Association of Comorbidities With Overall Survival in Myelodysplastic Syndrome: Development of a Prognostic Model

Purpose Patients with cancer often experience comorbidities that may affect their prognosis and outcome. The objective of this study was to determine the effect of comorbidities on the survival of patients with myelodysplastic syndrome (MDS). Patients and Methods We conducted a retrospective cohort study of 600 consecutive patients with MDS who presented to MD Anderson Cancer Center from January 2002 to December 2004. The Adult Comorbidity Evaluation-27 (ACE-27) scale was used to assess comorbidities. Data on demographics, International Prognostic Scoring System (IPSS), treatment, and outcome (leukemic transformation and survival) were collected. Kaplan-Meier methods and Cox regression were used to assess survival. A prognostic model incorporating baseline comorbidities with age and IPSS was developed to predict survival. Results Overall median survival was 18.6 months. According to the ACE-27 categories, median survival was 31.8, 16.8, 15.2, and 9.7 months for those with none, mild, moderate, and severe comorbidities, respectively (P < .001). Adjusted hazard ratios were 1.3, 1.6, and 2.3 for mild, moderate, and severe comorbidities, respectively, compared with no comorbidities (P < .001). A final pognostic model including age, IPSS, and comorbidity score predicted median survival of 43.0, 23.0, and 9.0 months for lower-, intermediate-, and high-risk groups, respectively (P < .001). Conclusion Comorbidities have a significant impact on the survival of patients with MDS. Patients with severe comorbidity had a 50% decrease in survival, independent of age and IPSS risk group. A comprehensive assessment of the severity of comorbidities helps predict survival in patients with MDS.

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Obesity Is Poor Prognostic Factor in Lower Risk Myelodysplastic Syndrome

Blood ◽

10.1182/blood.v118.21.5018.5018 ◽

2011 ◽

Vol 118 (21) ◽

pp. 5018-5018

Author(s):

Asmita Mishra ◽

Dana E Rollison ◽

Najla H Al Ali ◽

Maria Corrales-Yepez ◽

Pearlie K Epling-Burnette ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factor ◽

Myelodysplastic Syndrome ◽

Lower Risk ◽

Cox Regression ◽

Cancer Center ◽

Kaplan Meier ◽

Baseline Characteristics ◽

Md Anderson ◽

The Impact

Abstract Abstract 5018 Background: Obesity was associated with a more than 2-fold greater risk of myelodysplastic syndrome (MDS) in a recent epidemiological study (Ma et al, Am J Epidemiol. 2009 June 15; 169(12): 1492–1499). The impact of obesity on outcome of disease in patients with an established diagnosis of MDS has not been studied. We examined the prognostic value of obesity in a large cohort of lower risk MDS patients treated at the Moffitt Cancer Center (MCC). Methods: Data were collected retrospectively from the Moffitt Cancer Center (MCC) MDS database and individual charts reviewed. The primary objective was to evaluate the impact of obesity on overall survival (OS) in lower risk patients with MDS. Patients with low or intermediate-1 (int-1) risk disease by International Prognostic Scoring System (IPSS) were included. Obesity was defined as a body mass index (BMI) ≥ 30 (Standard definition) measured at time of referral to MDS program at MCC. Patients were divided into two groups according to BMI ≥ 30 or BMI < 30. All analyses were conducted using SPSS version 19.0. Chi square and independent t-test were used to compare baseline characteristics between the 2 groups for categorical and continuous variables, respectively. The Kaplan–Meier method was used to estimate median overall survival. Log rank test was used to compare Kaplan–Meier survival estimates between two groups. Cox regression was used for multivariable analysis. Results: Between January 2001 and December 2009, 479 low/int-1 IPSS risk MDS patients were included. Among those, 132 (27.6%) had BMI ≥ 30 and 325 (67.8%) had BMI <30; BMI was missing in 22 patients (4.6%). The baseline characteristics between the two groups were comparable. No difference was noted in mean age, WHO subtype, karyotype, MD Anderson risk model group, red blood cell transfusion dependency (RBC-TD), or serum ferritin (Table-1). The median OS was 59 mo (95%CI 48–70) in patients with BMI <30 compared to 44 (95%CI 38–50) in patients with BMI ≥ 30. (p=0.03). There was no difference in rate of AML transformation according to BMI, 12.9% and 15.7% respectively for BMI ≥ 30 and BMI <30. (P=0.3). In Cox regression analysis obesity predicted inferior OS (Hazard ratio (HR) 1.7 (95%CI 1.15–2.4) (P=0.007) after adjustment for age, MD Anderson risk group, serum ferritin, RBC-TD, use of hypomethylating agents and tobacco use. Conclusion: Our data suggest that obesity is an independent adverse prognostic factor for OS in patients with lower risk MDS. Obesity may be associated with other comorbidities and metabolic dearrangements that contribute to the pathogenesis of the underlying disease. Disclosures: No relevant conflicts of interest to declare.

