Abstract 2308: Conventional Aortic Valve Replacement in Very Elderly Patients

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Gerald M Lawrie ◽  
Elizabeth A Earle ◽  
Nan R Earle
Keyword(s):  
Risk Factors ◽  
Regression Analysis ◽  
High Risk ◽  
Cox Regression ◽  
Bacterial Endocarditis ◽  
Very Elderly ◽  
Conventional Surgery ◽  
Perioperative Mortality ◽  
Cox Regression Analysis ◽  
Valve Size

Suboptimal early and late results of percutaneous AVR have been justified by its use in patients claimed to be at high risk for conventional surgery, particularly the very elderly. We performed an analysis to identify which risk factors in conventional AVR patients are most predictive of mortality and to quantify those risk factors in order to provide a realistic baseline for comparison. We analyzed the outcome of surgery in 1168 patients operated on over a 31 year period on one service. Of those patients, 50 suffered perioperative mortality. Of those, 54% (27/50) were male vs. 62% (699/1118) who did not suffer perioperative mortality and 32% (16/50) vs 22% (242/1118) were >76 yrs old; 21% (9/43) vs. 25% (241/982) had diabetes, and 9.3% (9/43) vs. 5.5 (54/982) had bacterial endocarditis (all p=NS); 22% (11/50) vs. 11% (122/1118) had a prior MI (p=0.0152); 26% (13/50) vs 11% (118/1118) had a prior CAB (p=0.0007); 46% (23/49) vs 29% (322/1118) had a concurrent CAB (p=0.0063); mean EF of 44.50±18.26 vs. 53.33±13.90 (p<0.0001); and mean replacement valve size of 20.69±2.14 vs. 21.75±2.46 (p=0.0031). Logistic regression analysis identified prior CAB (odds ratio (OR) 1.65. p<0.01), concurrent CAB (OR 1.63, p<0.01), bacterial endocarditis (OR 1.85, p<0.05) and replacement valve size (OR 0.81, p<0.01 – larger size is protective) as predictors of perioperative mortality. Age was not a predictor of perioperative mortality. Cox regression analysis for factors predictive of overall mortality identified age (relative risk (RR)1.046, 4.6%/yr, p<0.0001) preop EF (RR 0.982, decrease risk of 1.8%/1% increase EF, p<0.0001), diabetes (RR 1.254, p=0.0031, 25% increase risk with diabetes), and replacement valve size (RR 0.889, p=0.0004, 11.1% decreased risk/mm valve size.) These data suggest that even in high-risk patients, perioperative mortality is relatively low and is not predicted by age alone; therefore conventional surgery should be seriously considered in almost all patients. Age is only one of several risk factors which should be evaluated.

scholarly journals Risk Factors for Leukemic Transformation Among 1,306 Patients with Primary Myelofibrosis: Mutations Predict Early Events

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3044-3044
Author(s):  
Rangit Reddy Vallapureddy ◽  
Mythri Mudireddy ◽  
Natasha Szuber ◽  
Domenico Penna ◽  
Maura Nicolosi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Regression Analysis ◽  
High Risk ◽  
Cox Regression ◽  
Primary Myelofibrosis ◽  
Idh1 Mutation ◽  
Severe Anemia ◽  
Cox Regression Analysis ◽  
Version 2.0

