Prediction of Survival in Patients with Myelodysplastic Syndrome According to WHO Classification-Based Prognostic Scoring System (WPSS).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4617-4617
Author(s):  
Jun Ho Jang ◽  
Kihyun Kim ◽  
Chul W. Jung ◽  
Keon Woo Park
Keyword(s):  
High Risk ◽  
Scoring System ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Risk Scores ◽  
The Mean ◽  
Very High

Abstract Background Based upon the classification of FAB criteria, International Prognostic Scoring System(IPSS) has been a standard prognostic model to predict survival and progression in MDS. In 2000, the WHO has formulated a new classification of myelodysplastic syndrome(MDS). The aim of this study was to evaluate the prognostic value of WHO classification-based prognostic scoring system(WPSS) in MDS. Patients and methods One hundred forty-nine patients who were diagnosed as having de novo MDS at the Division of Hematology-Oncology, Samsung medical center, Seoul, Korea, between Dec. 1994 and Feb. 2007, were evaluated retrospectively for clinical and hamatologic features at diagnosis, transfusion dependence, overall survival(OS), and progression to leukemia(LFS). Risk group stratifications in MDS patients were done according to IPSS and WPSS. Results 18 patients(12.1%), 93 patients (62.4%), 29 patients(29%) and 9 patients(6%) had IPSS risk scores of low, intermediate-1(Int-1), intermediate-2(Int-2) and high, respectively. According to WPSS risk scores, 8 patients(5.4%), 30 patients(20.1%), 41 patients(27.5%), 57 patients(38.3%) and 13 patients(8.7%) were classified to very low, low, intermediate, high and very high risk group, respectively. In IPSS, median OSs of low, Int-1, Int-2 and high subgroup were 65.2, 32.9, 14.3 and 9.1 months respectively (p<0.001). According to WPSS, median OSs of very low, low, intermediate, high and very high risk subgroup were not reached, 55.4, 27.4, 19.0 and 6.2 months respectively (p<0.001). Between subgroups classified according to WPSS, significant differences in OS were noted in low vs. intermediate risk group (p=0.047), in intermediate vs. high risk group (p=0.046) and in high vs. very high risk group(p=0.003) but statistically not significant difference in OS was observed between very low and low risk group (p=0.08). The mean and median OS of the lowest risk group(low risk) in IPSS are 65.33 and 55.43 months, respectively. The mean and median OS of the lowest risk group(very low risk) in WPSS are 102.8 months and not reached, respectively. Conclusion These data show that WPSS with five risk groups might provide more refined prognostic stratifications of MDS than IPSS with four risk groups. Especially, new prognostic system appears to discriminate a subset of patients with very low risk, who could have long term survival.

MD Anderson Scoring System (MDACC) Predicts Outcomes After Hematopoietic Stem Cell Transplantation (HSCT) Better Than Other Prognostic Classifications In MDS

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3340-3340
Author(s):  
Piyanuch Kongtim ◽  
Uday R Popat ◽  
Marcos de Lima ◽  
Guillermo Garcia-Manero ◽  
Elias J. Jabbour ◽  
...  
Keyword(s):  
High Risk ◽  
Scoring System ◽  
Risk Group ◽  
Univariate Analysis ◽  
Scoring Systems ◽  
Risk Groups ◽  
High Risk Group ◽  
Risk Scores ◽  
Hematopoietic Stem ◽  
Very High

