Higher Hematopoietic Cell Transplant Comorbidity Index (HCT-CI) Is Associated with Poor Psychosocial Health Pre-Autologous Stem Cell Transplantation (ASCT) in Lymphoma Patients

Abstract The assessment of pre-transplant comorbidities is crucial for risk-stratification and is a tool to guide clinical decisions in hematological malignancy patients (pts) undergoing evaluation for stem cell transplantation (SCT). The HCT-CI scale is commonly used to identify high risk patients pre-transplant as it is highly predictive of non-relapse mortality (NRM), severity of graft versus host disease and survival after allogeneic SCT (Sorror et al, Blood 2005; Sorror et al, Blood 2014). However, its role in ASCT remains undefined. In a Center for International Blood and Marrow Transplant Research analysis, HCT-CI score of ≥3 was prognostic for higher NRM and overall mortality in ASCT patients (Sorror et al, Biol. Blood Marrow Transplant 2015), but other single institution studies have failed to confirm this observation in lymphoma patients (Jaglowski et al, Bone Marrow Transplant 2014; Dahi et al, Biol. Blood Marrow Transplant 2014; Hosing et al, Ann. Oncol. 2008). No study has correlated HCT-CI with psychosocial functioning in the setting of ASCT. We conducted a retrospective study of 350 patients with Hodgkin (N=70) and non-Hodgkin Lymphoma (N=280) who underwent ASCT at our institution from January 2009 to June 2015. Based on their HCT-CI score, patients were categorized into low risk (score 0, N=90), intermediate risk (score 1-2, N=123) and high risk (score ≥3, N=137). Psychosocial Assessment of Candidates for Transplantation (PACT) scale (0-4: 0 being poor candidate for procedure and 4 being excellent candidate) (Foster et al. BMT 2009) was used for pre-transplant psychosocial risk assessment and was available for 235 pts. We analyzed the impact of HCT-CI on transplant outcomes and its correlation with PACT scores. Our cohort was predominantly male (63%), and Caucasian (93%) with a median age of 55 years (range 20-78). The majority of the pts (96%) had good performance status with an ECOG of 0-1. The primary diagnosis was NHL in 80%, with mostly advanced stage disease (80%), and no B symptoms (93%). Median time from diagnosis to ASCT was 16 months with 75% of the pts having received ≤2 prior therapies. The median annual income based on zip code was $49406 (range $18753-127312). Disease status prior to transplant was CR/PR in 93% of the subjects. Patient and disease characteristics were comparable among the 3 HCT-CI risk groups. Higher HCT-CI risk category was associated with a lower median household income (p=0.012), higher LDH (p=0.004), more days of apheresis (p=0.026) and lower CD34+ dose x106/kg (0.046). In relation to PACT scores, higher HCT-CI was associated with poor mental health (p<0.001), decreased coping skills (p<0.001), unhealthy lifestyle habits/sedentary life (p<0.001), decreased compliance with medications/medical advice (p=0.014) and inadequate medical/transplant knowledge (p=0.017) and lower final PACT score (p<0.001). Median follow up was 35 months with 100 observed deaths, of which 72 were attributed to relapse. The 5 year estimated relapse rate, NRM, relapse free survival (RFS) and overall survival (OS) in our cohort were 42%, 11%, 49% and 62% respectively. On univariate analysis, there was no significant difference between high vs. low/intermediate HCT-CI scores on 30 day readmission rates (OR 1.24, p=0.61), 100 day mortality (OR 1.12, p=0.86), incidence of secondary malignancy (HR 0.41, p=0.17), relapse rate (HR 0.92, p=0.64), relapse mortality (HR 1.35, p=0.20), NRM (HR 0.86, p=0.71), OS (HR 1.2, p=0.37) or RFS (HR 0.98, p=0.92). Though not statistically significant, the intermediate risk group was noted to have higher 100 day mortality and NRM compared to the low and high risk groups. To our knowledge, this is first study to correlate pre-transplant HCT-CI with PACT scores in lymphoma pts who underwent ASCT. Higher HCT-CI was associated with lower socioeconomic status, poor mental health and coping skills, unhealthy lifestyle habits, decreased medical/transplant knowledge and compliance. HCT-CI did not predict survival in our cohort. Further studies are needed to investigate the association between psychosocial risk factors and HCT-CI and define their combined utility in pre-transplant risk assessment in ASCT patients. Table Patient characteristics and HCT-CI risk categories Table. Patient characteristics and HCT-CI risk categories Figure Impact of HCT-CI on OS in ASCT patients Figure. Impact of HCT-CI on OS in ASCT patients Disclosures No relevant conflicts of interest to declare.