Abstract Background: Current prognostic models in primary myelofibrosis (PMF) target overall survival (OS) and utilize MIPSS70 (mutation-enhanced international prognostic scoring system for transplant-age patients), MIPSS70+ version 2.0 (karyotype-enhanced MIPSS70) and GIPSS (genetically-inspired prognostic scoring system, which is based on mutations and karyotype) (JCO 2018;36:310; JCO doi: 10.1200/JCO.2018.78.9867; Leukemia. 2018;doi:10.1038/s41375-018-0107). In the current study, we used logistic regression statistics to identify risk factors for leukemic transformation (LT) within 5 years of diagnosis/referral (i.e. early events) and also performed Cox regression analysis of overall leukemia-free survival (LFS). Methods : Study patients were recruited from the Mayo Clinic, Rochester, MN, USA. Diagnoses of LT and chronic phase PMF were confirmed by both clinical and bone marrow examinations, in line with the 2016 World Health Organization criteria (Blood. 2016;127:2391); specifically, LT required presence of ≥20% blasts in the peripheral blood (PB) or bone marrow (BM) (Blood 2016;127:2391). Statistical analyses considered clinical and laboratory data collected at the time of initial PMF diagnosis or Mayo Clinic referral point. Logistic regression statistics was used to identify predictors of LT at 5 years from initial diagnosis/referral; in the particular method, patients with documented LT within 5 years were "uncensored" while those followed up for at least 5 years, without developing LT, were "censored"; the analysis excluded patients without LT and not followed for at least 5 years. In addition, Cox regression analysis was performed to identify risk factors for overall LFS. The JMP® Pro 13.0.0 software from SAS Institute, Cary, NC, USA, was used for all calculations. Results: 1,306 patients with PMF (median age 65 years; 63% males) were included in the current study; MIPSS70+ version 2.0 risk distribution was 20% very high risk, 41% high risk, 19% intermediate risk, 16% low risk and 4% very low risk. 149 (11%) patients were documented to experience LT, and compared to the remaining patients (n=1157), they were more likely to be males (p=0.02) and mutated for ASXL1 (p=0.01), SRSF2 (0.001) and IDH1 (0.02) and present with higher risk MIPSS70+ version 2.0 (p=0.02). Multivariable logistic regression identified the following as predictors of LT in the first 5 years of disease: IDH1 mutation (odds ratio; OR 78.4), very high risk (VHR) karyotype (OR 57.6), ASXL1 mutation (OR 15.1), age >70 years (OR 13.3), SRSF2 mutation (OR 8.5), male sex (OR 6.9), PB blasts ≥3% (OR 5.4), presence of moderate or severe anemia, adjusted for sex (OR 3.6) and constitutional symptoms (OR 3.1). On Cox regression analysis, the following were associated with inferior LFS: IDH1 mutation (HR 4.3), PB blasts ≥3% (HR 3.3), SRSF2 mutation (HR 3.0), age >70 years (HR 2.1), ASXL1 mutation (HR 2.0) and presence of moderate or severe anemia, adjusted for sex (HR 1.9). Subsequently, HR-based risk point allocation resulted in highly discriminating LT predictive model with HR (95% CI) of 39.4 (10.8-114) for high risk and 4.1 (2.4-7.3) for intermediate risk (Figure 1). Conclusions: The current study identifies IDH1 mutation as a main predictor of LT in PMF. Our study also implicates SRSF2 and ASXL1 mutations and VHR karyotype as other genetic markers of early LT. Other independent contributors of early LT and inferior LFS, overall, included PB blasts ≥3%, moderate to severe anemia and older age. We provide LT prediction model, based on these variables, with leukemia risk ranging from 8% to 57%. Disclosures No relevant conflicts of interest to declare.

scholarly journals A Prognostic Model for Patients With Gastric Signet Ring Cell Carcinoma

2021 ◽  
Vol 20 ◽  
pp. 153303382110279
Author(s):  
Qinping Guo ◽  
Yinquan Wang ◽  
Jie An ◽  
Siben Wang ◽  
Xiushan Dong ◽  
...  
Keyword(s):  
Risk Factors ◽  
Regression Analysis ◽  
Cox Regression ◽  
Signet Ring Cell Carcinoma ◽  
Signet Ring Cell ◽  
Training Set ◽  
Cox Regression Analysis ◽  
Signet Ring ◽  
Ring Cell ◽  
Independent Risk Factors

Background: The aim of our study was to develop a nomogram model to predict overall survival (OS) and cancer-specific survival (CSS) in patients with gastric signet ring cell carcinoma (GSRC). Methods: GSRC patients from 2004 to 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database and randomly assigned to the training and validation sets. Multivariate Cox regression analyses screened for OS and CSS independent risk factors and nomograms were constructed. Results: A total of 7,149 eligible GSRC patients were identified, including 4,766 in the training set and 2,383 in the validation set. Multivariate Cox regression analysis showed that gender, marital status, race, AJCC stage, TNM stage, surgery and chemotherapy were independent risk factors for both OS and CSS. Based on the results of the multivariate Cox regression analysis, prognostic nomograms were constructed for OS and CSS. In the training set, the C-index was 0.754 (95% CI = 0.746-0.762) for the OS nomogram and 0.762 (95% CI: 0.753-0.771) for the CSS nomogram. In the internal validation, the C-index for the OS nomogram was 0.758 (95% CI: 0.746-0.770), while the C-index for the CSS nomogram was 0.762 (95% CI: 0.749-0.775). Compared with TNM stage and SEER stage, the nomogram had better predictive ability. In addition, the calibration curves also showed good consistency between the predicted and actual 3-year and 5-year OS and CSS. Conclusion: The nomogram can effectively predict OS and CSS in patients with GSRC, which may help clinicians to personalize prognostic assessments and clinical decisions.