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Validation of the Newly Proposed MD Anderson Prognostic Risk Model for Patients with Myelodysplastic Syndromes

Blood ◽

10.1182/blood.v116.21.444.444 ◽

2010 ◽

Vol 116 (21) ◽

pp. 444-444

Author(s):

Maria Corrales-Yepez ◽

Jeffrey E. Lancet ◽

Alan F. List ◽

Mohamed A. Kharfan-Dabaja ◽

Teresa Field ◽

...

Keyword(s):

Overall Survival ◽

High Risk ◽

Myelodysplastic Syndromes ◽

Risk Model ◽

Cox Regression ◽

Risk Group ◽

Risk Groups ◽

Refractory Anemia ◽

Kaplan Meier ◽

Md Anderson

Abstract Abstract 444 Background: The international prognostic scoring system (IPSS) is the most widely used clinical tool for risk stratification and tailoring treatment in myelodysplastic syndromes (MDS). Despite its utility, the IPSS has several limitations. The IPSS was developed using outcomes of untreated primary MDS patients at time of diagnosis, and does not account for patient age, performance, and degree of cytopenia. The recently reported MD Anderson risk model (MDAS) addresses many of the limitations of IPSS (Kantarjian et al, CANCER September 15, 2008 / Volume 113 / Number 6). We validated this new risk model in a large external single institution cohort of patients. Methods: Data were collected retrospectively from Moffitt Cancer Center (MCC) MDS database and chart review of patients with MDS. The primary objective was to validate the new risk model calculated at time of initial presentation MCC. The MDAS was calculated as published based on age, performance status, blast%, degree of thrombocytopenia, cytogenetics, white blood cell count, and prior history if transfusion. Patients were divided into four risk groups: low (0-4 points), int-1 (5-6 points), int-2 (7-8 points), and high risk (≥ 9 points). All analyses were conducted using SPSS version 15.0. (SPSS Inc, Chicago, IL). The Kaplan–Meier method was used to estimate median overall survival. Log rank test was used to compare Kaplan–Meier survival estimates between two groups. Cox regression was used for multivariable analysis. Results: Between January 2001 and December 2009, 844 patients were captured by MCC MDS database. The median age was 69 years, MDS subtypes were coded as Refractory anemia (RA) 98 (12%), refractory anemia with ring sideroblasts (RARS) 76 (9%), MDS with del(5q) 20 (2.4%), refractory cytopenia with multi-lineage dysplasia (RCMD) 96 (11%), refractory anemia with excess blasts (RAEB) 255 (30%), therapy related MDS 22 (2.6%), and MDS-nos 275 (33%). IPSS risk groups were low risk in 158 (18.7%), intermediate-1 (int-1) 362 (42.9%), intermediate-2 (int-2) 168 (19.9%), high risk 45 (5.3%), and missing in 111 (13.2%). Based on the new risk model 169 patients (20%) were low risk, 250 (29.6%) int-1, 182 (21.6%) int-2, 135 (16%) high risk, and 94 (11.1%) were unknown. The median OS for all patients was 36 months (95% CI 31.5–40.5 mo). Age, IPSS risk group, serum ferritin, and RBC transfusion dependence were all significant prognostic factors in univariable analysis. The median OS was 92 mo (95%CI 68.1–115.9 mo), 49 mo (95%CI 40.4–57.6 mo), 26 mo (95%CI 21.2–30.8 mo), and 15 month (95%CI 11.8–42.1 mo) respectively for patients with low, int-1, int-2 and high risk patients according to MDAS. (Figure-1) (P < 0.005). In patients with low/int-1 IPSS risk group the median OS according to MDAS was 92 mo (95%CI 68.3–115.7 mo), 49 mo (95%CI 49.3–58.7 mo), 28 mo (95%CI 20.7–35.3), and 19 mo(95% CI 9.9–28.1 mo) respectively for patients with low, int-1, int-2, high risk MDAS (p<0.005). In patients with int-2/high IPSS risk categories only 4 patients were reclassified as low MDAS risk and the median OS for those patients was 10 month (95% CI 0–38 mo). The median OS was 49 mo (95%CI 23.5–74.5 mo), 23 mo (95%CI 19.4–26.6 mo), 14 mo (95% CI 11.5–16.5 mo). (p<0.005). For all the patients the rate of AML transformation according to MDAS was 5.9%, 16.8%, 36.3%, and 50.4% respectively for low, int-1, int-2, and high risk MDAS groups. (p <0.005). In Cox regression analysis, higher risk MDAS predicted inferior OS (Hazard ratio (HR) 1.54 (95%CI 1.35–1.75) (p <0.005) independent of IPSS risk group (HR 1.25 95%CI 1.1–1.45) (p =0.004). Conclusion: Our data validates the prognostic value of the MDAS risk model which was predictive for overall survival and AML transformation. The MDAS complements the IPSS particularly in low/int-1 risk group by identifying patients with higher risk disease behavior and inferior outcome. The utility of this model as a treatment decision tool should be studied prospectively. Disclosures: No relevant conflicts of interest to declare.