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A Peri-Implant Disease Risk Score for Patients with Dental Implants: Validation and the Influence of the Interval between Maintenance Appointments

Journal of Clinical Medicine ◽

10.3390/jcm8020252 ◽

2019 ◽

Vol 8 (2) ◽

pp. 252 ◽

Cited By ~ 4

Author(s):

Miguel de Araújo Nobre ◽

Francisco Salvado ◽

Paulo Nogueira ◽

Evangelista Rocha ◽

Peter Ilg ◽

...

Keyword(s):

High Risk ◽

Risk Score ◽

Disease Risk ◽

Disease Incidence ◽

Risk Groups ◽

Risk Profile ◽

Moderate Risk ◽

C Statistic ◽

Disease Risk Score ◽

Very High

Background: There is a need for tools that provide prediction of peri-implant disease. The purpose of this study was to validate a risk score for peri-implant disease and to assess the influence of the recall regimen in disease incidence based on a five-year retrospective cohort. Methods: Three hundred and fifty-three patients with 1238 implants were observed. A risk score was calculated from eight predictors and risk groups were established. Relative risk (RR) was estimated using logistic regression, and the c-statistic was calculated. The effect/impact of the recall regimen (≤ six months; > six months) on the incidence of peri-implant disease was evaluated for a subset of cases and matched controls. The RR and the proportional attributable risk (PAR) were estimated. Results: At baseline, patients fell into the following risk profiles: low-risk (n = 102, 28.9%), moderate-risk (n = 68, 19.3%), high-risk (n = 77, 21.8%), and very high-risk (n = 106, 30%). The incidence of peri-implant disease over five years was 24.1% (n = 85 patients). The RR for the risk groups was 5.52 (c-statistic = 0.858). The RR for a longer recall regimen was 1.06, corresponding to a PAR of 5.87%. Conclusions: The risk score for estimating peri-implant disease was validated and showed very good performance. Maintenance appointments of < six months or > six months did not influence the incidence of peri-implant disease when considering the matching of cases and controls by risk profile.

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Short-term risk stratification using CADILLAC risk score in patients with ST elevation myocardial infarction

European Heart Journal ◽

10.1093/ehjci/ehaa946.1352 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

T Satou ◽

H Kitahara ◽

K Ishikawa ◽

T Nakayama ◽

Y Fujimoto ◽

...

Keyword(s):