Abstract MDS is a heterogeneous group of hematopoietic stem cell disorders. Various prognostic models have been established to categorize patients with MDS including the International Prognostic Scoring System (IPSS), the Revised-IPSS (r-IPSS) and MDACC Scoring System. In this analysis, we compared those three classification schemas for their outcome predictability after HSCT. We analyzed 291 MDS patients with a median age of 55 (interquartile range (IQR) 47-60.7 years) who underwent HSCT between January 2001 and December 2011. Histology by WHO classification included RA/RARS 48 (16.5%), RCMD 28 (9.6%), RAEB-1 59 (20.2%), RAEB-2 63 (21.7%), MDS unclassified 67 (23%), and CMML 26 (9%). Of 291, 117 patients (40.2%) had therapy related MDS (t-MDS). Conditioning regimen was myeloablative in 201 patients (69.1%) and reduced intensity in 90 patients (30.9%). Donors were matched related (MRD), matched unrelated (MUD), mismatched (MMD) in 131 (45%), 114 (39.2%) and 46 (15.8%) patients respectively. Risk categorization was performed by IPSS, r-IPSS and MDACC scoring systems at the time of diagnosis. IPSS, r-IPSS and MDACC scoring systems could be assessed in 239 (82.1%), 241 (82.8%) and 231 (79.4%) patients respectively. The median follow up time of 109 survivors was 45 months. The median time from diagnosis to HSCT was 7.3 months (IQR 4.6-12.4 months). Three-year overall survival (OS) was 38.1% (95%CI 32.3-43.9) with 3-year event free survival (EFS) of 34.2% (95%CI 28.4-40). Cumulative relapse incidence (RI) at 3-year was 28.8% (95%CI 23.3-34.5). Cumulative incidence of treatment related mortality (TRM) at 3 year post-transplant was 27.9% (95%CI 22.6-33.6). In univariate analysis, IPSS and r-IPSS were able to differentiate 2 risk groups for OS and EFS. High risk group per IPSS and very high risk group per r-IPSS had lower OS with hazard ratio (HR) of 2.4 to 3.1, lower EFS with HR of 2.2 to 2.7. While IPSS could not predict RI, very high risk group by r-IPSS had higher RI with HR of 3.6 compared with lower risk groups. Both IPSS and r-IPSS did not identify different risk groups for TRM. On the other hand, MDACC scoring system was able to identify 4 different risk groups for EFS and OS in univariate analysis. Three-year OS was 68%, 46.1%, 30.3% and 11.4% for patients with MDACC risk score of 0-4, 5-6, 7-8 and ≥9 respectively (p<0.001) (figure1). Three-year EFS with MDACC risk score of 0-4, 5-6, 7-8 and ≥9 was 61.7%, 40.8%, 28.1% and 7.4% respectively (p<0.001). For RI and TRM, only MDACC risk scores of ≥9 was associated with poor outcomes with 3-year RI of 38.9% and 3-year TRM of 41.7% compared with 13.3% and 15.5% in risk scores of 0-4 (p=0.01 and p=0.01 respectively). In multivariate analysis, MDACC score, matched unrelated and mismatched donors were associated with inferior OS (table1). As a summary, MDACC risk scoring system for MDS better differentiates prognostic groups than IPSS or r-IPSS. Considering the high frequency of t-MDS among transplanted MDS patients, we propose that MDACC scoring system should be used for prognostic classification for hematopoietic transplantation. Disclosures: No relevant conflicts of interest to declare.

The Utility Of Newer Risk Models In Predicting Outcomes Of Patients (pts) With Higher-Risk (HR) Myelodysplastic Syndromes (MDS) Treated With Azactidine (aza)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2771-2771
Author(s):  
Amer M. Zeidan ◽  
Najla H Al Ali ◽  
Mohamed A. Kharfan-Dabaja ◽  
Eric Padron ◽  
Ling Zhang ◽  
...  
Keyword(s):  
High Risk ◽  
Scoring System ◽  
Research Funding ◽  
Goodness Of Fit ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Information Criteria ◽  
Prognostic Groups ◽  
Very High

