End-of-radiation PSA as a novel prognostic factor in patients undergoing definitive radiation for prostate cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 68-68 ◽  
Author(s):  
Phuoc T. Tran ◽  
Amol Narang ◽  
Ashwin Ram ◽  
Scott P. Robertson ◽  
Pei He ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Multivariate Analysis ◽  
High Risk ◽  
Low Risk ◽  
Risk Level ◽  
Treatment Intensification ◽  
Entire Cohort ◽  
Kaplan Meier ◽  
Risk Patients ◽  
Poor Outcomes

68 Background: In patients with localized prostate cancer undergoing radiation therapy (RT) +/- androgen deprivation therapy (ADT), an end of radiation (EOR) PSA obtained during the last week of RT may serve as an early post-treatment predictor of poor outcomes and identify patients in whom to pursue treatment intensification or novel therapies. Methods: We reviewed an IRB-monitored, prospectively acquired database of patients with prostate cancer treated with definitive RT at our institution from 1993-2007 (n=890). Patients with an available EOR PSA were divided into two cohorts and analyzed separately based on inclusion of ADT into the treatment regimen. EOR PSA thresholds of 0.5 ng/mL and 1.0 ng/mL were explored. Multivariate analysis was performed to determine prognostic factors for biochemical failure-free survival (BFFS, Phoenix criteria) and overall survival (OS). Kaplan-Meier survival curves were constructed, with stratification by EOR PSA thresholds. Results: Median age was 69 years, with an even distribution of NCCN low risk (33.5%), intermediate risk (34.0%), and high risk (32.5%) patients. Median RT dose was 7020 cGy, and 54.5% were treated with ADT. Median follow-up of the entire cohort was 11.7 yrs. EOR PSA level was available for the majority of patients (77.5%). On multivariate analysis, EOR PSA >0.5 ng/mL was significantly associated with worse BFFS (p<0.0001) and OS (p<0.0001). In the subset of patients undergoing RT with ADT for NCCN intermediate/high risk disease, 5 yr BFFS was more disparate based an EOR PSA threshold of 0.5 ng/mL (5 yr BFFS: 87.3% vs. 41.1%, p<0.001), than initial NCCN risk level (5 yr BFFS: 88.7% vs. 76.9%, p=0.038). In NCCN low risk patients undergoing definitive RT alone, an EOR PSA threshold of 1.0 ng/mL was significantly prognostic of outcome (5 yr BFFS: 100.0% vs. 88.6%, p=0.024). Conclusions: For NCCN intermediate/high risk patients undergoing RT with ADT, EOR PSA >0.5 ng/mL may represent a better surrogate for poor outcomes than initial risk group. In addition, NCCN low risk patients undergoing RT alone who obtained an EOR PSA ≤1.0 ng/mL experienced excellent BFFS. Prospective evaluation of the utility of EOR PSA should be explored.

scholarly journals Identification of A Novel Six Autophagy-Related Genes Signature for The Prognostic and A miRNA-Related Autophagy Predictor for Anti-PD-1 Therapy Responses in Prostate Cancer

2020 ◽  
Author(s):  
Lei Wu ◽  
Guojun Yue ◽  
Wen Quan ◽  
Qiong Luo ◽  
Dongxu Peng ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Regression Model ◽  
Risk Group ◽  
Low Risk ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Prognostic Signature ◽  
Potential Biomarker ◽  
Risk Patients

