Refined MD Anderson Prognostic Scoring System (MDAPS-R) for Chronic Myelomonocytic Leukemia (CMML)

Abstract Abstract 3797 Background: Since the time of initial proposal of the MD Anderson Prognostic Score (MDAPS) in 2000, there has been substantial development in diagnosis and treatment for patients (pts) with CMML. MDAPS did not incorporate cytogenetic abnormalities, which is one of the most important factors of prognostication in other myeloid malignancies. Therefore, we analyzed a large cohort of patients with CMML and developed new prognostic scoring system that also incorporates cytogenetic abnormalities (named MDAPS-R). Methods: From 2003 and 2012, we identified 358 pts with diagnosis of CMML, using standards strictly defined by World Health Organization (WHO) criteria. Potential prognostic factors were identified by log-rank test. Of those, independent prognostic factors were extracted after Cox proportional hazard regression. Based on the relative strength of hazard ratio (HR), MDAPS-R was developed and was verified by log-rank test. Result: Median age of the analyzed group was 68 years (range:23–89);113 (32%) pts were female. Two hundred twenty one (62%) pts were classified as CMML-1 and 104 (29%) were CMML-2 (unknown in 33 pts). Thirty nine (11%) pts had prior exposure to chemotherapy and/or radiation therapy. Mean (± SE) white blood cell count (WBC) was 24.5 ± 1.5 (x103/μL), hemoglobin (Hb) was 10.8 ± 0.1(g/dL), platelet count (Plt) was 132 ± 7.0 (x103/μL) and bone marrow blast count (BMBL) was 6.9 ± 0.3 (%), respectively. Cytogenetics was diploid in 224 (63%) pts. Trisomy 8 was detected in 14 (4%) pts, del 20q in 12 (3.4%), -Y in 13 (3.6%), del 7q/-7 in 25 (7%), and del 5q/-5 in 10 (2.8%) pts, respectively. Complex cytogenetic abnormality was detected in 16 (4.5%) pts. Two hundred eighty (78%) pts had RAS mutation analysis and 49 (18%) had NRAS mutation while 16 (5.7%) had KRAS mutation. FLT3 alteration was tested in 297 pts (83%):3 (1%) had D835 mutation while 10 (3.4%) had ITD. JAK2 mutation was tested in 161 (45%) pts of which 19 (12%) had V617F mutation. Less commonly occurring mutations included: NPM1 (5/88 tested), c-kit (3/156), CEBPA (6/83), IDH1 (1/59), IDH2 (3/58), and DNMT3a (1/4). During the median follow up duration of 15 months (range; 1–145), 53 (15%) pts transformed to acute leukemia and 182 (51%) pts died. Median transformation free survival (TFS) and overall survival (OS) of the analyzed group was 24.9 months (range; 1–145) and 26.8 months (range; 1–145), respectively. Log-rank test identified significant covariates in association with OS that include: BMBL (<10 vs. ≥10; P = 0.024), WBC (≤10 vs. >10; P = 0.01), Hb (<12 vs. ≥12; P < 0.001), CMML subtype (CMML-1 vs. 2; P = 0.007), prior exposure to chemo and/or radiation (Yes vs. No; P < 0.001), cytogenetics (diploid vs. complex or del7q/-7 vs. others; P < 0.001), serum β2 microglobulin (β2MG) (≤4.0 vs >4.0; P < 0.001), serum LDH (≤700 vs. >700; P < 0.001), peripheral absolute lymphocyte count (ALC) (≤2.5 vs. >2.5; P < 0.001), and peripheral absolute monocyte count (≤4.0 vs. >4.0; P = 0.012). None of the molecular mutations had impact on OS. After being fitted into Cox proportional hazard regression, following covariates remained independently significant: BMBL ≥10 % (vs. <10; HR = 1.6), Hb < 12 g/dL (vs. ≥12; HR = 1.9), LDH > 700 IU/L (vs. ≤700; HR = 1.5), ALC > 2.5 × 103/μL (vs. <2.5; HR = 1.7), β2MG > 4.0 mg/L (vs. ≤ 4.0; HR = 1.6), and complex cytogenetics or del 7q/-7 (vs. diploid; HR = 2.3 and others vs. diploid; HR = 1.5). We developed MDAPS-R based on relative strength of HR in each of these above factors (1 point assigned to each of the following: BM BL '10 %, Hb<12 g/dL, LDH 700 IU/L, ALC .2.5 × 103/μL, and β2MG > 4.0 mg/L; 0 points for diploid cytogenetics, 2 points for −7/del 7q or complex cytogenetics, and 1 point for all other abnormal karyotype). Among 358 pts, 282 (79%) were evaluable for analysis via MDAPS-R. MDAPS-R stratified pts into 4 distinct prognostic groups: score 0–1 = low risk (N = 70, median OS 56 months), 2–3 = intermediate-1 risk (N = 133, median OS 28 months), 4–5 = intermediate-2 risk (N = 68, median OS 18 months), and 6–7 = high risk (N = 11, median OS 7.5 months) (P < 0.001, Figure 1A). MDAPS-R also predicted TFS in the same cohort (median TFS: low = 54, int-1 = 26, int-2 = 15, and high = 7 months, P < 0.001, Figure 1B). Conclusion: We propose a refined version of MDAPS (MDAPS-R) specifically for pts with CMML that incorporates cytogenetic abnormalities. This model may help risk-stratified decision making in CMML pts. Disclosures: No relevant conflicts of interest to declare.