Abstract Background While aza is the only drug shown to prolong survival in MDS, only half of aza-treated pts achieve objective responses (10-20% complete remission), and 4-6 months might be needed before a response is seen. Therefore the ability to select pts with high and low likelihoods of benefit from aza therapy is a clinical and a research priority. No clinical or laboratory parameter consistently predicts response or survival with aza therapy. A French prognostic scoring system (FPSS) was proposed to predict survival among aza-treated pts with HR-MDS. We sought to compare the relative prognostic discriminatory power of the FPSS with that of the revised IPSS (IPSS-R) and the global MD Anderson prognostic scoring system (MDAPSS) in a large cohort of aza-treated pts with IPSS HR-MDS. Methods The MDS database at Moffitt Cancer Center (MCC) was used to identify patients with HR-MDS (International Prognostic Scoring System [IPSS] intermediate-2 [INT-2] and high-risk) who received aza therapy. Kaplan-Meier curves were used to depict survivals, and the log-rank test was used to compare median overall survival (OS). Akaike information criteria (AIC) were used to assess the relative goodness of fit of the models. Results We identified 259 patients HR-MDS (74.1% with INT-2 and 25.9% with high IPSS) treated with aza at the MCC. The median duration of follow up since diagnosis was 53 months (M) (95% confidence interval [CI], 49-59 M). The median number of aza cycles was 5 (range 1-72), with 75% of pts receiving 4 cycles of therapy or more. The median time from diagnosis to aza initiation was 1.5 M. The median OS for the entire cohort was 19 M (95%CI, 16-22 M), 64% of pts were males, 91% were white, 80% were older than 60 years, and 25% had therapy-related MDS. For the IPSS, the median OS was 23.5 M (CI, 18.4-28.6 M) for INT-2 and 15.9 M (CI, 13.6-18.2 M) for high-risk group (P=0.004). For the FPSS, the median OS was 29.5 M (CI, 14.1-44.9 M) for low risk (LR), 21.1 M (CI, 16.4-26.0 M) for intermediate risk (IR), and 14.1 M (CI, 8.7-19.5 M) for HR (P=0.001). For the MDAPSS the median OS was not reached (NR) for low, 53.5 M (CI, 37.5-69.4 M) for INT-1, 29.5 M (CI, 18.3-40.6 M) for INT-2, and 16.1 M (CI, 14.5-17.7 M) for high risk groups (P<0.0001). For the IPSS-R, the median OS 40.6 M (CI, 22.8-58.4 M) for low, 44.7 M (CI, 25.0-64.4 M) for INT, 23.5 M (CI, 20.3-26.8 M) for high, and 15.2 M (CI, 13.7-16.8 M) for very-high risk groups (P<0.0001). Scores generated using AIC to assess the relative goodness of fit (lower is better) were 1453 (IPSS-R), 1480 (MDAPSS), 1512 (FPSS), and 1522 (IPSS). The IPSS could not refine any of the other models. All three newer models refined IPSS INT-2 but not IPSS high-risk. The IPSS did not refine any of the newer models. The MDAPSS refined the FPSS LR and IR and the IPSS-R high and very-high groups. The FPSS refined IPSS-R very high risk group but not the not the MDAPSS. The R-IPSS did not refine the MDAPSS or the FPSS. Response rates were not statically significantly different within the prognostic groups in any of the scoring systems. Conclusions The IPSS-R, MDAPSS, and the FPSS all functioned well to separate aza-treated pts with IPSS HR-MDS into prognostic groups with different survivals, but the IPSS-R and MDAPSS appear superior to the FPSS. None of the prognostic systems predicted response to aza therapy. HR-MDS patients with poor projected survival with aza therapy might be considered for experimental approaches. Disclosures: Off Label Use: entinostat for MDS. Lancet:Celgene: Research Funding. List:Celgene: Research Funding. Komrokji:Celgene: Research Funding, Speakers Bureau.

scholarly journals Sernbo score predicts survival after intracapsular hip fracture in the elderly

2013 ◽  
Vol 95 (1) ◽  
pp. 29-33 ◽  
Author(s):  
EJC Dawe ◽  
E Lindisfarne ◽  
T Singh ◽  
I McFadyen ◽  
P Stott
Keyword(s):  
Hip Fracture ◽  
High Risk ◽  
Risk Group ◽  
Characteristic Curve ◽  
Social Situation ◽  
High Risk Group ◽  
Low Risk ◽  
Risk Of Death ◽  
Intracapsular Hip Fracture ◽  
The Mean