scholarly journals Development of prognosis model for colon cancer based on autophagy-related genes

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Xu Wang ◽  
Yuanmin Xu ◽  
Ting Li ◽  
Bo Chen ◽  
Wenqi Yang
Keyword(s):  
Colon Cancer ◽  
Regression Analysis ◽  
High Risk ◽  
Cancer Patients ◽  
Risk Score ◽  
Cox Regression ◽  
Patient Survival ◽  
Expression Profiles ◽  
Cox Regression Analysis ◽  
Risk Patients

Abstract Background Autophagy is an orderly catabolic process for degrading and removing unnecessary or dysfunctional cellular components such as proteins and organelles. Although autophagy is known to play an important role in various types of cancer, the effects of autophagy-related genes (ARGs) on colon cancer have not been well studied. Methods Expression profiles from ARGs in 457 colon cancer patients were retrieved from the TCGA database (https://portal.gdc.cancer.gov). Differentially expressed ARGs and ARGs related to overall patient survival were identified. Cox proportional-hazard models were used to investigate the association between ARG expression profiles and patient prognosis. Results Twenty ARGs were significantly associated with the overall survival of colon cancer patients. Five of these ARGs had a mutation rate ≥ 3%. Patients were divided into high-risk and low-risk groups based on Cox regression analysis of 8 ARGs. Low-risk patients had a significantly longer survival time than high-risk patients (p < 0.001). Univariate and multivariate Cox regression analysis showed that the resulting risk score, which was associated with infiltration depth and metastasis, could be an independent predictor of patient survival. A nomogram was established to predict 1-, 3-, and 5-year survival of colon cancer patients based on 5 independent prognosis factors, including the risk score. The prognostic nomogram with online webserver was more effective and convenient to provide information for researchers and clinicians. Conclusion The 8 ARGs can be used to predict the prognosis of patients and provide information for their individualized treatment.

scholarly journals A Risk Signature of Nine Autophagy-Related Genes Associated With Immune Microenvironment and Clinical Prognosis in Wilms Tumor

2021 ◽  
Author(s):  
Shaopei Ye ◽  
Wenbin Tang ◽  
Ke Huang
Keyword(s):  
Regression Analysis ◽  
High Risk ◽  
Risk Score ◽  
Cox Regression ◽  
Wilms Tumor ◽  
Risk Group ◽  
High Risk Group ◽  
Differentially Expressed ◽  
Clinical Prognosis ◽  
Cox Regression Analysis

Abstract Background: Autophagy is a biological process to eliminate dysfunctional organelles, aggregates or even long-lived proteins. . Nevertheless, the potential function and prognostic values of autophagy in Wilms Tumor (WT) are complex and remain to be clarifed. Therefore, we proposed to systematically examine the roles of autophagy-associated genes (ARGs) in WT.Methods: Here, we obtained differentially expressed autophagy-related genes (ARGs) between healthy and Wilms tumor from Therapeutically Applicable Research To Generate Effective Treatments(TARGET) and The Cancer Genome Atlas (TCGA) database. The functionalities of the differentially expressed ARGs were analyzed using Gene Ontology. Then univariate COX regression analysis and multivariate COX regression analysis were performed to acquire nine autophagy genes related to WT patients’ survival. According to the risk score, the patients were divided into high-risk and low-risk groups. The Kaplan-Meier curve demonstrated that patients with a high-risk score tend to have a poor prognosis.Results: Eighteen DEARGs were identifed, and nine ARGs were fnally utilized to establish the FAGs based signature in the TCGA cohort. we found that patients in the high-risk group were associated with mutations in TP53. We further conducted CIBERSORT analysis, and found that the infiltration of Macrophage M1 was increased in the high-risk group. Finally, the expression levels of crucial ARGs were verifed by the experiment, which were consistent with our bioinformatics analysis.Conclusions: we emphasized the clinical significance of autophagy in WT, established a prediction system based on autophagy, and identified a promising therapeutic target of autophagy for WT.