Abstract Background: Autophagy is a highly conserved homeostatic process in the human body that is responsible for the elimination of aggregated proteins and damaged organelles. Several autophagy-related genes (ARGs) contribute to the process of tumorigenesis and metastasis of prostate cancer (PCa). Also, miRNAs have been proven to modulate autophagy by targeting some ARGs. However, their potential role in PCa still remains unclear.Methods: An univariate Cox proportional regression model was used to identify 17 ARGs associated with the overall survival (OS) of PCa. Then, a multivariate Cox proportional regression model was used to construct a 6 autophagy-related prognostic genes signature. Patients were divided into low-risk group and high-risk group using the median risk score as a cutoff value. High-risk patients had shorter OS than low-risk patients. Furthermore, the signature was validated by ROC curves. Regarding mRNA and miRNA, 12 differentially expressed miRNAs (DEMs) and 1073 differentially expressed genes (DEGs) were detected via the GEO database. We found that miR-205, one of the DEMs, was negatively regulated the expression of ARG (NKX2-3). Based on STRING analysis results, we found that the NKX2-3 was moderately related to the part of genes among the 6 autophagy-related genes prognostic signature. Further, NKX 2-3 was significantly correlated with OS and some clinical parameters of PCa by cBioProtal. By gene set enrichment analysis (GSEA). Lastly, we demonstrated that the association between NKX2-3 and tumor mutation burden (TMB) and PDCD1 (programmed cell death 1) of PCa.Results: We identified that the six ARGs expression patterns are independent predictors of OS in PCa patients. Furthermore, our results suggest that ARGs and miRNAs are inter-related. MiR-205 was negatively regulated the expression of ARG (NKX2-3). Further analysis demonstrated that NKX2-3 may be a potential biomarker for predicting the efficacy of anti-PD-1 therapy in PCa.Conclusions: The current study may offer a novel autophagy-related prognostic signature and may identify a promising miRNA-ARG pathway for predicting the efficacy of anti-PD-1 therapy in PCa.

Comparison of clinical outcomes with IMRT and proton therapy for prostate cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16555-e16555
Author(s):  
Nancy P. Mendenhall ◽  
William Wong ◽  
Curtis Bryant ◽  
Sujay A. Vora ◽  
Randal H. Henderson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Clinical Outcomes ◽  
Ultrasound Image ◽  
Low Risk ◽  
Intermediate Risk ◽  
Image Guided ◽  
Frequent Use ◽  
Gu Toxicity ◽  
Risk Patients

e16555 Background: The ProtecT trial underscores the importance of treatment in men with prostate cancer and life expectancies > 10 years and the validity of radiation therapy (RT). RT can be given with photons or protons (PT). To address the controversy of which is better, clinical outcomes of photon-based intensity modulated RT (IMRT) and PT cohorts from 2 institutions were directly compared. Methods: Under respective IRB approvals, data from 2 cohorts were analyzed. The first was 301 men treated with ultrasound image guided IMRT from 2000-05 to 75.6 Gy in 42 fractions. The second was 1214 men treated with fiducial image guided PT from 2006-10 to 78 CGE in 39 fractions. Median age and followup were 74 y and 7.2 y for IMRT and 66 y and 5.6 y for PT. Hormone therapy (ADT) was used with IMRT and PT, respectively, in 3% and 7% of low-risk patients, 25% and 9.9% of intermediate-risk, and 91% and 57.8% of high-risk. Comparative endpoints were age-stratified 5-year (5Y) survival (OS), ≥ grade 3 gastrointestinal (GI) and urologic (GU) toxicity, and 5Y freedom from biochemical progression (FFBP). Results: There was a lower prevalence of GI (1.3% vs 0.1%, p = 0.0065) and GU (4.3% vs 0.1%, p < 0.0001) toxicity at last follow-up in the PT group. In the IMRT and PT cohorts, OS rates were 90.8% and 88.7% in men ≥75 (p = 0.4083). In men < 75, OS rates were 91.6% and 97.5% in the IMRT and PT low-risk patients (p = 0.003), 92.1% and 95.5% in the IMRT and PT intermediate-risk (p = 0.0535), and 92.0% and 90.0% (p = 0.4975) in the IMRT and PT high-risk. In the IMRT and PT cohorts, respectively, FFBP rates were 92.2% and 98.9% for low-risk patients (p < 0.0001), 87.3% and 94.5% for intermediate-risk patients(p = 0.0226), and 80.3% and 74.4% for high-risk patients (p = 0.5154). Conclusions: In this retrospective comparison of outcomes in cohorts of men treated with IMRT and PT for prostate cancer, FFBP rates were better with PT for men with low- and intermediate-risk disease and similar in men with high-risk disease despite longer and more frequent use of ADT in the IMRT cohort. This study underscores the difficulty of comparing retrospective series, with differences noted in age, RT dose, and ADT use between cohorts. However, the magnitude of improvement with PT is intriguing and warrants prospective testing.