Introduction The Sernbo score uses four factors (age, social situation, mobility and mental state) to divide patients into a high-risk and a low-risk group. This study sought to assess the use of the Sernbo score in predicting mortality after an intracapsular hip fracture. Methods A total of 259 patients with displaced intracapsular hip fractures were included in the study. Data from prospectively generated databases provided 22 descriptive variables for each patient. These included operative management, blood tests and co-mobidities. Multivariate analysis was used to identify significant predictors of mortality. Results The mean patient age was 85 years and the mean follow-up duration was 1.5 years. The one-year survival rate was 92% (±0.03) in the low-risk group and 65% (±0.046) in the high-risk group. Four variables predicted mortality: Sernbo score >15 (p=0.0023), blood creatinine (p=0.0026), ASA (American Society of Anaesthesiologists) grade >3 (p=0.0038) and non-operative treatment (p=0.0377). Receiver operating characteristic curve analysis showed the Sernbo score as the only predictor of 30-day mortality (area under curve 0.71 [0.65–0.76]). The score had a sensitivity of 92% and a specificity of 51% for prediction of death at 30 days. Conclusions The Sernbo score identifies patients at high risk of death in the 30 days following injury. This very simple score could be used to direct extra early multidisciplinary input to high-risk patients on admission with an intracapsular hip fracture.

scholarly journals MO048MULTICENTRE PROSPECTIVE VALIDATION OF THE URINARY PEPTIDOME-BASED CLASSIFIER CKD273 AS A PREDICTOR OF RENAL FUNCTION DECLINE IN SUBJECTS WITH TYPE 2 DIABETES

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Morten Lindhardt ◽  
Nete Tofte ◽  
Gemma Currie ◽  
Marie Frimodt-Moeller ◽  
Heiko Von der Leyen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Renal Function ◽  
High Risk ◽  
Risk Group ◽  
Cox Model ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Renal Function Decline

Abstract Background and Aims In the PRIORITY study, it was recently demonstrated that the urinary peptidome-based classifier CKD273 was associated with increased risk for progression to microalbuminuria. As a prespecified secondary outcome, we aim to evaluate the classifier CKD273 as a determinant of relative reductions in eGFR (CKD-EPI) of 30% and 40% from baseline, at one timepoint without requirements of confirmation. Method The ‘Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria trial’ (PRIORITY) is the first prospective observational study to evaluate the early detection of diabetic kidney disease in subjects with type 2 diabetes (T2D) and normoalbuminuria using the CKD273 classifier. Setting 1775 subjects from 15 European sites with a mean follow-up time of 2.6 years (minimum of 7 days and a maximum of 4.3 years). Patients Subjects with T2D, normoalbuminuria and estimated glomerular filtration rate (eGFR) ≥ 45 ml/min/1.73m2. Participants were stratified into high- or low-risk groups based on their CKD273 score in a urine sample at screening (high-risk defined as score &gt; 0.154). Results In total, 12 % (n = 216) of the subjects had a high-risk proteomic pattern. Mean (SD) baseline eGFR was 88 (15) ml/min/1.73m2 in the low-risk group and 81 (17) ml/min/1.73m2 in the high-risk group (p &lt; 0.01). Baseline median (interquartile range) urinary albumin to creatinine ratio (UACR) was 5 (3-8) mg/g and 7 (4-12) mg/g in the low-risk and high-risk groups, respectively (p &lt; 0.01). A 30 % reduction in eGFR from baseline was seen in 42 (19.4 %) subjects in the high-risk group as compared to 62 (3.9 %) in the low-risk group (p &lt; 0.0001). In an unadjusted Cox-model the hazard ratio (HR) for the high-risk group was 5.7, 95 % confidence interval (CI) (3.9 to 8.5; p&lt;0.0001). After adjustment for baseline eGFR and UACR, the HR was 5.2, 95 % CI (3.4 to 7.8; p&lt;0.0001). A 40 % reduction in eGFR was seen in 15 (6.9 %) subjects in the high-risk group whereas 22 (1.4 %) in the low-risk group developed this endpoint (p&lt;0.0001). In an unadjusted Cox-model the HR for the high-risk group was 5.0, 95 % CI (2.6 to 9.6; p&lt;0.0001). After adjustment for baseline eGFR and UACR, the HR was 4.8, 95 % CI (2.4 to 9.7; p&lt;0.0001). Conclusion In normoalbuminuric subjects with T2D, the urinary proteomic classifier CKD273 predicts renal function decline of 30 % and 40 %, independent of baseline eGFR and albuminuria.