Myocardial Infarction ◽

High Risk ◽

Adverse Events ◽

Risk Score ◽

Risk Group ◽

Risk Groups ◽

Low Risk ◽

Short Term ◽

Recurrent Myocardial Infarction ◽

St Elevation

Abstract Background The recent reperfusion therapy for ST-elevation myocardial infarction (STEMI) has made the length of hospital stay shorter without adverse events. CADILLAC risk score is reportedly one of the risk scores predicting the long-term prognosis in STEMI patients. Purpose To invenstigate the usefulness of CADILLAC risk score for predicting short-term outcomes in STEMI patients. Methods Consecutive patients admitted to our university hospital and our medical center with STEMI (excluding shock, arrest case) who underwent primary PCI between January 2012 and April 2018 (n=387) were enrolled in this study. The patients were classified into 3 groups according to the CADILLAC risk score: low risk (n=176), intermediate risk (n=87), and high risk (n=124). Data on adverse events within 30 days after hospitalization, including in-hospital death, sustained ventricular arrhythmia, recurrent myocardial infarction, heart failure requiring intravenous treatment, stroke, or clinical hemorrhage, were collected. Results In the low risk group, adverse events within 30 days were significantly less observed, compared to the intermediate and high risk groups (n=13, 7.4% vs. n=13, 14.9% vs. n=58, 46.8%, p<0.001). In particular, all adverse events occurred within 3 days in the low risk group, although adverse events, such as heart failure (n=4), recurrent myocardial infarction (n=1), stroke (n=1), and gastrointestinal bleeding (n=1), were substantially observed after day 4 of hospitalization in the intermediate and high risk groups. Conclusions In STEMI patients with low CADILLAC risk score, better short-term prognosis was observed compared to the intermediate and high risk groups, and all adverse events occurred within 3 days of hospitalization, suggesting that discharge at day 4 might be safe in this study population. CADILLAC risk score may help stratify patient risk for short-term prognosis and adjust management of STEMI patients. Initial event occurrence timing Funding Acknowledgement Type of funding source: None

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A prognostic model based on seven immune-related genes predicts the overall survival of patients with hepatocellular carcinoma

BioData Mining ◽

10.1186/s13040-021-00261-y ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Qian Yan ◽

Wenjiang Zheng ◽

Boqing Wang ◽

Baoqian Ye ◽

Huiyan Luo ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

High Risk ◽

Risk Score ◽

Immune Cells ◽

Prognostic Model ◽

Risk Groups ◽

Low Risk ◽

Prognostic Performance ◽

Immune Related Genes

Abstract Background Hepatocellular carcinoma (HCC) is a disease with a high incidence and a poor prognosis. Growing amounts of evidence have shown that the immune system plays a critical role in the biological processes of HCC such as progression, recurrence, and metastasis, and some have discussed using it as a weapon against a variety of cancers. However, the impact of immune-related genes (IRGs) on the prognosis of HCC remains unclear. Methods Based on The Cancer Gene Atlas (TCGA) and Immunology Database and Analysis Portal (ImmPort) datasets, we integrated the ribonucleic acid (RNA) sequencing profiles of 424 HCC patients with IRGs to calculate immune-related differentially expressed genes (DEGs). Survival analysis was used to establish a prognostic model of survival- and immune-related DEGs. Based on genomic and clinicopathological data, we constructed a nomogram to predict the prognosis of HCC patients. Gene set enrichment analysis further clarified the signalling pathways of the high-risk and low-risk groups constructed based on the IRGs in HCC. Next, we evaluated the correlation between the risk score and the infiltration of immune cells, and finally, we validated the prognostic performance of this model in the GSE14520 dataset. Results A total of 100 immune-related DEGs were significantly associated with the clinical outcomes of patients with HCC. We performed univariate and multivariate least absolute shrinkage and selection operator (Lasso) regression analyses on these genes to construct a prognostic model of seven IRGs (Fatty Acid Binding Protein 6 (FABP6), Microtubule-Associated Protein Tau (MAPT), Baculoviral IAP Repeat Containing 5 (BIRC5), Plexin-A1 (PLXNA1), Secreted Phosphoprotein 1 (SPP1), Stanniocalcin 2 (STC2) and Chondroitin Sulfate Proteoglycan 5 (CSPG5)), which showed better prognostic performance than the tumour/node/metastasis (TNM) staging system. Moreover, we constructed a regulatory network related to transcription factors (TFs) that further unravelled the regulatory mechanisms of these genes. According to the median value of the risk score, the entire TCGA cohort was divided into high-risk and low-risk groups, and the low-risk group had a better overall survival (OS) rate. To predict the OS rate of HCC, we established a gene- and clinical factor-related nomogram. The receiver operating characteristic (ROC) curve, concordance index (C-index) and calibration curve showed that this model had moderate accuracy. The correlation analysis between the risk score and the infiltration of six common types of immune cells showed that the model could reflect the state of the immune microenvironment in HCC tumours. Conclusion Our IRG prognostic model was shown to have value in the monitoring, treatment, and prognostic assessment of HCC patients and could be used as a survival prediction tool in the near future.