Impact of genomic risk scores on treatment decisions following radical prostatectomy in a prospective Medicare registry.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 72-72
Author(s):  
John L. Gore ◽  
Darlene Dai ◽  
Robert Benjamin Den ◽  
Kasra Yousefi ◽  
Tiffany Le ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
High Risk ◽  
Radical Prostatectomy ◽  
Treatment Decisions ◽  
Low Risk ◽  
Oncologic Outcomes ◽  
Risk Scores ◽  
Risk Patients ◽  
The Impact

72 Background: Prostate cancer patients and providers confront uncertainty as they consider adjuvant or salvage radiation therapy (ART, SRT) after radical prostatectomy (RP). We prospectively evaluated the impact of the Decipher RP test, which predicts metastasis risk after RP, on decision-making for postoperative radiation therapy. Methods: Between October 2016 and May 2017, 1,319 patients treated with RP and considering ART or SRT were enrolled into a Medicare Certification and Training Registry (CTR). Providers submitted a management recommendation based on initial clinical and pathology findings prior to obtaining the Decipher RP test and again upon receiving test results. Only Medicare patients that met the Local Coverage Determination inclusion criteria (i.e., non-organ confined prostate cancer or positive margins or rising PSA) and whose provider was certified in the CTR registry were included in the analysis. Results: Based on clinical variables alone, treatment was recommended for 26% of adjuvant and 19% of salvage patients. Obtaining a Decipher score, changed treatment recommendations in 34% (95% CI 30-39%) and 28% (95% CI 19-38%) of men considering adjuvant or salvage therapy respectively. Among men considering ART, 9% of Decipher low risk patients and 45% of Decipher high-risk patients were recommended treatment. Multivariable logistic regression demonstrated that – independent of pathology risk factors, a high-risk Decipher score was associated with an odds ratio of 7.3 (95% CI 3.9-14.2 p < 0.001) in the adjuvant and 5.5 (95% CI, 1.3-27.8, p = 0.026) in the salvage setting. Conclusions: A prospective CTR demonstrated that use of Decipher resulted in significant changes in treatment decisions for Medicare beneficiaries with PCa considering adjuvant and salvage therapies. Ongoing prospective studies aim at determining how increased use of therapy in men with high Decipher risk impacts oncologic outcomes and whether decreased use in Decipher low risk individuals improves health related quality of life without harming patient survival.

Care received by rural and urban patients with newly diagnosed prostate cancer: Results from a population-based prospective cohort.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 203-203
Author(s):  
Xinglei Shen ◽  
Ying Cao ◽  
Aaron J Katz ◽  
Deborah Usinger ◽  
Sarah Walden ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Bone Scan ◽  
Population Based ◽  
Low Risk ◽  
Rural Residence ◽  
Newly Diagnosed ◽  
Rural And Urban ◽  
Risk Patients ◽  
Rural Patients