scholarly journals Immune-Related Four-lncRNA Signature for Patients with Cervical Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Jianfeng Zheng ◽  
Benben Cao ◽  
Xia Zhang ◽  
Zheng Niu ◽  
Jinyi Tong
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Immune Cell ◽  
Risk Group ◽  
Pearson Correlation ◽  
Characteristic Curve ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Gynecological Malignancy

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 is aimed at establishing an IRL signature for patients with CC. 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 correlation analysis between the 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 the 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-IRL signature in predicting the one-, two-, and three-year survival rates was 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. 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.

Validation of a Novel Tissue Array Based Classification of Multiple Myeloma (MM).

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1671-1671
Author(s):  
Nizar J Bahlis ◽  
Alex Klimowicz ◽  
Paola Neri ◽  
Anthony Magliocco ◽  
Douglas A. Stewart ◽  
...  
Keyword(s):  
High Risk ◽  
Validation Cohort ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Protein Array ◽  
Immunoperoxidase Staining ◽  
Initial Testing ◽  
Independent Validation

Abstract Background: Gene expression profiling molecular classification of MM was proven to be an independent predictor of survival post autologous stem cell transplant (ASCT); however it had limited clinical applicability due to its complex methodology and high costs. We have previously reported the results of a protein-array based classification of MM in an initial testing cohort and concluded that positive immunoperoxidase staining for FGFR3, Cyclin B2 or Integrin beta7 correlates with a shortened survival post ASCT (Bahlis et al. Blood2007:110:449a). We now report on the results of this TMA classification in a larger and independent validation cohort. Methods: Immunoperoxidase staining for Cyclins B1, B2, D1, D2 and D3, FGFR3, PAX5 and Integrin beta 7 were previously validated in our initial testing cohort (n=52). Further analysis of our initial testing cohort identified 3 risk groups: positive expression of FGFR3 or Integrin beta 7 defined as “High risk”, positive Cyclin B2 (in the absence of FGFR3 or Integrin beta 7) as “Intermediate risk” and the lack of expression of any of these biomarkers defined as “Low risk”. In order to confirm the predictive value of our proposed protein-array classification, these immunohistochemical (IHC) stains were performed on the bone marrow biopsies of a larger and independent validation cohort of 79 newly diagnosed MM patients uniformly treated with a dexamethasone based regimen followed by ASCT. The clinical parameters, response criteria and survival outcomes (TTP and OS) of this validation cohort were defined according to the international uniform response criteria. For IHC analysis two pathologists who were blinded with regards to the clinical outcome of these patients scored the cases independently as positive or negative. Discordance in their scoring was seen in 20/79 (25.7%) with a consensus scoring reassigned to all of these cases. The Kaplan-Meier method was used to estimate OS and TTP. Multivariate analysis was performed using the Cox regression method. Figure Figure Results: 79 patients were included in this validation cohort, the median age was 54.4 yrs (27.9–71), 23.7% had ISS stage III, median beta 2-microglobulin was 3.29 mg/L (1.16–37.5). Del13q and t(4;14) were detected by FISH in 35.6% and 13.6% of patients, respectively. Post ASCT, 68% achieved a CR or VGPR with an overall median TTP and OS of 2.29 years (CI 1.84–2.73) and 5.74 years (CI 4.98–6.51) respectively. Expression of FGFR3 was detected in 7.6% of the patients, cyclin B2 in 58.2% and integrin-beta7 in 17.7%. In univariate analysis expression of FGFR3 was associated with a significantly shorter TTP (P=0.011) but not OS (P=0.114). Similarly integrin-beta7 predicted for a shorter TTP (P=0.008) but not OS (P=0.570). Cyclin B2 also predicted for worse TTP (P=0.047) but not OS (P=0.098), whereas the expression of cyclins D1, D2, D3 and PAX5 did not affect survival. Based on our testing cohort definition of risk groups, 18/79 (22.8%) were considered as “High risk” with significantly shorter TTP 0.93 years (CI 0.74–1.12) compared to 2.29 years (CI 1.88–2.69) and 3.35 years (CI 2.51–4.19) for the “Intermediate” (34/79; 43%) and “Low” (27/79; 34.2%) risk groups respectively (P=0.002). The 5-years estimates for OS was 57.1% for the High-risk group compared to 66.3% and 71.6% for the Intermediate and Low risk group respectively (P=0.258). Multivariate analysis was performed using ISS, del13q and the TMA risk group classification as variables. The TMA classification and del 13q were the only independent predictors of TTP with the high-risk group having 3.4 fold greater risk of relapse (P=0.001). Conclusion: We have validated our protein array based classification of Multiple Myeloma and confirmed its survival predictive value post ASCT. MM patients with the High-risk signature should be spared the toxicity of ASCT and considered instead for other frontline novel therapeutic agents.