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Development and Verification of the Hypoxia- and Immune-Associated Prognostic Signature for Pancreatic Ductal Adenocarcinoma

Frontiers in Immunology ◽

10.3389/fimmu.2021.728062 ◽

2021 ◽

Vol 12 ◽

Author(s):

Dongjie Chen ◽

Hui Huang ◽

Longjun Zang ◽

Wenzhe Gao ◽

Hongwei Zhu ◽

...

Keyword(s):

High Risk ◽

Pancreatic Ductal Adenocarcinoma ◽

Risk Score ◽

Cox Regression ◽

Pearson Correlation ◽

Risk Groups ◽

Low Risk ◽

Ductal Adenocarcinoma ◽

Prognostic Signature ◽

Score Model

We aim to construct a hypoxia- and immune-associated risk score model to predict the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). By unsupervised consensus clustering algorithms, we generate two different hypoxia clusters. Then, we screened out 682 hypoxia-associated and 528 immune-associated PDAC differentially expressed genes (DEGs) of PDAC using Pearson correlation analysis based on the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression project (GTEx) dataset. Seven hypoxia and immune-associated signature genes (S100A16, PPP3CA, SEMA3C, PLAU, IL18, GDF11, and NR0B1) were identified to construct a risk score model using the Univariate Cox regression and the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression, which stratified patients into high- and low-risk groups and were further validated in the GEO and ICGC cohort. Patients in the low-risk group showed superior overall survival (OS) to their high-risk counterparts (p < 0.05). Moreover, it was suggested by multivariate Cox regression that our constructed hypoxia-associated and immune-associated prognosis signature might be used as the independent factor for prognosis prediction (p < 0.001). By CIBERSORT and ESTIMATE algorithms, we discovered that patients in high-risk groups had lower immune score, stromal score, and immune checkpoint expression such as PD-L1, and different immunocyte infiltration states compared with those low-risk patients. The mutation spectrum also differs between high- and low-risk groups. To sum up, our hypoxia- and immune-associated prognostic signature can be used as an approach to stratify the risk of PDAC.

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Immune‐related Long Noncoding RNA Signature for Patients with Cervical Cancer

10.21203/rs.3.rs-49217/v1 ◽

2020 ◽

Author(s):

Jianfeng Zheng ◽

Jinyi Tong ◽

Benben Cao ◽

Xia Zhang ◽

Zheng Niu

Keyword(s):

Cervical Cancer ◽

High Risk ◽

Risk Score ◽

Immune Cell ◽

Risk Group ◽

Risk Groups ◽

Low Risk ◽

Gene Set Enrichment Analysis ◽

Training Set ◽

Score Model

Abstract Background: Cervical cancer (CC) is a common gynecological malignancy for which prognostic and therapeutic biomarkers are urgently needed. The signature based on immune‐related lncRNAs(IRLs) of CC has never been reported. This study aimed to establish an IRL signature for patients with CC.Methods: The RNA-seq dataset was obtained from the TCGA, GEO, and GTEx database. The immune scores（IS）based on single-sample gene set enrichment analysis (ssGSEA) were calculated to identify the IRLs, which were then analyzed using univariate Cox regression analysis to identify significant prognostic IRLs. A risk score model was established to divide patients into low-risk and high-risk groups based on the median risk score of these IRLs. This was then validated by splitting TCGA dataset(n=304) into a training-set(n=152) and a valid-set(n=152). The fraction of 22 immune cell subpopulations was evaluated in each sample to identify the differences between low-risk and high-risk groups. Additionally, a ceRNA network associated with the IRLs was constructed.Results: A cohort of 326 CC and 21 normal tissue samples with corresponding clinical information was included in this study. Twenty-eight IRLs were collected according to the Pearson’s correlation analysis between immune score and lncRNA expression (P < 0.01). Four IRLs (BZRAP1-AS1, EMX2OS, ZNF667-AS1, and CTC-429P9.1) with the most significant prognostic values (P < 0.05) were identified which demonstrated an ability to stratify patients into low-risk and high-risk groups by developing a risk score model. It was observed that patients in the low‐risk group showed longer overall survival (OS) than those in the high‐risk group in the training-set, valid-set, and total-set. The area under the curve (AUC) of the receiver operating characteristic curve (ROC curve) for the four IRLs signature in predicting the one-, two-, and three-year survival rates were larger than 0.65. In addition, the low-risk and high-risk groups displayed different immune statuses in GSEA. These IRLs were also significantly correlated with immune cell infiltration. Conclusions: Our results showed that the IRL signature had a prognostic value for CC. Meanwhile, the specific mechanisms of the four-IRLs in the development of CC were ascertained preliminarily.