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Effect Of Comorbidities In Myelodysplastic Syndrome By Revised-IPSS and Age

Blood ◽

10.1182/blood.v122.21.1530.1530 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1530-1530

Author(s):

Naval G. Daver ◽

Kiran Naqvi ◽

Tapan M. Kadia ◽

Courtney D. DiNardo ◽

Farhad Ravandi ◽

...

Keyword(s):

Stem Cell ◽

Myelodysplastic Syndrome ◽

Median Survival ◽

Research Funding ◽

Comorbidity Score ◽

Kaplan Meier ◽

Comorbidity Scores ◽

Severe Comorbidity ◽

Very High

Abstract Background Comorbidites play a crucial role in the prognosis, treatment and outcomes of patients with hematological malignancies. We have previously reported the impact of comorbidities independent of age and IPSS score (1). The aim of this study was to determine whether comorbidities continued to have a similar impact when patients were reclassified according to the Revised-International Prognostic Scoring System (RIPSS). Methods We reviewed the medical records of 600 consecutive MDS patients who presented to MD Anderson Cancer Center from January 2002 to June 2004. The Adult Comorbidity Evaluation-27 (ACE-27), a validated 27-item comorbidity index for cancer patients (2), was used to assess the severity of comorbid conditions. For each patient, we obtained demographic data and specific staging information based on the R-IPSS. We also collected information on stem cell transplantation (SCT), mortality and survival. Kaplan-Meier methods and log-rank tests were used to assess survival. Results Of the 600 patients included in this study, 402 (67%) were male, and 517 (86%) were white; median age at presentation was 66 years (17 – 94); mean duration of follow-up was 54 months (1 - 100). A total of 34, 117, 131, 129, 165 patients were R-IPSS very low, low, intermediate, high and very high respectively. The ACE-27 comorbidity scores were as follows: none, 137 patients (23%); mild, 254 (42%); moderate, 127 (21%); and severe, 82 (14%). 476 (79%) patients died, and 54 (9%) patients underwent SCT. Overall median survival using the Kaplan-Meier method was 16 months (1 – 100). Median survival according to ACE-27 scores was: 28 months for no comorbidity, 16 months for mild comorbidity, 14 months for moderate comorbidity, and 9 months for severe comorbidity with a P-value of P<0.001. The median survival by R-IPSS was 47 , 34, 21, 16, 6 months for patients in very low, low, intermediate, high and very high risk groups respectively (P<0.001). Of the 54 patients who had SCT, 27 (50 %) died. The median survival of patients who did not undergo stem cell transplantation was 23, 16, 4, 8 months for patients with no, mild, moderate and severe comorbidity scores, respectively (P<0.001). The ACE-27 comorbidity score significantly impacted the median OS of patients in the intermediate (P<0.001) , high (P=0.045) , and very high (P=0.004) R-IPSS groups; but did not significantly impact the median OS in the low (P=0.11) and very low (P=0.49) groups. See figures 1 – 5 below. The ACE-27 comorbidity score significantly impacted the median OS of patients </=65 years (P<0.001) but did not significantly impact those >65 years (P=0.18). Conclusion Comorbidities had a significant impact on the survival of patients with myelodysplastic syndrome, especially among those with more advanced disease and younger age (</= 65). Among the intermediate, high and very high R-IPSS groups the patients with higher ACE-27 comorbidity scores had a significantly shorter survival than those with no comorbidities. The comorbidity scores did not significantly impact survival in the R-IPSS very low and low groups, which may reflect the improved survival and limited number of events that occur in these favorable subsets. Perhaps with longer follow-up a difference in survival may emerge among the favorable R-IPSS subsets. A comprehensive assessment of comorbidity is therefore needed to determine the prognosis in patients with MDS. References 1. Naqvi K, Garcia-Manero G, Sardesai S. Association of comorbidities with overall survival in myelodysplastic syndrome: Development of a prognostic mode. J Clin Oncol. 2011;29(16):2240-6. 2. Piccirillo JF, Tierney RM, Costas I, et al. Prognostic importance of comorbidity in a hospital-based cancer registry. JAMA. 2004;291:2441-47. Disclosures: Ravandi: Sunesis: Consultancy, Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Teva: Consultancy, Honoraria; Pfizer: Honoraria; Merck: Research Funding; Bayer/Onyx: Consultancy, Honoraria; EMD Serono: Research Funding; Medimmune: Research Funding; Amgen: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria. Garcia-Manero:Novartis Pharmaceutical: Research Funding. Kantarjian:Sanofi-Aventis: Research Funding.