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

Blood ◽  
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.

Chemotherapy-associated thrombosis in cancer outpatients: Risk factors and decision making of a prophylactic approach.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20647-e20647
Author(s):  
Martina Torchio ◽  
Benvenuto Franceschetti ◽  
Carla Cavali ◽  
Sonia Zanirato ◽  
Angelo Olgiati ◽  
...  
Keyword(s):  
Risk Factors ◽  
Decision Making ◽  
High Risk ◽  
Scoring System ◽  
Risk Group ◽  
Venous Catheter ◽  
Risk Groups ◽  
High Risk Group ◽  
Factors Analysis ◽  
Negative Predictor

e20647 Background: Venous thromboembolism (VTE), is a negative predictor of survival in pts with advanced cancer. International guidelines don’t recommend routine prophlaxis but suggest to consider pts, undergoing chemotherapy (CT), with high risk of VTE. Many clinical risk factors for cancer-associated VTE have been evaluated in a 5 parameter-based (body mass index, platelet and leucocyte counts, hemoglobin value and tumor site) scoring system, the Khorana score, utilized to indicate a prophylactic approach. We prospectively applied this score in cancer outpts beginning CT and an implementation based on 6 addictional factors analysis (sex, age, central venous catheter, CT-agents, antiangiogenetic drugs, erithropoiesis stimulating agent) to evaluate their impact in pts assignment into risk groups. Methods: We studied adult pts, followed at our Department from August 2011 to December 2012, with advanced cancers (breast, NSCLC, colorectal, pancreatic/gastric, urogenital, LNH, Hodgkin's disease, HD, and MM), receiving a first or second line standard CT. We stratified pts into three risk groups (score 0= low; score 1-2=intermediate; score 3-4-5=high) considering both the Khorana scoring system and its implementation. Results: We analyzed 169 pts (103F/66M, median age 62.3, range 35-80 yrs), pt population included: 38 breast, 32 colorectal, 31 LNH, HD and MM, 27 urogenital, 22 NSCLC and 19 pancreatic/gastric. With the Khorana score 49 pts were assigned to the low risk, 87 pts to the intermediate risk (57 with score=1, 28 with score=2), 16 pts (9.4%) to the high risk group (9 with score=3, 4 with score=4, 3 with score=5). When we considered 11 parameters 37 pts (21.8%) were assigned to the high risk group. Conclusions: A more comprehensive quantification of VTE risk, also considering new independent factors, is mandatory for a correct decision making of an antithrombotic-prophylactic approach.

