p = 0.025) and high CRP levels (vs. normal CRP levels; 28% vs. 77%, p < 0.001). Higher 3-year CIR was significantly correlated with high CRP levels (vs. normal CRP levels; 46% vs. 18%, P = 0.009). Adverse factors for NRM was high scores (≥3) of HCT-CI (vs. low scores (≤2) of HCT-CI; 25% vs. 5%, p=0.029). Multivariate analysis showed that high CRP levels (hazard ratio [HR], 4.13; 95% confidence interval [CI], 1.76-9.63; p = 0.001) was an independent determinant of 3-year OS. Prognostic factors related with CIR and NRM was high CRP levels (HR, 2.63; 95%CI, 0.96-7.21; p = 0.059) and high scores of HCT-CI (HR, 4.25; 95%CI, 0.89-20.29; p = 0.069) respectively, but those difference did not reach statistical significance.Conclusions: Pre-transplant serum CRP might be a useful biomarker for predicting the transplant outcome and the development of acute GVHD following UCBT. DisclosuresNo relevant conflicts of interest to declare.

Pretransplant Levels of CRP and Interleukin-6 Family Cytokines; Effects on Outcome after Allogeneic Stem Cell Transplantation.

Several pretransplant factors, including CRP (C-reactive protein) levels, reflect the risk of complications after allogeneic stem cell transplantation. IL-6 induces CRP increase, and we therefore investigated the effects of pretransplant IL-6, soluble IL-6 receptors, IL-6 family cytokines and CRP serum levels on outcome for 100 consecutive allotransplant recipients. All patients had related donors, none had active infections and 99 patients were in complete remission before conditioning. The incidence of acute graft versus host disease (aGVHD) requiring treatment was 40%, survival at Day +100 82%, and overall survival 48%. Despite a significant correlation between pretransplant CRP and IL-6 levels, only CRP levels significantly influenced transplant-related mortality (TRM). However, CRP did not influence overall survival (OS). Pretransplant IL-31 influenced late TRM. Finally, there was a significant association between pretransplant IL-6 and early postconditioning weight gain (i.e., fluid retention), and this fluid retention was a risk factor for aGVHD, TRM and OS. To conclude, pretransplant CRP, IL-31 and early posttransplant fluid retention were independent risk factors for TRM and survival after allotransplantation.

Post-Transplant C-Reactive Protein Predicts Arterial Stiffness and Graft Function in Renal Transplant Recipients

BackgroundThe aim of this study was to evaluate the renal and cardiovascular outcomes of post-transplant c-reactive protein (CRP) levels. MethodsOne hundred fifty renal transplant recipients (113 men; median age, 38.9 ± 10.8 years) were cross-sectionally analyzed. Mean pre-transplant and post-transplant CRP levels were analyzed by the 1st, 3rd, 6th, 12th, and 24th months of transplantation. Patients were divided into 3 groups according to mean post-transplantation CRP levels: group 1 (CRP >20 mg/L and fluctuating levels; n = 34), group 2 (CRP, 6–20 mg/L; n = 40), and group 3 (CRP <6 mg/L; n = 76). Arterial stiffness was measured by means of carotid femoral pulse-wave velocity (PWv) by use of the SphygmoCor system. ResultsPatients in group 1 had significantly lower estimated glomerular filtration rate (eGFR) (P = .000) and left ventricular systolic function and higher duration of dialysis before transplantation, pulse-wave velocity (PWv), proteinuria, and left ventricular mass index when compared with the other two groups. In regression analysis, eGFR and PWv were detected as the predictors of post-transplantation CRP levels. ConclusionsFluctuating and high stable (>20 mg/L) post-transplant CRP levels predict eGFR, proteinuria, left ventricular mass index, and PWv after transplantation. Thus, CRP levels may be a useful marker to anticipate graft survival and cardiovascular morbidity in renal transplant recipients.

Pretransplant Serum Levels of C-Reactive Protein Predict Prognoses in Patients Undergoing Liver Transplantation for Hepatocellular Carcinoma