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Validation of New Prognostic Model Including Comorbidities in Patients with Myleodysplastic Syndrome Receiving Hypomethylating Therapy

Blood ◽

10.1182/blood.v118.21.1708.1708 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1708-1708

Author(s):

Young-Don Joo ◽

Je-Hwan Lee ◽

Sung-Doo Kim ◽

Yunsuk Choi ◽

Young-Hun Park ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Model ◽

Conflicts Of Interest ◽

Risk Group ◽

Risk Groups ◽

Cancer Center ◽

Risk Category ◽

Hypomethylating Agents ◽

Group Response ◽

Md Anderson

Abstract Abstract 1708 Introduction: A new prognostic model including comorbidities, which are assessed using the Adult Comorbidity Evaluation-27 (ACE-27), was proposed for the patients with MDS by researchers from MD Anderson Cancer Center, Houston, TX (J Clin Oncol 2011;29: 2240). The model was developed after analysis of 600 patients who presented to the center. We aimed to validate the new prognostic model for the Korean patients with MDS who were treated with hypomethylating agents. Methods: Between September 2006 and October 2010, 149 patients were treated with either azacitidine or decitabine for MDS defined by the WHO classification and chronic myelomonocytic leukemia (CMML) in 3 Korean institutes. The new prognostic model included age (> 65 years, 2 score points), comorbidity assessed by ACE-27 (mild/moderate, 1 point; severe, 3 points), and IPSS (intermediate-2, 2 points; high, 3 points). Patients were divided into one of 3 risk groups: low (score 0–1), intermediate (scores 2–4), and high (scored 5–8). Risk group by the new prognostic model could not be assigned in 10 patients, thus a total of 139 patients were included in this analysis. Azacitidine 75 mg/m2/day was administered as a subcutaneous injection for 7 consecutive days (n=68) and decitabine 20 mg/m2/day as a 1-hour intravenous infusion for 5 consecutive days (n=71). Both agents were repeated every 4 weeks. Clinico-patholoical data including comorbidities were collected at time of hypomethylating therapy. Treatment response was evaluated using modified International Working Group response criteria. Results: Median age was 61 years (range, 23–83); 47 patients were over 65 years old. Overall comorbidity score assessed by ACE-27 was as follows: none (n=65), mild (n=53), moderate (n=15), and severe (n=6). IPSS risk category was low/intermediate-1 in 72, intermediate-2 in 55, and high in 12. Risk group measured by the prognostic model was low in 42 (30.2%), intermediate in 79 (56.8%), and high in 18 (12.9%). Hypomethylating therapy induced hematologic responses (CR/PR/mCR) in 28 patients (20.1%) and rate for overall responses (CR/CR/mCR/HI) was 57.6% (80/139). The treatment responses were not significantly different between 3 risk groups. At a median follow-up time of 27.0 months (range, 3.3–55.5) among surviving patients, 70 patients died and overall survival (OS) probability was 49.5% at 2 years; median OS was 24.1 months (95% CI, 11.7–36.5). OS was significantly different according to the presence of comorbidities (OS at 2 years, none vs. mild/moderate vs. severe, 63.4% vs. 37.5% vs. 33.3%, P=0.006) or risk groups by the prognostic model (OS at 2 years, low vs. intermediate vs. high, 71.1% vs. 46.1% vs. 18.5%, P<0.001). The survival differences by the prognostic model were maintained after adjustment for other variables (low vs. intermediate, HR, 2.810, 95% CI, 1.444–5.468, P=0.002; low vs. high, HR, 6.037, 95% CI, 2.708–13.459, P<0.001). Conclusions: The new prognostic model including comorbidities assessed by ACE-27 was useful to predict overall survival in patients with MDS receiving azacitidine or decitabine, although the model could not predict response to the hypomethylating agents. Disclosures: No relevant conflicts of interest to declare.