203 Background: Rural residence is a source of disparity in cancer access and outcomes. It is not known to what extent rurality affects access to care in patients with prostate cancer. Methods: The North Carolina Prostate Cancer Comparative Effectiveness & Survivorship Study (NC ProCESS) is a population-based cohort of newly-diagnosed prostate cancer patients. Patients were enrolled from 2011-2013 through collaboration with the state cancer registry at diagnosis and followed prospectively. Urban/rural residence was defined by the rural urban continuum code (RUCC): 1-3 (urban) and 4-9 (rural). Medical records were collected and abstracted for prostate cancer care received. Individual-level sociodemographic information was collected by patient report. Results: Among 1,456 NC ProCESS participants with a median age of 65 years, 1089 were categorized as urban and 367 (25%) rural. This is a sociodemographically diverse cohort with 30.2% non-White (including 26.9% Black), 34.1% with high school education or less, and 37.3% with household income < = $40,000. The distance to travel for diagnostic scans was greater for rural patients (miles): CT (7.5 urban vs 17.1 rural, p = 0.07), MRI (8.1 vs 12.0, p = 0.04) and bone scan (6.8 vs 14.1, p = 0.009). However, there was no difference in the percent of patients who underwent CT (15.9% urban vs 12.8% rural, p = 0.15), MRI (7.8% vs 8.2%, p = 0.81) and bone scan (15.9% vs 19.4%, p = 0.13); or the percentage of patients with high risk or metastatic disease who had any staging scan (64.2% vs 66.6% p = 0.8). While all patients consulted with a urologist, rural patients were less likely to have had consultation with a radiation oncologist (42.4% vs 35.8%, p = 0.04). Rural patients were also more likely to report that treatment was more difficult due to travel, including robotic prostatectomy (6.8% vs 13.9% p = 0.001) and radiation therapy (8.01% vs 16.07%, p = 0.001). In patients with low risk cancer, rural patients were more likely to have reported treatment at 12 months (68.2% vs 58.7% p = 0.04) instead of surveillance or observation. For high risk patients, both rural and urban patients reported high rates of treatment by 3 months (96.3% vs 91.3%, p = 0.40). After adjustment for age, income, race, education and insurance, rural residence was associated with increased likelihood of receiving treatment at 1 year (OR 1.54, CI 0.99 – 2.39) in low risk patients, but not associated with receiving treatment at 3 months (OR 3.63, CI 0.24 -54.5) among high risk patients. Conclusions: In a population-based cohort, rural patients with prostate cancer have greater barriers such as travel distance, but similar proportions of rural and urban patients received staging scans and timely treatment for high-risk prostate cancer. Rural patients were less likely to receive multidisciplinary consultation prior to treatment, and were less likely to have surveillance for low risk disease.

Risk-Adapted Androgen Deprivation and Escalated Three-Dimensional Conformal Radiotherapy for Prostate Cancer: Does Radiation Dose Influence Outcome of Patients Treated With Adjuvant Androgen Deprivation? A GICOR Study

2005 ◽  
Vol 23 (27) ◽  
pp. 6561-6568 ◽  
Author(s):  
Almudena Zapatero ◽  
Francisco Valcárcel ◽  
Felipe A. Calvo ◽  
Rosa Algás ◽  
Amelia Béjar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Radiation Dose ◽  
Three Dimensional ◽  
Conformal Radiotherapy ◽  
Androgen Deprivation ◽  
Low Risk ◽  
High Dose ◽  
High Risk Patients ◽  
Risk Patients

Purpose Multicenter study conducted to determine the impact on biochemical control and survival of risk-adapted androgen deprivation (AD) combined with high-dose three-dimensional conformal radiotherapy (3DCRT) for prostate cancer. Results of biochemical control are reported. Patients and Methods Between October 1999 and October 2001, 416 eligible patients with prostate cancer were assigned to one of three treatment groups according to their risk factors: 181 low-risk patients were treated with 3DCRT alone; 75 intermediate-risk patients were allocated to receive neoadjuvant AD (NAD) 4-6 months before and during 3DCRT; and 160 high-risk patients received NAD and adjuvant AD (AAD) 2 years after 3DCRT. Stratification was performed for treatment/risk group and total radiation dose. Results After a median follow-up of 36 months (range, 18 to 63 months), the actuarial biochemical disease-free survival (bDFS) at 5 years for all patients was 74%. The corresponding figures for low-risk, intermediate-risk, and high-risk disease were 80%, 73%, and 79%, respectively (P = .847). Univariate analysis showed that higher radiation dose was the only significant factor associated with bDFS for all patients (P = .0004). When stratified for treatment group, this benefit was evident for low-risk patients (P = .009) and, more interestingly, for high-risk patients treated with AAD. The 5-year bDFS for high-risk patients treated with AAD was 63% for radiation doses less than 72 Gy and 84% for those ≥ 72 Gy (P = .003). Conclusion The results of combined AAD plus high-dose 3DCRT are encouraging. To our knowledge, this is the first study showing an additional benefit of high-dose 3DCRT when combined with long-term AD for unfavorable disease.