BackgroundPreoperative absolute C-reactive protein (CRP) has been shown to correlate with prognoses in various malignancies, including hepatocellular carcinoma (HCC). MethodsThe aim of this study was to investigate whether pretransplant CRP levels predict prognoses in patients undergoing liver transplantation (LT) for HCC. We retrospectively analyzed clinicopathological factors in 211 patients with available pretransplant serum CRP levels who underwent LT for HCC between January 2005 and April 2012. ResultsBy means of receiver operating characteristic curve analysis, a CRP level of >0.3 mg/dL was considered to be elevated. By multivariate analysis, the high CRP level, the maximal tumor size >5 cm, the presence of intrahepatic metastasis, and positive findings in pretransplant 18fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) were related to tumor recurrence, whereas the high CRP level, the presence of intrahepatic metastasis, and positive findings in pretransplant 18F-FDG PET/CT were related to poor overall survival. When subgroup analysis was conducted according to the Milan criteria, the high CRP level was an independent factor for predicting poor outcomes in patients with HCC beyond the Milan criteria (P = .001 for recurrence-free survival and P = .010 for overall survival), and not for patients within the criteria. ConclusionsPretransplant serum CRP levels can predict prognoses in patients undergoing LT for HCC, especially in patients with HCC exceeding the Milan criteria.

Pre-Transplant C-Reactive Protein (CRP), Ferritin and Albumin As Biomarkers to Predict Transplant Related Mortality (TRM) after Allogeneic Hematopoietic Cell Transplant (HCT)

▪HCT entails substantial TRM justifying continued efforts to better risk stratify patients. Single institutional studies have suggested several clinically available biomarkers of CRP, ferritin and albumin influence TRM if not overall survival (OS). We sought to confirm the independent prognostic value of these biomarkers in a large multi-institutional cohort.The study population consisted of 784 adults with AML in remission (80%) or MDS (20%) undergoing unrelated donor HCT between 2008 and 2010 and available cryopreserved samples through the Center for International Blood and Marrow Transplant Research (CIBMTR) repository. CRP and ferritin were centrally quantified by ELISA from cryopreserved plasma whereas albumin levels obtained from center reported data. Correlation studies for biomarkers required log transformation of CRP and ferritin to produce a normal distribution. Multivariate models were fitted separately for each biomarker applying protocol specified thresholds generated from the literature of CRP > 10 mg/L, ferritin > 2500 ng/mL, albumin < 3.5 g/dL on TRM. Further analysis explored optimal cutpoints for this cohort for all significant clinical variables for TRM.HCT characteristics included a median age of 50 (range 18-78) years, HCT-CI (co-morbidity index) 3 or more in 35%, single allele/antigen mismatch (7/8) in 23%, PB as stem cell source in 83%, and myeloablative conditioning in 72%. Biomarker data were available in 783, 781 and 695 cases for CRP, ferritin and albumin respectively. The median values and ranges for each biomarker were as follows: 5.0 mg/L (0.3 - 316) for CRP, 1148 ng/mL (51 – 14,298) for ferritin and 3.6 g/dL (0.6-5.3) for albumin. Log transformed CRP and ferritin showed a modest correlation (r=0.35, P<0.001), and log CRP was marginally associated with albumin (r=-0.12, P=0.002). HCT-CI had no correlation to CRP and albumin. Higher ferritin was associated with HCT-CI (P=0.014) and disease (P<.001). In the entire population, TRM and overall survival (OS) at 2 years were 23% and 54%, respectively. The table shows the independent association of each biomarker with TRM and OS. Ferritin had no association with these outcomes but only 12% had levels above 2500 by ELISA. The optimal cutpoints for TRM were defined as follows: CRP > 3.67 (HR=1.75, P=0.001); albumin < 3.4 (HR 1.70, P <0.001); and ferritin as a continuous variable (HR 1.30, P = 0.008). A risk score was created modeling optimal biomarker thresholds to predict TRM based on the following formula: risk score = 0.44633*I(CRP>3.67)+0.18330*ln(Ferritin)+0.44730*I(albumin<3.4), where “I” is an indicator function and represent 1 or 0 depending on the presence of the abnormal biomarker level in parenthesis. The risk score included adjustment for HCT-CI. The biomarkers did not influence the incidence of relapse or graft-versus-host disease with any of these models.Elevated CRP and ferritin and decreased albumin prior to HCT were associated with impaired transplant survival, primarily through higher TRM. Integration of a biomarker panel in clinical practice once validated can enhance risk-stratification, improve adjustment for comparative studies and point towards the design of biomarker driven trials.Abstract 422. Table:Multivariate analysis of TRM and OS for biomarkers, and biomarker panel risk score*Abnormal,N (%)Transplant related mortalityOverall SurvivalBiomarkerHR95% CIPHR95% CIPProtocol definedCRP >10 mg/L184 (24)1.521.11 – 2.070.0081.220.98 – 1.530.072Ferritin >2500 ng/mL93 (12)1.260.84 – 1.880.271.150.86 – 1.540.35Albumin < 3.5 g/dL290 (42)1.481.10 – 2.00.0101.391.13 – 1.720.002Optimal threshold, combined model**CRP >3.67 mg/L497 (64)1.561.11 – 2.190.0101.241.00 – 1.550.054Log(Ferritin), linearn/a1.200.99 – 1.460.071.201.04 – 1.380.010<3.4 g/dL203 (29.5)1.581.16 – 2.150.0041.371.10 – 1.720.005Biomarker Score**NLow (<1.5)2001.0--1.0Intermediate (1.5-2.0)3311.661.10-2.490.0151.381.06-1.800.017High (>2.0)1592.721.77-4.19<0.0012.011.51-2.70<0.001*biomarkers adjusted for significant covariates of BMI, disease, mismatch, and CMV serostatus and stratified on conditioning regimen**combined model includes all biomarkers and HCT-CI DisclosuresNo relevant conflicts of interest to declare.