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Correlation between blast percentage in myelofibrosis and outcomes: A single-center experience.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e18562 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e18562-e18562 ◽

Cited By ~ 1

Author(s):

Lucia Masarova ◽

Prithviraj Bose ◽

Kate Newberry ◽

Abdallah Abou Zahr ◽

Jorge E. Cortes ◽

...

Keyword(s):

Clinical Characteristics ◽

Cox Regression ◽

Chronic Phase ◽

Cancer Center ◽

Normal Range ◽

Single Center Experience ◽

Kaplan Meier ◽

Significant Difference ◽

Systemic Symptoms ◽

Md Anderson

e18562 Background: Patients with accelerated phase (AP) myelofibrosis (MF; >10% blasts [BL] in bone marrow [BM] or peripheral blood [PB]) have shorter overall survival (OS) than those in the chronic phase (<10% BM/PB BL). However, outcomes of patients with “lower” BM/PB BL (1-9%) are not well described. Methods: Clinical characteristics and OS of 1099 patients with MF who presented to MD Anderson Cancer Center between years 1984 – 2013 were retrospectively evaluated. Kaplan-Meier analysis and Cox regression models were used for calculations and comparisons. Results: PB and BM BL were available for 1038 (94%) patients at presentation. Five percent had AP, 10% had 5-9% BM or PB BL; 45% had < 5% BM BL and 1% (n=282), 2% (n=110), 3% (n=47) or 4% (n=27) PB BL; and 40% had < 5% BM BL and 0% PB BL (normal range). OS was similar among patients with 5-9% BM or 4-9% PB BL and those in AP (P>0.05). OS was also similar among patients with BL in the normal range and those with <5% BM and 1-3% PB BL (p>0.05). By grouping patients with similar OS, we have identified 2 groups with distinctive OS of 54 and 27 months, respectively (Table; p<0.001; HR = 1.81 [95%CI 1.5-2.2]). Five-year leukemia free survival was 65% for those in AP, 76% for ≥ 5-9% BM or ≥ 4-9% PB blasts, and 91% for < 4% BM or ≤ 3% PB BL (P<0.001). Clinical characteristics were similar for patients in the AP and with ≥ 5-9% BM or ≥ 4-9% PB blasts. Both groups had significantly higher leukocytes, lower hemoglobin and platelet levels, and were more likely to be transfusion dependent, have systemic symptoms, and unfavorable karyotype than patients with ≤ 4% BM or ≤ 3% PB blasts. There was no significant difference in age, splenomegaly, BM fibrosis grade, or distribution of JAK2, MPL and CALR mutations among these groups. Conclusions: Patients with ≥ 4% PB or ≥ 5% BM BL have OS that appears to be the same as those with >10% BL, suggesting that these patients may require a more aggressive treatment approach. [Table: see text]

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A Prognostic Autophagy-Related Long Non-coding RNA (ARlncRNA) Signature in Acute Myeloid Leukemia (AML)

Frontiers in Genetics ◽

10.3389/fgene.2021.681867 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chunxia Zhao ◽

Yulu Wang ◽

Famei Tu ◽

Shuai Zhao ◽

Xiaoying Ye ◽

...

Keyword(s):