scholarly journals LO98: Optimal length of observation for emergency department patients with syncope: a time to event analysis

CJEM ◽  
2017 ◽  
Vol 19 (S1) ◽  
pp. S62
Author(s):  
V. Thiruganasambandamoorthy ◽  
M. Sivilotti ◽  
M.A. Mukarram ◽  
C. Leafloor ◽  
K. Arcot ◽  
...  
Keyword(s):  
High Risk ◽  
Secondary Analysis ◽  
Structural Heart Disease ◽  
Low Risk ◽  
Event Analysis ◽  
Ecg Monitoring ◽  
Arrhythmia Detection ◽  
Observation Units ◽  
Kaplan Meier ◽  
Risk Patients

Introduction: Concern for occult serious conditions leads to variations in ED syncope management [hospitalization, duration of ED/inpatient monitoring including Syncope Observation Units (SOU) for prolonged monitoring]. We sought to develop evidence-based recommendations for duration of ED/post-ED ECG monitoring using the Canadian Syncope Risk Score (CSRS) by assessing the time to serious adverse event (SAE) occurrence. Methods: We enrolled adults with syncope at 6 EDs and collected demographics, time of syncope and ED arrival, CSRS predictors and time of SAE. We stratified patients as per the CSRS (low, medium and high risk as ≤0, 1-3 and ≥4 respectively). 30-day adjudicated SAEs included death, myocardial infarction, arrhythmia, structural heart disease, pulmonary embolism or serious hemorrhage. We categorized arrhythmias, interventions for arrhythmias and death from unknown cause as arrhythmic SAE and the rest as non-arrhythmic SAE. We performed Kaplan-Meier analysis using time of ED registration for primary and time of syncope for secondary analyses. Results: 5,372 patients (mean age 54.3 years, 54% females, and 13.7% hospitalized) were enrolled with 538 (10%) patients suffering SAE (0.3% died due to an unknown cause and 0.5% suffered ventricular arrhythmia). 64.8% of SAEs occurred within 6 hours of ED arrival. The probability for any SAE or arrhythmia was highest within 2-hours of ED arrival for low-risk patients (0.65% and 0.31%; dropped to 0.54% and 0.06% after 2-hours) and within 6-hours for the medium and high-risk patients (any SAE 6.9% and 17.4%; arrhythmia 6.5% and 18.9% respectively) which also dropped after 6-hours (any SAE 0.99% and 2.92%; arrhythmia 0.78% and 3.07% respectively). For any CSRS threshold, the risk of arrhythmia was highest within the first 15-days (for CSRS ≥2 patients 15.6% vs. 0.006%). ED monitoring for 2-hours (low-risk) and 6-hours (medium and high-risk) and using a CSRS ≥2 cut-off for outpatient 15-day ECG monitoring will lead to 52% increase in arrhythmia detection. The majority (82.2%) arrived to the ED within 2-hours (median time 1.1 hours) and secondary analysis yielded similar results. Conclusion: Our study found 2 and 6 hours of ED monitoring for low-risk and medium/high-risk CSRS patients respectively, with 15-day outpatient ECG monitoring for CSRS ≥2 patients will improve arrhythmia detection without the need for hospitalization or observation units.

scholarly journals Identification of Previously Unrecognized Multiple Myeloma Risk Subgroups with a Novel Biological Disease Stratifier

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4718-4718
Author(s):  
Afsaneh M. Shariatpanahi ◽  
Sarah Grasedieck ◽  
Matthew C. Jarvis ◽  
Faezeh Borzooee ◽  
Reuben S. Harris ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Risk Score ◽  
Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
Disease Biology ◽  
Kaplan Meier ◽  
Risk Patients ◽  
Patient Subgroups