scholarly journals Role of Disease Modifying Treatment in the Risk of Alloimmunization in Transfused Patients with Myelodysplastic Syndromes: A Population-Based Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4253-4253
Author(s):  
Hanne Rozema ◽  
Robby Kibbelaar ◽  
Nic Veeger ◽  
Mels Hoogendoorn ◽  
Eric van Roon
Keyword(s):  
Risk Factors ◽  
Regression Analysis ◽  
Cox Regression ◽  
Population Based ◽  
Incidence Rates ◽  
Blood Products ◽  
Cox Regression Analysis ◽  
In The Beginning ◽  
Observation Period

The majority of patients with myelodysplastic syndromes (MDS) require regular red blood cell (RBC) transfusions. Alloimmunization (AI) against blood products is an adverse event, causing time-consuming RBC compatibility testing. The reported incidence of AI in MDS patients varies greatly. Even though different studies on AI in MDS patients have been performed, there are still knowledge gaps. Current literature has not yet fully identified the risk factors and dynamics of AI in individual patients, nor has the influence of disease modifying treatment (DMT) been explored. Therefore, we performed this study to evaluate the effect of DMT on AI. An observational, population-based study, using the HemoBase registry, was performed including all newly diagnosed MDS patients between 2005 and 2017 in Friesland, a province of the Netherlands. All available information about treatment and transfusions, including transfusion dates, types, and treatment regimens, was collected from the electronic health records and laboratory systems. Follow-up occurred through March 2019. For our patient cohort, blood products were matched for AB0 and RhD, and transfused per the 'type and screen' policy (i.e. electronic matching of blood group phenotype between patient and donor). After a positive antibody screening, antibody identification and Rh/K phenotyping was performed and subsequent blood products were (cross)matched accordingly. The observation period was counted from first transfusion until last transfusion or first AI event. Univariate analyses and cumulative frequency distributions were performed to study possible risk factors and dynamics of AI. DMT was defined as hypomethylating agents, lenalidomide, chemotherapy and monoclonal antibodies. The effect of DMT as a temporary risk period on the risk of AI was estimated with incidence rates, relative risks (RR) and hazard ratios (HR) using a cox regression analysis. Follow-up was limited to 24 months for the cox regression analysis to avoid possible bias by survival differences. Statistical analyses were performed using IBM SPSS 24 and SAS 9.4. Out of 292 MDS patients, 236 patients received transfusions and were included in this study, covering 463 years of follow-up. AI occurred in 24 patients (10%). AI occurred mostly in the beginning of the observation period: Eighteen patients (75%) were alloimmunized after receiving 20 units of RBCs, whereas 22 patients (92%) showed AI after 45 units of RBCs (Figure 1). We found no significant risk factors for AI in MDS patients at baseline. DMT was given to 67 patients (28%) during the observation period. Patients on DMT received more RBC transfusions than patients that did not receive DMT (median of 33 (range: 3-154) and 11 (range: 0-322) RBC units respectively, p<0,001). Four AI events (6%) occurred in patients on DMT and 20 AI events (12%) occurred in patients not on DMT. Cox regression analysis of the first 24 months of follow-up showed an HR of 0.30 (95% CI: 0.07-1.31; p=0.11). The incidence rates per 100 person-years were 3.19 and 5.92 respectively. The corresponding RR was 0.54 (95% CI: 0.16-1.48; p=0.26). Based on our results, we conclude that the incidence of AI in an unselected, real world MDS population receiving RBC transfusions is 10% and predominantly occurred in the beginning of follow-up. Risk factors for AI at baseline could not be identified. Our data showed that patients on DMT received significantly more RBC transfusions but were less susceptible to AI. Therefore, extensive matching of blood products may not be necessary for patients on DMT. Larger studies are needed to confirm the protective effect of DMT on AI. Disclosures Rozema: Celgene: Other: Financial support for visiting MDS Foundation conference.

scholarly journals Incidence, Survival, and Associated Factors Estimation in Osteosarcoma Patients with Lung Metastasis: A Single-center Experience of 11 Years in Tianjin, China

2021 ◽  
Author(s):  
Chao Zhang ◽  
Haixiao Wu ◽  
Guijun Xu ◽  
Wenjuan Ma ◽  
Lisha Qi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Regression Analysis ◽  
Prognostic Factors ◽  
Lung Metastasis ◽  
Associated Factors ◽  
Cox Regression ◽  
Cancer Center ◽  
Single Center ◽  
Cox Regression Analysis