Pretransplant C‐reactive Protein as A Prognostic Marker in Allogeneic Stem Cell Transplantation

We evaluated the prognostic role of baseline levels of C-reactive protein (CRP) as well as CRP levels during conditioning in patients undergoing myeloablative allogeneic stem cell transplantation (SCT). Furthermore, we studied the impact of baseline clinical factors and conditioning regimens on CRP levels in the same period. We conducted a population-based retrospective study of 349 patients undergoing SCT at the National Danish SCT centre between January 2000 and January 2009. CRP levels increased significantly during the conditioning and peaked at day -3 before infusion of the graft. Elevated CRP was associated with older age, non-malignant disease, reduced pretransplant Karnofsky score and high-risk leukaemia. By univariate and multivariate analyses, increased CRP levels (>10mg/l) before the start of treatment (day -7) and at the day of graft infusion (day 0) were associated with decreased overall survival [HR 1.35 (95%CL) (1.18-1.54); P<0.0001] and increased treatment-related mortality [1.5 (1.24-1.82); P<0.0001]. Similar findings were seen for mean CRP levels during the conditioning. CRP was not associated with risk of relapse or aGvHD in multivariate analysis. This study suggests that increased CRP levels before and during the conditioning are associated with baseline clinical factors and that elevated pretransplant CRP levels predict a poorer survival in SCT.

Inflammatory markers as selection criteria of hepatocellular carcinoma in living-donor liver transplantation.

To investigate that inflammatory markers can predict accurately the prognosis of hepatocelluar carcinoma (HCC) patients in living-donor liver transplantation (LDLT). From October 2000 to November 2011, 224 patients who underwent living donor liver transplantation for HCC at our institution were enrolled in this study. We analyzed disease-free survival (DFS) and overall survival (OS) after LT in patients with HCC and designed a new score model using pretransplant neutrophil-lymphocyte ratio (NLR) and C-reactive protein (CRP). The DFS and OS in patients with an NLR level ≥ 6.0 or CRP level ≥ 1.0 were significantly worse than those of patients with an NLR level < 6.0 or CRP level < 1.0 (P = 0.049, P = 0.003 for NLR and P = 0.010, P < 0.001 for CRP, respectively). Using a new score model using the pretransplant NLR and CRP, we can differentiate HCC patients beyond the Milan criteria with a good prognosis from those with a poor prognosis. Combined with the Milan criteria, new score model using NLR and CRP represent new selection criteria for LDLT candidates with HCC, especially beyond the Milan criteria.

Comorbidity Measures In Ex Vivo T Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation (HCT)