Abstract Background: The prognosis of MM is determined by affected organs, tumor burden as measured by e.g., the international staging system (ISS), disease biology such as cytogenetic abnormalities, and response to therapy. The outcome of high-risk MM patients classified by ISS or adverse risk cytogenetics is not uniform and patients show heterogeneous survival. Recent insights into the pathogenesis of MM highlighted genome/transcriptome editing as well as inflammation as drivers for the onset and progression of MM. We hypothesized that inclusion of molecular features into risk stratification could potentially resolve the challenge of accurately distinguishing between high-risk and low-risk MM patients at initial diagnosis and improve outcome. Aim: We aimed to create a simple molecular risk score to identify unrecognized patient subgroups, who have been previously misclassified by current risk stratifiers. Method: The Multiple Myeloma Research Foundation CoMMpass study genomics dataset, combining mRNA Seq and clinical data from more than 700 MM patients, allowed us to evaluate the prognostic value of demographic and clinical parameters, cytogenetics, and gene expression levels of APOBEC genes as well as inflammation-modulating cytokines in MM patients. We calculated hazard ratios and Kaplan-Meier survival estimates for all extracted features. Combining clinical variables that were significantly associated with PFS and OS, we then applied machine learning approaches to identify the most accurate classification model to define a new risk score that is easy to compute and able to stratify NDMM patients more accurately than cytogenetics-based classifiers. Based on a Kaplan-Meier survival curve analysis, we then evaluated the performance of our newly built EI score in sub-classifying of current multiple myeloma risk stratifiers. Results: Based on machine learning models, we defined a weighted OS/PFS risk score (Editor-Inflammation (EI) score) based on mRNA expression of APOBEC2, APOBEC3B, IL11, TGFB1, TGFB3, as well as ß2-microglobulin and LDH serum levels. We showed that the EI score subclassified patients into high-risk, intermediate-risk, and low-risk prognostic groups and demonstrated superior performance (C-index: 0.76) compared to ISS (C-index: 0.66) and R-ISS (C-index: 0.64). We further showed that EI low-risk patients do not benefit from autograft and maintenance therapy. Re-classification of ISS (Figure 1a, b, c) and R-ISS risk groups further confirmed the superiority of the EI score. In addition, the EI score identified previously unrecognized distinct subgroups of MM patients with adverse risk cytogenetics but good prognosis (Figure 1d, e, f). For example, the EI score excellently subclassified del(17p) MM patients into three main risk subgroups including a super low-risk group (none of them has p53 mut) with 5-year OS of 100%, an intermediate-risk group (30% of these patients also have p53 mut) with 5-year OS rate of 75%, and a very poor prognosis group of patients (40% of these patients also have p53 mut) with 5-year OS rate of 0% (2y OS: 40%) (Figure 1f). In line, we could show that patients with del(17p) and high EI score exhibit an enrichment of APOBEC induced genomic mutations compared to intermediate-risk and low-risk patients supporting the hypothesis that del(17p) along with high APOBEC expression levels activate the APOBEC mutation program and thus create an optimal environment for tumor progression. These findings support the necessity of a prognostic score that more accurately reflects MM disease biology. Conclusion: Although MM is considered as an incurable disease, an improved risk stratification could help to identify previously unrecognized low- and high-risk patient subgroups that are over- or undertreated and lead to improved outcomes. Our EI score is a simple score that is based on recent insights into MM biology and accurately identifies high-risk and low-risk newly diagnosed MM patients as well as misclassified MM patients in different cytogenetic and ISS risk subgroups. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Low Absolute Lymphocyte Count (ALC) at Diagnosis Is An IPSS-Independent Predictor of Poorer Survival in Myelodysplastic Syndromes (MDS)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3633-3633
Author(s):  
Nisha L Jacobs ◽  
Shernan G Holtan ◽  
Luis F Porrata ◽  
Svetomir N Markovic ◽  
Ayalew Tefferi ◽  
...  
Keyword(s):  
High Risk ◽  
Median Survival ◽  
Lymphocyte Count ◽  
Scoring System ◽  
Risk Group ◽  
Prognostic Significance ◽  
Multivariate Model ◽  
Low Risk ◽  
Kaplan Meier ◽  
Risk Patients