Abstract Background: Osteosarcoma is the most common primary malignant bone tumor. The current study was conducted to describe the general condition of patients with primary osteosarcoma in a single cancer center in Tianjin, China and to investigate the associated factors in osteosarcoma patients with lung metastasis. Methods: From February 2009 to October 2020, patients from Tianjin Medical University Cancer Institute and Hospital, China were retrospectively analyzed. The Kaplan–Meier method was used to evaluate the overall survival of osteosarcoma patients. Prognostic factors of patients with osteosarcoma were identified by the Cox proportional hazard regression analysis. Risk factor of lung metastasis in osteosarcoma were investigated by the logistic regression model. Results: A total of 203 patients were involved and 150 patients were successfully followed up for survival status. The 5-year survival rate of osteo-sarcoma patients was 70.0%. Surgery, bone and lung metastasis were the significant prognostic factors in multivariable Cox regression analysis. Twenty-one (10.3%) patients showed lung metastasis at the diagnosis of osteosarcoma and 67 (33%) lung metastases during the later course. T3 stage (OR=11.415, 95%CI 1.362-95.677, P=0.025) and synchronous bone metastasis (OR=6.437, 95%CI 1.69-24.51, P=0.006) were risk factors of synchronous lung metastasis occurrence. Good necrosis (≥90%, OR=0.097, 95%CI 0.028-0.332, P=0.000) and elevated Ki-67 (≥50%, OR=4.529, 95%CI 1.241-16.524, P=0.022) were proved to be significantly associated with metachronous lung metastasis occurrence. Conclusion: The overall survival, prognostic factors and risk factors for lung metastasis in this single center provided insight about osteosarcoma management.

Predictive value of ankle–brachial index for long-term events of ischemic stroke in hemodialysis patients

Vascular ◽  
2020 ◽  
pp. 170853812092595
Author(s):  
Kai-Ni Lee ◽  
Li-Ping Chou ◽  
Chi-Chu Liu ◽  
Tsang-Shan Chen ◽  
Eric Kim-Tai Lui ◽  
...  
Keyword(s):  
Risk Factors ◽  
Regression Analysis ◽  
Ischemic Stroke ◽  
Cox Regression ◽  
Ankle Brachial Index ◽  
Hemodialysis Patients ◽  
Serum Phosphate ◽  
Cox Regression Analysis

Objectives The ankle–brachial index is a noninvasive modality to evaluate atherosclerosis and is a predictive role for future cardiovascular events and mortality. However, few studies have evaluated its relation to long-term future ischemic stroke in hemodialysis patients. Therefore, we examined the relationship between ankle–brachial index and ischemic stroke events among hemodialysis patients in a seven-year follow-up. Methods A total of 84 patients were enrolled. Ankle–brachial index was assessed in January 2009. Primary outcomes included ischemic stroke. An ankle–brachial index < 0.9 was considered abnormal and 1.4 ≥ ankle–brachial index ≥ 0.9 to be normal ankle–brachial index. Results Mean values for ankle–brachial index were 0.98 ± 0.21at study entrance. In addition, 28 patients encountered ischemic stroke in the seven-year follow-up. In univariate Cox regression analysis, old age (hazard ratio (HR): 1.065, 95% confidence interval (CI): 1.030–1.102, p < 0.001), low seven-year averaged serum phosphate levels (HR: 0.473, 95% CI: 0.306–0.730, p = 0.001), and abnormal ankle–brachial index (HR: 0.035, 95% CI: 0.009–0.145, p < 0.001) were risk factors for ischemic stroke. In multivariate Cox regression analysis for significant variables in univariate analysis, abnormal ankle–brachial index (HR: 0.058, 95% CI: 0.012–0.279, p < 0.001) and low seven-year averaged serum phosphate levels (HR: 0.625, 95% CI: 0.404–0.968, p = 0.035) remained the risk factors for ischemic stroke. The risk of ischemic stroke was 3.783-fold in patients with abnormal ankle–brachial index compared with patients with normal ankle–brachial index (HR: 3.783, 95% CI: 1.731–8.269, p = 0.001). Conclusions These findings suggest that ankle–brachial index is an impressive predictor of future ischemic stroke among hemodialysis patients.