The Glasgow whipple risk score to predict pancreas-specific complications after pancreaticoduodenectomy.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 394-394
Author(s):  
Lavanniya Kumar Palani Velu ◽  
Vishnuvardhan Chandrabalan ◽  
Ross Carter ◽  
Colin McKay ◽  
Donald McMillan ◽  
...  
Keyword(s):  
High Risk ◽  
Serum Amylase ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Prolonged Stay ◽  
Increased Risk ◽  
Clinically Significant ◽  
Serum Crp

394 Background: Pancreas-specific complications (PSC), comprising postoperative pancreatic fistula, post-pancreatectomy haemorrhage, and intra-abdominal collections, are drivers of morbidity following pancreaticoduodenectomy (PD). Intra-operatively derived pancreatic gland texture is a major determinant of postoperative PSC. We have previously demonstrated that a postoperative day 0 (PoD0) serum amylase ≥ 130 IU/L is an objective surrogate of pancreatic texture, and is associated with PSC. We sought to refine the PSC risk prediction model by including serial measurements of serum C-reactive protein (CRP). Methods: 230 consecutive patients undergoing PD between 2008 and 2014 were included in the study. Routine serum investigations, including amylase and CRP were performed from the pre-operative day. Receiver operating characteristic (ROC) curve analysis was used to identify a threshold value of serum CRP associated with clinically significant PSC. Results: 95 (41.3%) patients experienced a clinically significant PSC. ROC analysis identified post-operative day 2 (PoD2) serum CRP of 180 mg/L as the optimal threshold (P=0.005) associated with clinically significant PSC, a prolonged stay in critical care (P =0.032), and a relaparotomy (P = 0.045). Patients with a PoD0 serum amylase ≥ 130 IU/L who then developed a PoD2 serum CRP ≥ 180 mg/L had a higher incidence of postoperative complications. Patients were categorised into high, intermediate and low risk groups based on PoD0 serum amylase and PoD2 serum CRP. Patients in the high risk group (PoD0 serum amylase ≥ 130 IU/L and PoD2 serum CRP ≥ 180 mg/l) had significantly higher incidence of PSC, a return to theatre, prolonged lengths stay (all P≤ 0.05) and a four-fold increase in perioperative mortality compared patients in the intermediate and low risk groups (7 deaths in the high risk group versus 2 and nil in the intermediate and low risk groups respectively). Conclusions: A high risk profile, defined as PoD0 serum amylase ≥ 130 IU/L and PoD2 serum CRP ≥ 180 mg/l, should raise the clinician’s awareness of the increased risk of clinically significant PSC and a complicated postoperative course following pancreaticoduodenectomy.

scholarly journals Validation of Clinical Prognostic Models and Integration of Genetic Biomarkers of Drug Resistance in CLL Patients Treated with Ibrutinib

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 186-186 ◽  
Author(s):  
Inhye E. Ahn ◽  
Xin Tian ◽  
Maher Albitar ◽  
Sarah E. M. Herman ◽  
Erika M. Cook ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Prognostic Models ◽  
Discovery Cohort ◽  
Treatment Naïve ◽  
Equity Ownership