Clinical comorbidity measures enhance the estimates of HCT tolerance and outcomes, thereby aiding therapeutic decisions. Ex vivo T cell depletion (TCD) of the graft reduces the risk of graft-versus-host disease and improves the tolerability of allogeneic transplantation in patients with impaired pretransplant performance. However, prediction tools such as the hematopoietic cell transplantation-specific comorbidity index (HCT-CI), have only been validated in conventional T-replete HCT. To improve outcome prediction in TCD transplants we therefore evaluated published comorbidity measures and other potential biomarkers of outcome in a series of myeloablative TCD transplant recipients. Pre transplant (week -2) factors measured were: HCT-CI, ECOG performance status, serum C-reactive protein (CRP), albumin (ALB), pre-albumin (PAB), ferritin, absolute lymphocyte counts (ALC), and absolute lymphocyte / monocyte ratio (LMR). CRP was also studied serially post transplant. CRP increased after conditioning, peaked (p =0.0001) in the first week of HCT, with recovery to baseline at 5 weeks post-HCT. We evaluated outcomes in a cohort of 79 patients in our institute with hematological malignancies receiving myeloablative total-body irradiation, and an HLA-identical sibling peripheral blood HCT, T cell depleted using Miltenyi CD34+ selection. The median age of recipients was 43 years (range 13-68 years). Of the 79, 34 (43%) had standard risk disease, and 45 (57%) recipients had high-risk disease. At a median follow up of ∼ 5 years, overall survival (OS) was 42.9% and nonrelapse mortality (NRM) was 33.9%. Comorbidity measures were first screened to eliminate highly-correlated covariates. Univariate Cox regression models were used to identify significant factors (p<0.05) associated with OS and NRM (with relapse as a competing risk), which were then further evaluated by multivariable Cox regression models. In the initial analysis we eliminated pre-HCT ECOG (94% were ECOG 0) and ferritin (median 1408 mcg/L, range 11-1444), which were highly correlated (p =0.003) to the HCT-CI score (median 3, range 0-9). Similarly, ALB (median 3.9 g/L, range 2.1-5.1, p = 0.002), PAB (median 25.6 mg/dL, range 6.9-56, p =0.001) and ferritin levels (p =0.005) were excluded as highly correlated to the pre-HCT CRP (preCRP) (median 5.8 mg/L, range 0.92-96.8). CRP levels measured at 2 weeks post transplant (postCRP) (median 10.4 mg/L, range 1.9-180) and ALC (median 0.96 K/uL, range 0.02-104.6) were not correlated to the pretransplant CRP. The independent pretransplant comorbidity variables identified for further testing were HCT-CI, preCRP, post CRP, ALC and LMR. In univariable analysis of OS, significant co-variates were HCT-CI scores ≥ 5 (HR 2.09 p= 0.02), preCRP (HR=1.016, p=0.07, a trend), postCRP (HR=1.014, p<0.001) and LMR ≤ 1.3 (HR=2.04, p= 0.04). In multivariable models of OS, postCRP ≥ 15 (HR 2.39, p =0.009) and LMR ≤ 1.3 (HR 2.25, p =0.04) retained significance. Confining the model to pretransplant data, then significant factors were pre CRP (HR 1.024 p= 0.02), HCT-CI≥5 (HR 2.08 p= 0.03) and LMR ≤1.3 (HR 2.43 p= 0.02). In univariable analysis of NRM, only continuous postCRP and postCRP ≥10 were significantly associated with NRM (HR=2.5, p =0.03) and in multivariable modeling of NRM, only postCRP ≥10 (HR=2.57, p=0.04) or continuous postCRP (HR=1.018, p=0.004) was found to be significant. LMR ≤ 1.3 and ECOG > 0 were found to be significantly associated with the cumulative incidence of relapse (both p=0.01). In conclusion, this is the first study to explore comorbidity scores and biomarkers to predict outcome after ex vivo TCD HCT. Our results suggest that HCT-CI score, preCRP, postCRP and the LMR are important independent clinical predictors of OS and NRM in TCD HCT. Disclosures:No relevant conflicts of interest to declare.

Prognostic role of pre‐transplantation serum C‐reactive protein levels in patients with acute leukemia undergoing myeloablative allogeneic stem cell transplantation

The aim of this study was to identify indicators of outcome prior to transplantation in allogeneic hematopoietic stem cell transplantation (HCT). Clinical data of 106 patients with acute leukemia were retrospectively analyzed. We examined the role of pre-conditioning serum C-reactive protein (CRP) and ferritin levels, HCT-CI and European Group for Blood and Marrow Transplantation (EBMT) scores on transplant toxicities, transplant-related mortality (TRM), progression-free survival (PFS), and overall survival (OS). High pre-conditioning serum CRP levels showed a positive correlation with higher EBMT scores (p < 0.001), HCT-CI (p = 0.004), and ferritin levels (p < 0.001). In univariate Cox regression analysis, serum CRP ≥10 mg/L, serum ferritin ≥1500 ng/mL, and HCT-CI ≥3 had a significant adverse effect on OS. Serum CRP ≥10 mg/L and HCT-CI ≥3 predicted increased risk of TRM in univariate analysis. Multivariate Cox regression analysis showed that HCT-CI score ≥3 independently predicted increased risk of TRM and CRP ≥10 mg/L predicted increased risk of disease progression. Although CRP lost its significance on TRM in multivariate analysis, as an inexpensive and readily available serum biomarker of inflammation, the prognostic role of pre-transplant CRP levels should be analyzed in selected diseases and increased number of patient groups.