Abstract Background: The prognostic significance of lymphocyte counts and immune status has been carefully examined in lymphoid malignancies, but the importance of the lymphocyte count in chronic myeloid neoplasms is less clear. In a recent analysis of MDS cases associated with deletion of chromosome 5q (Holtan SG et al AmJHem 2008 Epub 12Jun), we observed that an ALC >1.2 × 109 cells/L at diagnosis is independently associated with improved survival. The prognostic value of ALC in MDS not associated with del(5q) is unknown. Methods: We reviewed the medical records of patients without del(5q) diagnosed with MDS at our institution over a 10-year period and gathered data on complete blood counts and leukocyte differentials, bone marrow findings, and clinical course. Inclusion criteria included diagnosis within 6 months prior to initial consultation at our institution and <20% marrow blasts. Patients were classified according to the International Prognostic Scoring System (IPSS) and the WHO-classification based Prognostic Scoring System (WPSS). Results: The median age of the 503 included patients (360 M, 143 F) was 69 years (range 20–91). Median follow-up was 14 months, and 65% of patients were known to have died with an overall median survival of 36 months. Cytogenetic results as classified by the IPSS were favorable in 326 (65%) patients, intermediate in 112 (22%), and poor in 65 (13%). Both IPSS and WPSS accurately stratified patients, but the WPSS was better at identifying the lowest and highest risk patients. Survival by IPSS risk group was as follows: low-risk disease (n=95, median survival 41.8 months), intermediate-1 (n=285, 23.6 months), 106 with intermediate-2 (n=106, 14.1 months), and high-risk (n=17, 8.05 months). WPSS risk groups included very low risk (n=87; median survival 71.9 months), low risk (n=149, 28.8 months), intermediate risk (n=85, 19.3 months), high risk (n=143, 14.4 months), and very high risk (n=39, 8.8 months). In univariate analysis, factors associated with poorer survival included advanced age (p = 0.0012), higher-risk WHO subtype (p<0.0001), increased marrow blast percentage (p<0.0001), poor-risk karyotype (p<0.0001), higher IPSS score or WPSS score (p<0.0001), lower hemoglobin (p<0.0001), lower MCV (p=0.03), lower ALC (p=0.001), and lower platelets (p=0.001). Factors not associated with survival included sex and ANC. In a multivariate model including only baseline CBC parameters, hemoglobin >10 g/dL (p < 0.001), MCV >96 fl (p = 0.0493), ALC >1.2 × 109/L (p = 0.0449), and platelet count >100 × 109/L (p = 0.0046) were associated with improved survival. A high baseline ALC also maintained independent prognostic significance in a multivariate model against the IPSS (RR 0.746, 95% CI: 0.598, 0.933, p = 0.0099), and the raw WPSS score (RR 0.791, 95% CI 0.633, 0.987, p=0.037) but not the WPSS group (p=0.0794). There was no significant difference in the distribution of IPSS scores between the ALC >1.2 × 109 cells/L and the ALC ≤ 1.2 × 109 cells/L groups, although there were significantly more WPSS high risk patients in the low baseline ALC group (p = 0.0163). The creation of an ALC-modified IPSS score by adding 0.5 point for an ALC ≤ 1.2 × 109 cells/L resulted in a significant increase in median overall survival of the low risk group (41.8 months versus 66.1 months, p < 0.001, Figure 1). Conclusion: ALC is a novel and easily obtained prognostic marker in MDS that provides information complementary to existing prognostic scoring systems. Figure 1. Kaplan-Meier curves based upon IPSS (a) and the ALC-modified IPSS (b), where 0.5 point was added for an ALC ≤ 1.2 × 109 cells/L. Figure 1. Kaplan-Meier curves based upon IPSS (a) and the ALC-modified IPSS (b), where 0.5 point was added for an ALC ≤ 1.2 × 109 cells/L.

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