P0380INFECTION PROFILE AND ASSOCIATED RISK FACTORS IN AGGRESSIVE GLOMERULONEPHRITIS TREATED WITH INDUCTION AND MAINTENANCE REGIMENS OF IMMUNOSUPPRESSIVE THERAPY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Alexandra Vornicu ◽  
Bogdan Obrisca ◽  
Roxana Jurubita ◽  
Andreea Gabriella Andronesi ◽  
Bogdan Marian Sorohan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Regression Analysis ◽  
Cox Regression ◽  
Systemic Disease ◽  
Pulmonary Involvement ◽  
High Dose ◽  
Cox Regression Analysis ◽  
Oral Corticosteroids ◽  
Dose Oral ◽  
Associated Risk Factors

Abstract Background and Aims Infections remain an important contributor to the morbidity and mortality of immunosuppressive (IS) therapy in aggressive glomerulonephritis. We sought to investigate the infection profile and associated risk factors in a compiled cohort of patients with lupus nephritis (LN), cryoglobulinemic vasculitis (CryoVas) and ANCA-associated vasculitis (AAV) treated with induction and maintenance IS regimens. Method A total of 162 patients (101 with LN, 24 with CryoVas and 37 with AAV) were retrospectively reviewed for any infection that occurred from initiation of induction therapy. Infections were graded (1-5) according to the Common Terminology Criteria for Adverse Events. Infection site and type of microorganism were also recorded. Univariate and multivariate Cox proportional hazard regression analysis were performed in order to identify independent risk factors for infection. Results Eighty-two patients (50.6%) had at least one infection with a total 179 episodes of infection occurring during a median follow-up of 12 months (IQR:4-36.25 months). The majority of patients (64 of 82) had infections during the first 24 months since IS treatment initiation with a 24-month infection-free rate of 55%. The most common site was lung infection (in 32.7% of patients), while 39.5% of patients had bacterial infections (1.8% with Mycobacterium tuberculosis). 36.7% of patients had severe infections (grade 3 or higher) with 4.4% of infection-related deaths (8 patients). The most common induction regimen was cyclophosphamide in addition to corticosteroids (62%), while 43% received either mycophenolate mofetil or azathioprine in addition to corticosteroids as a maintenance regimen. In univariate Cox regression analysis, chronic obstructive pulmonary disease (HR 3.91; 95% CI, 1.76-8.68, p=0.001), pulmonary involvement in the setting of systemic disease (HR 2.35; 95% CI, 1.26-4.37, p=0.007), pulse methylprednisolone (HR 2.7; 95% CI, 1.7-4.31, p=0.001) and high-dose (≥30 mg/day) oral corticosteroids (HR 3.38; 95% CI, 2.11-5.43, p=0.001) were risk factors for infection. In multivariate Cox regression analysis, high-dose oral corticosteroids (HR 2.67; 95% CI, 1.5-4.76, p=0.001) remained an independent predictor of infection risk. Of the risk factors associated with severe infections (grade 3 or higher), in univariate analysis we identified pulmonary involvement in the setting of systemic disease (HR 3.65; 95% CI, 1.72-7.77, p=0.001), pulse methylprednisolone (HR 3.56; 95% CI, 1.7-7.3, p=0.001), high-dose (≥30 mg/day) oral corticosteroids (HR 3.56; 95% CI, 1.77-7.16, p=0.001), estimated GFR (HR 0.98; 95% CI, 0.98-0.99, p=0.01) and AAV (by comparison to CryoVas and LN) (HR 2.81; 95% CI, 1.39-5.66, p=0.004) as risk factors for infection. After multivariate adjustment, pulmonary involvement in the setting of systemic disease (HR 2.38; 95% CI, 1.01-5.73, p=0.05) and high-dose oral corticosteroids (HR 2.44; 95% CI, 1.04-5.72, p=0.04) were identified as independent predictors of infection risk. Conclusion Infections occur frequently with current immunosuppressive regimens in aggressive glomerulonephritis. In addition to pulmonary involvement in the setting of systemic disease, a high dose corticosteroid regimen was the most significant risk factor for infection.