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Retrospective Comparative Analysis of POPF Using Fistula Risk Score According to Pancreaticoenterostomy Method

International Surgery ◽

10.9738/intsurg-d-20-00033.1 ◽

2021 ◽

Vol 105 (1-3) ◽

pp. 559-563

Author(s):

Seungmin Lee ◽

Kwang Yeol Paik

Keyword(s):

High Risk ◽

Pancreatic Fistula ◽

Risk Score ◽

Risk Group ◽

Risk Groups ◽

High Risk Group ◽

Postoperative Pancreatic Fistula ◽

Clinical Risk Score ◽

Reconstructive Methods ◽

Fistula Risk Score

Background The aim of this study is to examine whether pancreaticogastrostomy (PG) or pancreaticojejunostomy (PJ) is the better reconstructive method to reduce postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) according to the fistula risk. Methods An institutional database was reviewed for patients undergoing PD between January 2008 and August 2019. A total of 159 patients were stratified into 4 groups according to the Clinical Risk Score-Pancreatic Fistula. POPF according to 4 risk groups was compared between PJ and PG. Results Of the 159 patients, 82 underwent PG (51.6%) and 77 underwent PJ (48.4%) reconstruction. POPF rate was 17.1% (n = 14) in the PG group and 12.9% (n = 10) in the PJ group (P = 0.51). POPF rates were not different in intermediate, low, and negligible risks between 2 reconstructive methods. In the high-risk group (n = 47), there were 4 POPFs (22.2%) in PJ group and 9 (31.0%) in the PG group, respectively (P = 0.74). Conclusion In PD, there was no superior method of reconstruction with regard to POPF, even in high-risk glands.

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An immune-related lncRNA signature as a prognostic immunotherapy target for colon cancer

10.21203/rs.3.rs-35120/v1 ◽

2020 ◽

Author(s):

Bin Wu ◽

Yi Yao ◽

Yi Dong ◽

Si Qi Yang ◽

Deng Jing Zhou ◽

...

Keyword(s):

Colon Cancer ◽

High Risk ◽

Risk Score ◽

Enrichment Analysis ◽

Risk Groups ◽

Low Risk ◽

Gene Set Enrichment Analysis ◽

Risk Scores ◽

Gene Set Enrichment ◽

Immunotherapy Target

Abstract Background：We aimed to investigate an immune-related long non-coding RNA (lncRNA) signature that may be exploited as a potential immunotherapy target in colon cancer. Materials and methods: Colon cancer samples from The Cancer Genome Atlas (TCGA) containing available clinical information and complete genomic mRNA expression data were used in our study. We then constructed immune-related lncRNA co-expression networks to identify the most promising immune-related lncRNAs. According to the risk score developed from screened immune-related lncRNAs, the high-risk and low-risk groups were separated on the basis of the median risk score, which served as the cutoff value. An overall survival analysis was then performed to confirm that the risk score developed from screened immune-related lncRNAs could predict colon cancer prognosis. The prediction reliability was further evaluated in the independent prognostic analysis and receiver operating characteristic curve (ROC). A principal component analysis (PCA) and gene set enrichment analysis (GSEA) were performed for functional annotation. Results: Information for a total of 514 patients was included in our study. After multiplex analysis, 12 immune-related lncRNAs were confirmed as a signature to evaluate the risk scores for each patient with cancer. Patients in the low-risk group exhibited a longer overall survival (OS) than those in the high-risk group. Additionally, the risk scores were an independent factor, and the Area Under Curve (AUC) of ROC for accuracy prediction was 0.726. Moreover, the low-risk and high-risk groups displayed different immune statuses based on principal components and gene set enrichment analysis.Conclusions: Our study suggested that the signature consisting of 12 immune-related lncRNAs can provide an accessible approach to measuring the prognosis of colon cancer and may serve as a valuable antitumor immunotherapy.