Cox Regression ◽

Survival Curve ◽

Pearson Correlation ◽

Enrichment Analysis ◽

Risk Groups ◽

Gene Set Enrichment Analysis ◽

Kaplan Meier ◽

Non Coding Rna ◽

Novel Biomarkers ◽

Meier Survival Curve

BackgroundSome studies have proven that autophagy and lncRNA play important roles in AML. Several autophagy related lncRNA signatures have been shown to affect the survival of patients in some other cancers. However, the role of autophagy related lncRNA in AML has not been explored yet. Hence, this study aims to find an autophagy related lncRNA signature that can affect survival for AML patients.MethodA Pearson correlation analysis, a Kaplan–Meier survival curve, a univariate cox regression, and a multivariate cox regression were performed to establish an autophagy related lncRNA signature. A univariate cox regression, a multivariate cox regression, a Kaplan–Meier survival curve, and a ROC curve were applied to confirm if the signature is an independent prognosis for AML patients. The relationship between the signature and the clinical features was explored by using a T test. Gene Set Enrichment Analysis (GSEA) was used to investigate the potential tumor related pathways.ResultsA four-autophagy related lncRNA (MIR133A1HG, AL359715.1, MIRLET7BHG, and AL356752.1) signature was established. The high risk score based on signature was related to the short survival time of AML patients. The signature was an independent factor for the prognosis for AML patients (HR = 1.684, 95% CI = 1.324–2.142, P < 0.001). The signature was correlated with age, leukocyte numbers, and FAB (M3 or non-M3). The P53, IL6/JAK/STAT3, TNF-α, INF-γ, and IL2/STAT5 pathways might contribute to the differences between the risk groups based on signature in AML.ConclusionThe four autophagy related lncRNAs and their signature might be novel biomarkers for predicting the survival of AML patients. Some biological pathways might be the potential mechanisms of the signature for the survival of AML patients.

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Identification of Epithelial–Mesenchymal Transition-Related Prognostic lncRNAs Biomarkers Associated With Melanoma Microenvironment

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.679133 ◽

2021 ◽

Vol 9 ◽

Author(s):

Bo Xiao ◽

Liyan Liu ◽

Zhuoyuan Chen ◽

Aoyu Li ◽

Pingxiao Wang ◽

...

Keyword(s):

Cox Regression ◽

Epithelial Mesenchymal Transition ◽

Enrichment Analysis ◽

Roc Curves ◽

Risk Groups ◽

Gene Set Enrichment Analysis ◽

Gene Set Enrichment ◽

Mesenchymal Transition ◽

Cox Regression Analysis ◽

Kaplan Meier

Melanoma is the most common cancer of the skin, associated with a worse prognosis and distant metastasis. Epithelial–mesenchymal transition (EMT) is a reversible cellular biological process that plays significant roles in diverse tumor functions, and it is modulated by specific genes and transcription factors. The relevance of EMT-related lncRNAs in melanoma has not been determined. Therefore, RNA expression data and clinical features were collected from the TCGA database (N = 447). Melanoma samples were randomly assigned into the training (315) and testing sets (132). An EMT-related lncRNA signature was constructed via comprehensive analyses of lncRNA expression level and corresponding clinical data. The Kaplan-Meier analysis showed significant differences in overall survival in patients with melanoma in the low and high-risk groups in two sets. Receiver operating characteristic (ROC) curves were used to measure the performance of the model. Cox regression analysis indicated that the risk score was an independent prognostic factor in two sets. Besides, a nomogram was constructed based on the independent variables. Gene Set Enrichment Analysis (GSEA) was applied to evaluate the potential biological functions in the two risk groups. Furthermore, the melanoma microenvironment was evaluated using ESTIMATE and CIBERSORT algorithms in the risk groups. This study indicates that EMT-related lncRNAs can function as potential independent prognostic biomarkers for melanoma survival.

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CMET-34. IMPROVEMENT OF LEPTOMENINGEAL DISEASE FOLLOWING INFECTIOUS MENINGITIS

Neuro-Oncology ◽

10.1093/neuonc/noz175.235 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi59-vi59 ◽

Cited By ~ 1

Author(s):

Nicholas Metrus ◽

Carolos Kamiya ◽

Shiao-Pei Weathers ◽

Christa Seligman ◽

Barbara O’Brien

Keyword(s):