C-Reactive Protein and Cardiovascular Diseases

C-reactive protein (CRP) is a unique risk marker and plays a role in the pathogenesis of inflammation and atherosclerosis. It is synthesized and secreted mainly by hepatocytes in response to interleukin-6 (IL-6) and either IL-1 or tumor necrosis factor-alpha. The average plasma half life of CRP is 19 hours. CRP activates complement, increases phagocytic activity of neutrophils, increases respiratory burst of neutrophils, and induces expression of adhesion molecules, synthesis of tissue factor, cytokines from monocytes and platelet aggregation. CRP is involved in development of atherosclerosis and thrombosis. High sensitive-CRP (hs-CRP) is a very novel biochemical marker. It is elevated in various conditions including: inflammation both acute and chronic, acute myocardial infarction, unstable angina, peripheral vascular diseases, diabetes, renal disease, hypertension, and cardiopulmonary bypass. A positive association has been reported between CRP levels and age, smoking, body mass, total cholesterol, lipoprotein a [Lp(a)], homocysteine and fibrinogen. It has a predictive value for the development of peripheral vascular disease, restenosis following percutaneous coronary interventions with or without stent implantation, and complications following cardiopulmonary bypass. Preprocedural high levels of plasma CRP are associated with high incidence of late adverse events (composite of cardiac death, nonfatal myocardial infarction, clinical occurrence of symptoms, progression of significant coronary lesion in vessels other then treated ones) after successful coronary stenting. Baseline levels of CRP predict risk of future myocardial infarction, and stroke in apparently healthy middle-aged men and women. CRP levels predict atherosclerotic vascular disease in patients with end-stage renal disease. Increased pretransplant CRP levels are associated with higher risk of acute rejection in transplant recipients. Various strategies to reduce the adverse effects of CRP have been discussed.

Is inflammation prior to renal transplantation predictive for cardiovascular and renal outcomes?

ObjectivesMarkers of non-specific inflammation, such as C-reactive protein (CRP) or leukocyte count are increased in end-stage renal disease patients. Recent studies have shown positive associations between inflammatory markers and cardiovascular mortality in kidney transplant recipients, but these analyses had been limited by sample size. The aim of our study was to determine the association between pretransplant CRP levels and leukocyte counts with posttransplant outcome in a prospectively enrolled cohort of kidney transplant recipients. Methods459 consecutive patients transplanted from July 1995 to December 2007 were analyzed. Both markers were obtained prior to transplantation and patients were grouped according to baseline CRP levels (<5mg/l or ≥5mg/l) or leukocyte counts (<10,000/μl or ≥10,000/μl). ResultsMajor cardiac events were associated with elevated pretransplant CRP levels (p<0.00003) but not leukocyte counts. Furthermore, more acute rejection episodes within 4 weeks or 6 months, as well as a lower probability of survival at 6 months were found in patients with elevated pretransplant CRP levels or leukocyte counts. ConclusionElevated pretransplant serum CRP level is a risk predictor for major cardiac events in renal transplant patients. It is also predictive, besides leukocyte counts, for acute rejection episodes. Elevated CRP levels and initial high leukocyte counts may prove to be useful markers for posttransplant course and warrant the close follow-up of such patients.

Obesity, Adiponectin and Inflammation as Predictors of New-Onset Diabetes Mellitus After Kidney Transplantation

The high incidence of new-onset diabetes mellitus after transplantation (NODAT) suggests the need to find new factors to explain the pathogenesis. Our objectives were (1) to confirm that low levels of pre-transplant adiponectin are an independent risk factor for the development of NODAT in a larger transplanted population; (2) to analyze whether adiponectin is a better predictor of NODAT than other inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and pregnancy-associated plasma protein A (PAPP-A)) and (3) to assess the relationship between obesity, inflammatory markers and NODAT. One hundred ninety-nine non-diabetic patients (128 men; age: 53 +/- 11 years; body mass index (BMI) 24.98 +/- 3.76 kg/m2) were included. Pre-transplant plasma glucose, insulin, adiponectin, CRP, TNF-alpha, IL-6 and PAPP-A were measured. Forty-five patients developed NODAT. Patients with NODAT had a greater BMI (p = 0.005). Adiponectin was lower (p < 0.001) and CRP higher (p = 0.032) in patients with NODAT. Multivariate logistic regression and Cox analysis showed that the calcineurin inhibitor used, pre-transplant BMI and adiponectin were predictors of NODAT. ROC analysis showed that an adiponectin concentration of 11.4 microg/mL had a significant negative prediction for NODAT risk (sensitivity: 81% and specificity: 70%). Of the inflammatory markers studied, adiponectin proved to be an independent predictor of NODAT.