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P0357VALIDATION OF THE ANCA RENAL RISK SCORE IN A LONDON COHORT: POTENTIAL IMPACT OF TREATMENT ON PREDICTION OUTCOME

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0357 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

PEK GHE TAN ◽

Jennifer O'Brien ◽

Megan Griffith ◽

Marie Condon ◽

Tom Cairns ◽

...

Keyword(s):

High Risk ◽

Risk Score ◽

Risk Group ◽

Risk Groups ◽

Renal Outcome ◽

Combination Regimen ◽

Renal Survival ◽

Medium Risk ◽

Risk Patients ◽

Potential Impact

Abstract Background and Aims A renal risk score was recently developed to predict the risk of progression to end stage kidney disease (ESKD) in patients with ANCA-associated glomerulonephritis (ANCA-GN). The score defines three risk groups, each with distinct renal survival at 36 months: 68% of high-risk patients reaching ESKD, compared to 26% and 0% in the medium- and low-risk groups, respectively. The majority of patients (101/115) used to define the risk score were treated with IV cyclophosphamide and steroids. At our centre, we employ a combined low-dose IV cyclophosphamide, rituximab and oral corticosteroid induction regimen, with or without plasma exchange (PEX) depending on disease severity, for ANCA-GN. A recent cohort study suggested this combination regimen may lead to better renal survival. We thus hypothesized that choice of remission-induction treatment may affect prediction accuracy of the risk tool. We retrospectively test the validity of the ANCA renal risk score in patients with ANCA-GN treated at our centre. Method All patients with newly diagnosed, biopsy-proven ANCA-GN from 2006-19 were identified from local renal histopathology database. Patients with relapsing ANCA-GN, EGPA, other coexisting GN, or missing data on induction therapy or eventual renal outcome were excluded. ANCA-negative pauci-immune GN was included. Baseline demographics, ANCA serology, initial therapy and parameters in the ANCA risk score (including % normal glomeruli, % tubular atrophy and interstitial fibrosis (TAIF), and estimated glomerular filtration rate were collected. All patients were stratified using the risk tool and Kaplan Meier survival analysis was applied to examine the ESKD prediction. Subgroup analysis was then performed for patients who received the combination regimen of cyclophosphamide and rituximab. Results 178 patients with a median follow up of 44 month were included in the analysis. The median age was 62 years and 82 patients (46%) were female. 94(53%) were MPO-ANCA positive, 66(37%) PR3-ANCA positive, 15 (8%) ANCA-negative, and 3 (2%) were double PR3/MPO-ANCA positive. 148 (83%) patients received the combination regimen, and 45 had concurrent PEX. Total of 37 (21%) patients reached ESKD. 29 (78%) of these, developed ESKD within 36 months of initial diagnosis. Using the risk score, 64(36%), 76(43%) and 38(21%) patients were deemed low-, medium- and high-risk, respectively. Very distinct poor renal survival at 36 months was seen in high-risk group (55% reaching ESKD, p<0.01), but was less apparent between low- (95%) and medium-risk (90%)(p=0.052) (Figure1); In the subgroup of patients treated with combination regimen without concurrent PEX, the high-risk subgroup continues to demonstrate poor renal survival at 36 months (60% ESKD), but renal survival between low- and medium-risk group were comparable (0 and 2% respectively, p=0.57) (Figure 2). Conclusion In our cohort, the ANCA Renal Risk Score reliably predicted rapid ESKD progression at 36-month in high-risk patients, but was less accurate for distinguishing patients with low-and medium-risk. The subgroup analysis suggested combined cyclophosphamide and rituximab therapy may have modified long-term renal outcome especially in the medium-risk cohort, influencing the accuracy of the prediction tool. Large multi-centre cohorts are required to further evaluate the potential impact of treatment on predicting outcome.