Median Survival ◽

Post Infection ◽

Systemic Disease ◽

Cancer Center ◽

Cns Infection ◽

Leptomeningeal Disease ◽

History Of ◽

Md Anderson ◽

To Receive ◽

Systemic Therapies

Abstract INTRODUCTION The incidence of leptomeningeal disease (LMD) is increasing, due to better imaging, earlier diagnosis and improved systemic disease control. However, many of the systemic therapies do not cross the blood brain barrier (BBB) and, despite treatment with radiation and/or intrathecal (IT) chemotherapy, median survival is approximately 4-6months in solid tumors complicated by LMD. Repeated IT injections increase the risk of CNS infection. Preclinical models have shown that infectious meningitis transiently modifies the BBB. METHODS Our series consisted of 6 LMD patients (5 breast cancer primary, 1 lung cancer primary) treated on IT chemotherapy at MD Anderson Cancer Center between 2013 and 2018, who subsequently developed infectious meningitis. Three patients had history of parenchymal metastases in addition to LMD and four had history of radiation to brain and/or spine. LMD was confirmed by cytology and/or imaging. All were treated with IT topotecan. RESULTS CSF cultures were positive for Proprionobacterium acnes in three patients, Pseudomonas aeruginosa in two, and Raoultella ornithinolytica in one, who died shortly thereafter. Antibiotic regimens were variable. Three patients went on to receive IT chemotherapy post-infection (two never discontinued IT chemotherapy throughout infection). Those that had IT chemotherapy post-infection cleared CSF and imaging findings of LMD or maintained stability of radiographic LMD burden until death. No patients died directly from LMD. One patient, who developed infection after Ommaya placement and was never initiated on IT chemotherapy, still cleared his CSF of malignant cells. Excluding the patient who died shortly after meningitis diagnosis, the average time from meningitis diagnosis to death was 8.8 months and the average median survival from LMD diagnosis to death was 14 months. CONCLUSION Our findings support further evaluating the safety and timing of IT chemotherapy with active infectious meningitis and the potential synergistic benefit of increased immunogenicity and chemotherapy in LMD.

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Comorbidities and Myelodysplatic Syndromes.

Blood ◽

10.1182/blood.v114.22.2789.2789 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2789-2789 ◽

Cited By ~ 3

Author(s):

Kiran Naqvi ◽

Guillermo Garcia-Manero ◽

Sagar Sardesai ◽

Jeong Oh ◽

Sherry Pierce ◽

...

Keyword(s):

Cancer Patients ◽

Median Survival ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Hazards Model ◽

Kaplan Meier ◽

Comorbidity Scores ◽

Severe Comorbidity

Abstract Abstract 2789 Poster Board II-765 Background: Cancer patients often experience comorbidities that may affect their therapeutic options, prognosis, and outcome (1). Limited studies have evaluated the characteristics and impact of comorbidities in myelodysplastic syndromes (MDS). The aim of this study was to determine the effect of comorbidities on the survival of patients with MDS. Methods: We reviewed the medical records of 500 consecutive MDS patients who presented to MD Anderson Cancer Center from January 2002 to June 2004. The Adult Comorbidity Evaluation-27 (ACE-27), a validated 27-item comorbidity index for cancer patients (2), was used to assess the severity of comorbid conditions. For each patient, we obtained demographic data and specific staging information based on the International Prognostic Scoring System (IPSS). We also collected information on stem cell transplantation (SCT), mortality and survival. Kaplan-Meier methods and log-rank tests were used to assess survival. Multivariate analysis was performed using the Cox Proportional Hazards Model. Results: Of the 500 patients included in this study, 327 (65.4%) were male, and 436 (87.9%) were white; median age at presentation was 66.6 years (17.7, 93.5); mean duration of follow-up was 23.5 months (0, 88). A total of 49% of patients had IPSS intermediate-1 or lower risk. The ACE-27 comorbidity scores were as follows: none, 106 patients (21.2%); mild, 213 (42.6%); moderate, 108 (21.6%); and severe, 73 (14.6%). Three hundred and eighty one (76.2%) patients died, and 44 (8.8%) patients underwent SCT. Overall median survival using the Kaplan-Meier method was 17.6 months. Median survival according to ACE-27 scores was: 27.9 months for no comorbidity, 18.9 months for mild comorbidity, 15.2 months for moderate comorbidity, and 9.7 months for severe comorbidity. This trend reached statistical significance (p < 0.0001). The median survival by IPSS ranged from 40.9 months for patients in the low risk group versus 8.1 months for those in the high risk category (p < 0.0001). The hazards ratio obtained from the multivariate Cox Proportional Hazards Model was 1.5 and 2.0 for moderate and severe comorbidity scores when adjusted for age and IPSS (p < 0.0001). A linear trend was also observed between the severity of comorbidity and having received SCT (p = 0.001). Of the 44 patients who had SCT, 21 (47.7%) died. The median survival of patients who did not undergo stem cell transplantation ranged from 22.7 months for patients with no comorbidity to 9.3 months for patients with severe comorbidity (p = 0.0002). Conclusion: Comorbidities had a significant impact on the survival of patients with myelodysplastic syndrome. Patients with higher ACE-27 comorbidity scores had a shorter survival than those with no comorbidity, independent of their age and the IPSS risk group. Also patients with comorbid conditions received SCT less often than those without comorbidity. A comprehensive assessment of comorbidity is therefore needed to determine the prognosis in patients with MDS. References: (1) Extermann M. Measurement and impact of comorbidity in older cancer patients. Crit Rev Oncol Hematol. 2000;35:181-200. (1) Piccirillo JF, Tierney RM, Costas I, et al. Prognostic importance of comorbidity in a hospital-based cancer registry. JAMA. 2004;291:2441-47. Disclosures: No relevant conflicts of interest to declare.