Natural History, Risk Factors and Prognostic Impact of Graft-Versus-Host Disease Classified According to the National Institute of Health Criteria in Patients Receiving Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 899-899 ◽  
Author(s):  
Theis H Terwey ◽  
Arturo Vega-Ruiz ◽  
Philipp G. Hemmati ◽  
Peter Martus ◽  
Ekkehart Dietz ◽  
...  
Keyword(s):  
Risk Factors ◽  
Regression Analysis ◽  
Risk Factor ◽  
Cumulative Incidence ◽  
Cox Regression ◽  
Prognostic Impact ◽  
Cox Regression Analysis ◽  
Graft Versus Host ◽  
Organ Manifestations ◽  
Grade Iii

Abstract Abstract 899 Introduction: The classic definition of acute (aGVHD) and chronic graft-versus-host disease (cGVHD) was based on a cut-off day 100 after transplantation, but this did not reflect that aGVHD can occur later and that symptoms of aGVHD and cGVHD can occur simultaneously. In 2005 a NIH consensus classification was proposed which included 1) classic aGVHD, occurring before day 100, 2) persistent, recurrent or late aGVHD occurring thereafter, 3) classic cGVHD and 4) an overlap syndrome with simultaneous features of aGVHD and cGVHD. Only few studies have evaluated this classification and no studies have determined the differential impact of reduced intensity (RIC) and myeloablative conditioning (MAC). Method: We retrospectively analyzed 202 AML patients who were transplanted between 1999 and 2008. 102 patients received RIC (generally 6×30 mg/m2 FLU, 4×4 mg/kg BU, 4×10 mg/kg ATG) and immunosuppression with CSA/MMF and 100 patients received MAC (generally 6×2 Gy TBI and 2×60 mg/kg CY) and CSA/MTX. Donors were HLA-matched related (n=82), -matched unrelated (n=88) or -mismatched (n=32). Result: Leukocyte recovery was faster after RIC than after MAC (14 vs. 19 days, P<0.001) but time to reach full donor chimerism was similar (60 vs. 56 days, P=0.12). The cumulative incidence of classic aGVHD was lower after RIC than after MAC (40 vs. 67%, P<0.001) and it occurred later (31 vs. 23 days, P=0.041). No difference was seen in organ manifestations and in the overall aGVHD grade. The cumulative incidence of late aGVHD was low and did not differ between RIC and MAC (9 vs. 7%, P=NS). 13/16 patients with late aGVHD had persistent or recurrent classic aGVHD and 3/16 had de novo late aGVHD. Late aGVHD was less severe after RIC (grade III/IV 22 vs. 86%, P=0.041). The first signs of cGVHD were observed on days 86 after RIC and 97 after MAC with median onset on days 167 and 237, respectively (P=NS). The cumulative incidence of cGVHD tended to be lower after RIC (36 vs. 51%, P=0.088) and it tended to be less severe. Organ manifestations were similar except for cGVHD of the joints and fascia which affected 11% of MAC but no RIC patients (P=0.0021). More than half of cGVHD cases were subclassified as overlap cGVHD with no significant differences between RIC and MAC (51 vs. 65%, P=0.26). In multivariate Cox regression analysis of the whole cohort the only significant risk factor for aGVHD was MAC (HR 2.33, 95%CI 1.51–3.59, p<0.001). In RIC patients the administration of bone marrow lead to less aGVHD (HR 0.13, 95%CI 0.016–0.98, P=0.047). The only relevant risk factor for late aGVHD was prior aGVHD (HR 3.65, 95%CI 1.040–12.81, P=0.043). The most important risk factors for cGVHD were prior aGVHD (HR 2.77, 95%CI 1.64–5.67, P<0.001), female-to-male transplantation (HR 1.94, 95%CI 1.12–3.35, P=0.017) and advanced disease (HR 1.95, 95%CI 1.2–3.1, P=0.018). In multivariate Cox regression analysis with GVHD as time-dependant covariate aGVHD grade III/IV (HR 2.41, 95%CI: 1.51–3.87, P=0.001) and late aGVHD grade III/IV (HR 3.037, 95%CI 1.29–7.18, P=0.011) were associated with inferior overall survival (OS) while moderate cGVHD had a positive effect (HR 0.42, 95%CI 0.18–0.97, P=0.043). Classic and overlap cGVHD had no differential prognostic impact. Conclusion: This study in AML patients shows that previously established GVHD risk factors remain valid for the new NIH classification. It also confirms the major impact of conditioning intensity on GVHD incidence, the negative prognostic impact of severe aGVHD and the benefit of moderate cGVHD. The new category late aGVHD may only include few patients but will allow more adequate allocation to therapies or clinical trials. Whether the subgroups classic and overlap cGVHD are clinically relevant remains to be determined. Disclosures: No relevant conflicts of interest to declare.

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