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Revalidation of the Flipi Score in the Era of Immunotherapy.

Blood ◽

10.1182/blood.v110.11.4437.4437 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4437-4437

Author(s):

German Stemmelin ◽

Carlos Doti ◽

Claudia Shanley ◽

Jose Ceresetto ◽

Oscar Rabinovich ◽

...

Keyword(s):

Bone Marrow ◽

High Risk ◽

Univariate Analysis ◽

Risk Groups ◽

Marrow Transplant ◽

Intermediate Risk ◽

Significant Difference ◽

The Difference ◽

The One ◽

The Impact

Abstract The FLIPI prognosis score for follicular lymphoma (FL) was developed based on cases diagnosed between 1985 and 1992, and treated with different schemes that did not include rituximab (R). In the present study, we report the evolution of all FL treated in a single institution through the last decade and analize whether FLIPI mantains its effectiveness to identify different risk groups within patients treated with the new therapeutic alternatives available. Material and Methods: We identified sixty two patients with diagnosis of grade I-II-IIIa FL. Patients characteristics: median age 57.5 yr (r, 30–80); 36 males; 63% stages III–IV, and 37% with bone marrow infiltration at the time of diagnosis. Thirty eight percent had a low risk by FLIPI, 34% had an intermediate risk and 27.4% had a high risk. In 19 pts (30.6%) the initial decision was “watch and wait” but 82% received a form of treatment at some point. R was used in 36 pts (58%) with some of the following regimes: chemotherapy (chemo) + R and/or R as consolidation therapy and/or R as monotherapy and/or R as maintenance therapy. Of all prescribed treatments (excluding R as monotherapy and/or maintenance treatment), 52.8% were chemo alone, 20.2% chemo + R, 21.3% radiotherapy and 5.6% received a bone marrow transplant. Results: we considered the analysis of overall survival (OS) the most appropiate approach, since most treatments were seeking the control of the FL, and not the complete remission or cure. The follow up median time was 53.2 months ± 34.8 1SD. The 5-yr OS for the 62 pts was 81.8% ± 11.3 CI 95%. The 5-yr OS for those with a low, intermediate and high risk FLIPI was 100% −5, 84.2% ± 21 and 52% ±26.2, respectively. The difference in 5-yr OS was statistically significant between low and high risk, intermediate and high risk, but failed to prove a significant difference between low and intermediate risk. Among the different risk factors tested in a univariate analysis only age ≥ < 60 yr old demonstrated a significant difference, 60.7% vs 90%, respectively. Conclusions: The 5-yr OS in our series is higher than the one described in the original FLIPI study (Blood2004; 104:1258–65) which was 81.8% vs 71% for the whole group; 90% vs 78.1% for pts <60 yr old; 60.7% vs 57.7% for ≥ 60 yr old; 100% vs 90.6% for low FLIPI and 84.2% vs 77.6% for intermediate FLIPI. The only group that failed to prove an improvement was the high risk FLIPI with 52% vs 52.5%. The impact of novel therapies was more evident in patients with a low or intermediate FLIPI and was even more evident in patients younger than 60 yr old. According to our results, FLIPI maintains its effectiveness in differentiating two risk groups, i.e., low-intermediate vs high. We believe that the OS curves will probably continue to improve as the treatments that are considered today as the most effective ones, were just included in our series in the last three years.

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A Risk Score to Predict CMV Viremia within the First 100 Days after Allogeneic Stem Cell Transplantation Based on Pre-Transplant Parameters

Blood ◽

10.1182/blood.v124.21.3877.3877 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3877-3877

Author(s):

Feras Alfraih ◽

John Kuruvilla ◽

Naheed Alam ◽

Anna Lambie ◽

Vikas Gupta ◽

...