Abstract Introduction: We previously reported a prognostic scoring system in CLL using pre-treatment factors in patients treated with ibrutinib [Ahn et al, 2016 ASH Annual Meeting]. Here we present long-term follow-up results and validation of the prognostic models in a large independent cohort of patients. We also determine the incidence of resistance-conferring mutations in BTK and PLCG2 genes in different clinical risk groups. Methods and Patients: The discovery cohort comprised 84 CLL patients on a phase II study with either TP53 aberration (deletion 17p or TP53 mutation) or age ≥65 years (NCT01500733). The validation cohort comprised 607 patients pooled from four phase II and III studies for ibrutinib in treatment-naïve or relapsed/refractory CLL (NCT01105247; NCT01578707; NCT01722487; NCT01744691). All patients received single-agent ibrutinib 420mg once daily. We used Cox regression models to identify independent predictors of PFS, Kaplan-Meier method to estimate probabilities of PFS, log-rank test to compare PFS, and Cochran-Armitage trend test to compare the incidence of mutation among subgroups. We used R version 3.5.0 or SAS® version 9.3 for statistical analyses. For biomarker correlation, we tested cellular DNA or cell-free DNA collected from patients in the discovery cohort with the targeted sequencing of BTK and PLCG2 genes. Result: At a median follow-up of 5.2 years, 28 (33.3%) of 84 patients in the discovery cohort progressed or died. 52 (61.9%) patients had treatment-naïve CLL. Independent factors of PFS on univariate analysis were; TP53 aberration, prior treatment, and β-2 microglobulin (B2M) >4mg/L (P<0.05 for all tests). Unmutated IGHV and advanced Rai stage (III/IV) showed a trend toward inferior outcome without reaching statistical significance. Because higher levels of B2M were associated with relapsed/refractory CLL, we performed two multivariate Cox regression models to assess B2M and prior treatment status separately. Risk groups were determined by the presence of TP53 aberration, advanced Rai stage, and B2M >4mg/L for Model 1, and TP53 aberration, advanced Rai stage, and relapsed/refractory CLL for Model 2 (Table 1). The high-risk group had all three adverse risk factors; the intermediate-risk group had two risk factors; and the low-risk group, none or one. The median PFS of the high-risk group was 38.9 months for Model 1 and 38.4 months for Model 2, and was significantly shorter than those of intermediate and low-risk groups. In the validation cohort, 254 (41.8%) of 607 patients progressed or died at a median follow-up of 4.2 years. 167 (27.5%) patients had treatment-naïve CLL. Both models showed statistically significant differences in PFS by risk groups (Table 1). For the high-risk group, 4-year PFS was 30.2% in Model 1 and 30.5% in Model 2, which were inferior to those of intermediate (53.4 and 52.4%) and low-risk groups (68.7 and 73.7%). Model 1 classified 20% of patients and Model 2 classified 28% of patients to the high-risk group. BTK and PLCG2 mutations are common genetic drivers of ibrutinib resistance in CLL. To determine whether the incidence of these mutations correlates with prognostic risk groups, we performed targeted sequencing of BTK and PLCG2 of samples collected from patients in the discovery cohort. We used cell-free DNA for patients who received long-term ibrutinib (≥3 years) and had low circulating tumor burden, and cellular DNA, for samples collected within 3 years on ibrutinib or at progression. Of 84 patients, 69 (82.1%) were tested at least once, and 37 (44.0%) were tested at least twice. The frequency of testing was similar across the risk groups by two models (P>0.05). The cumulative incidences of mutations at 5 years in the low-, intermediate-, and high-risk groups were: 21.4%, 44.8% and 50%, respectively, by Model 1 (P=0.02); and 22.6%, 41.4% and 66.7%, respectively, by Model 2 (P=0.01). Conclusion: We developed and validated prognostic models to predict the risk of disease progression or death in CLL patients treated with ibrutinib. Risk groups classified by three commonly available pre-treatment factors showed statistically significant differences in PFS. The clinically-defined high-risk disease was linked to higher propensity to develop clonal evolution with BTK and/or PLCG2 mutations, which heralded ibrutinib resistance. Disclosures Albitar: Neogenomics Laboratories: Employment. Ma:Neogenomics Laboratories: Employment. Ipe:Pharmacyclics, an AbbVie Company: Employment, Other: Travel; AbbVie: Equity Ownership. Tsao:Pharmacyclics LLC, an AbbVie Company: Employment. Cheng:Pharmacyclics LLC, an AbbVie Company: Employment. Dean:CTI BioPharma Corp.: Employment, Equity Ownership; Pharmacyclics LLC, an AbbVie Company: Employment, Equity Ownership. Wiestner:Pharmacyclics LLC, an AbbVie Company: Research Funding.

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