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The Clinical and Biological Studies of Myelodysplastic Syndrome

Blood ◽

10.1182/blood.v126.23.5247.5247 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5247-5247

Author(s):

Aining Sun ◽

Tongtong Zhang ◽

Suning Chen ◽

Wu Depei

Keyword(s):

Survival Analysis ◽

Myelodysplastic Syndrome ◽

Median Survival ◽

Scoring System ◽

Chromosome Abnormalities ◽

Survival Duration ◽

International Prognostic Scoring System ◽

Male And Female ◽

Median Survival Duration ◽

Who 2008

Abstract Objective: To analyse systematically the clinical and biological characteristics of 2080 myelodysplastic syndrome patients in our laboratory from 1984 to 2013 and to reveal the unique features of MDS patient in our area. Methods: 1. Conventional cytogenetics were performed to investigated the cytogenetics changes in 2080 MDS patients. All patients were classified according to the FAB criterion, in which, 1493 cases were reclassified according to the WHO (2008) criterion; and 550 patients' outcomes were evaluated according to the International Prognostic Scoring System, WHO classification-based Prognostic Scoring System (WPSS) and the revised International Prognostic Scoring System (IPSS-R). 2. We analysed the clinical, cytogenetic characteristics and survival of 2080 MDS patients by statistical methods. Results: 1. According to the FAB criterion: 1040 (50.0%) patients with RA, 135 (6.5%) patients with RARS, 691 (33.2%) patients with RAEB, 145 (7.0%) patients with RAEB-t, and 69 (3.3%) patients with CMML. The median age was 51 years old (range, 5-93 years old). The ratio of male and female was 1.54. 40.3%(839/2080) patients had clonal chromosome abnormalities, in which 277 (13.3%) patients with complexed karyotype. The rate of karyotype abnormalities was higher in RAEB than that in other subtypes. Survival analysis show that the subgroup with RA had a longer median survival duration than the subgroup with RAS, RAEB, RAEB-t, their median survival duration was 50 months, 32 months, 13months and 16 months, respectively. 2. According to the WHO (2008) criterion: 220 patients (14.7%) with RA/RN/RT/RCUD, 75 patients (5.0%) with RARS, 385 patient (25.8%) with RCMD, 14 patient (0.9%) with 5q- syndrome, 282 patients (18.9%) with RAEB-1, 306 patients (20.5%) with RAEB-2, 211 patients (14.1%) with MDS-U. The ratio of male and female was 1.51 (898/595) and the median age was 54 years old (range, 6-93 years old). In all patients, the median hemoglobin level was 70g/L (11~167 g/L), the median platelet count was 51.5×109/L (2~1045 ×109/L) and the median WBC count was 2.65×109/L (0.11~52×109/L). The rate of clonal chromosome abnormalities was 42.1% (628/1493), in which 216 (14.5%) patients with complexed karyotype. There was statistically significant difference in the rate of chromosomal abnormalities among different subtypes (P<0.01). RA/RN/RT/RCUD had a longer median survival duration than other subgroups, in order of MDS-U, RCMD, RARS, RAEB-1 and RAEB-2. 3. Among 2080 patients, 839 patients with clonal chromosome abnormalities. chromosome aberration types mainly uneven anomalies, the most common trisomies or monomer. The most common abnormity was +8. Other aberrations in frequent order was -7/del(7q), del(20q), del(5q), and so on. 4. Stastistics for survival, 550 patients' outcomes were evaluated according to the IPSS, WPSS and IPSS-R. The results show the IPSS, WPSS and IPSS-R score were significantly affected OS (P<0.001). When comparing the prognostic value of the IPSS, WPSS, and IPSS-R, using the Cox regression model, a significantly higher predictive power for OS became evident for the IPSS-R, compared with the IPSS and WPSS. Conclusion: 1. In our study, the MDS patients showed the unique clinical and biological features. We found that the characteristics of cytogenetics has significant differences from western MDS patients. The most common abnormity was +8. Other aberrations in frequent order was -7/del(7q), del(20q), del(5q), and so on. 2. IPSS-R is a powerful tool in MDS survival analysis. Disclosures No relevant conflicts of interest to declare.

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