Keyword(s):

Risk Factors ◽

Stem Cell ◽

High Risk ◽

Risk Score ◽

Risk Group ◽

Risk Groups ◽

Low Risk ◽

Cmv Infection ◽

Allogeneic Hsct ◽

Very High

Abstract Introduction: Cytomegalovirus (CMV) is a major infectious complication following allogeneic hematopoietic stem cell transplantation (HSCT). Risk of CMV infection varies between patients and individualized strategies for monitoring and therapy for CMV are needed. In this study, we attempted to establish a clinical score based on patient and transplant characteristics in order to predict the probability for early CMV viremia (CMV-V) within the first 100 days after HSCT. Methods: A total of 548 patients were evaluated after receiving HSCT between 2005 and 2012 at Princess Margaret Cancer Centre. CMV sero-negative recipients with CMV sero-negative donors (R-D-) were excluded. CMV-V was diagnosed in peripheral blood samples obtained on two occasions either by PCR (>200 IU/ml) or antigenemia testing (>2 positive cells/100000). A total of 378 patients were included into the study. Uni- and multivariable analyses were performed to identify risk factors for CMV-V. A weighted score was assigned to each factor based on the odds ratios determined by the multivariable analysis. A total score was calculated for each patient and used for assignment into one of 4 risk categories, the low risk (score 0-1), the intermediate (score 2-3), the high (score 4-5) and the very high (score 6-8). Median age for all patients was 51 years (range 17-71) and 173 (46%) were female. Matched related donors were used for two hundred fifteen patients (57%). Two hundred forty-three patients (64%) were transplanted for myeloid and 108 (29%) for lymphoid malignancies. One hundred thirteen patients (30%) were CMV sero-positive with a negative donor (R+D-) while 191 (51%) were recipient and donor CMV sero-positivity (R+D+). Graft versus host disease (GVHD) prophylaxis included CSA/MMF (n=200, 52%), and CSA/MTX (n=178, 48%). Myeloablative conditioning regimens were administered to 220 patients (58%), 158 patients (42%) were treated with a reduced intensity regimen. Three hundred-thirty seven patients (89%) received peripheral blood stem cells as a stem cell source. In vivo T cell depletion (TCD) with alemtuzumab was used in 138 (37%). Results: CMV-V occurred in 246 (64%) patients by day 100 post HSCT. The impact of patient and HSCT characteristics on the risk of CMV-V was assessed by multivariable analysis. The significant factors were CMV sero-status R+D- and R+D+, TCD, GVHD prophylaxis with MMF administration of myeloablative preparative regimens (Table 1). Table 1. Multivariate analysis for risk factors of CMV infection following allogeneic HSCT Table 1. Multivariate analysis for risk factors of CMV infection following allogeneic HSCT CMV-V rates on the 4 new risk categories amounted to 93% in the very high-risk, 78% in high-risk, 41% in intermediate-risk and 11% in low-risk group (Fig 1). The risk score was also predictive for the occurrence of multiple CMV-V reactivations with rates of 71%, 45%, 19% and 4% for the very high, high, intermediate and low-risk groups, respectively. The overall survival (OS) rate at 2 years was 33%(n=56) in the very high-risk group compared to 50% in other-risk groups (n=147) (P=0.01) (Fig 2). Non-relapse mortality (NRM) was 53% in the very high-risk versus 33% in other-risk groups (P<0.001). However, there was no difference on cumulative incidence of relapse between the groups (P=0.3). The cumulative incidence of grades 1-4 acute GVHD, grades 2-4, grades 3-4 at day 120 and overall chronic GVHD at 2 years was 68%, 47%, 25% and 39% in very high-risk group versus 65%, 52%, 21% and 52% in other-risk groups, suggesting slightly lower incidence of chronic GVHD in very high-risk vs other-risk groups. Conclusion: We present a new clinical scoring system to stratify the risk of early CMV viremia after allogeneic HSCT based on patients and HSCT characteristics. Identifying the risk for each patient would facilitate decision making with respect to strategies including CMV prophylaxis, pre-emptive treatment or inclusion into clinical trials, as well directing the CMV monitoring policy post-transplant. In addition, the risk score was associated with higher risk of overall mortality and NRM in the very high-risk versus other-risk groups. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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