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The Impact of Beta Blockers on Survival in Heart Transplant Recipients: Insights from the Zabrze HTx Registry

Cardiology Research and Practice ◽

10.1155/2020/5190248 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Grzegorz M. Kubiak ◽

Radosław Kwieciński ◽

Agnieszka Ciarka ◽

Andrzej Tukiendorf ◽

Piotr Przybyłowski ◽

...

Keyword(s):

Beta Blockers ◽

Rank Test ◽

Proportional Hazard ◽

Transplant Recipients ◽

Entire Cohort ◽

Reactive Protein ◽

Cox Proportional Hazard ◽

Log Rank Test ◽

Cox Proportional Hazard Regression ◽

The Impact

Introduction. The data assessing the impact of beta blocker (BB) medication on survival in patients after heart transplantation (HTx) are scarce and unequivocal; therefore, we investigated this population. Methods. We retrospectively analyzed the HTx Zabrze Registry of 380 consecutive patients who survived the 30-day postoperative period. Results. The percentage of patients from the entire cohort taking BBs was as follows: atenolol 24 (17%), bisoprolol 67 (49%), carvedilol 11 (8%), metoprolol 28 (20%), and nebivolol 8 (6%). The patients receiving BBs were older (56.94 ± 14.68 years vs. 52.70 ± 15.35 years, p=0.008) and experienced an onset of HTx earlier in years (11.65 ± 7.04 vs. 7.24 ± 5.78 p≤0.001). They also had higher hematocrit (0.40 ± 0.05 vs. 0.39 ± 0.05, p=0.022) and red blood cells (4.63 (106/μl) ± 0.71 vs. 4.45 (106/μl) ± 0.68, p=0.015). Survival according to BB medication did not differ among the groups (p=0.655) (log-rank test). Univariate Cox proportional hazard regression analysis revealed that the following parameters were associated with unfavorable diagnosis: serum concentration of albumin (g/l) HR: 0.87, 95% CI (0.81–0.94), p=0.0004; fibrinogen (mg/dl) HR: 1.006, 95% CI (1.002–1.008), p=0.0017; and C-reactive protein (mg/l) HR: 1.014, 95% CI (1.004–1.023), p=0.0044. Conclusions. The use of BBs in our cohort of patients after HTx was not associated with survival benefits.

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Multiinstitutional validation of the University of California at San Francisco Low-Grade Glioma Prognostic Scoring System

Journal of Neurosurgery ◽

10.3171/2009.2.jns081101 ◽

2009 ◽

Vol 111 (2) ◽

pp. 203-210 ◽

Cited By ~ 63

Author(s):

Edward F. Chang ◽

Aaron Clark ◽

Randy L. Jensen ◽

Mark Bernstein ◽

Abhijit Guha ◽

...

Keyword(s):

San Francisco ◽

Scoring System ◽

External Validation ◽

University Of California ◽

Rank Test ◽

Low Grade ◽

Proportional Hazard ◽

Cox Proportional Hazard ◽

Log Rank Test ◽

Validation Set

Object Medical and surgical management of low-grade gliomas (LGGs) is complicated by a highly variable clinical course. The authors recently developed a preoperative scoring system to prognosticate outcomes of progression and survival in a cohort of patients treated at a single institution (University of California, San Francisco [UCSF]). The objective of this study was to validate the scoring system in a large patient group drawn from multiple external institutions. Methods Clinical data from 3 outside institutions (University of Utah, Toronto Western Hospital, and University of California, Los Angeles) were collected for 256 patients (external validation set). Patients were assigned a prognostic score based upon the sum of points assigned to the presence of each of the 4 following factors: 1) location of tumor in presumed eloquent cortex, 2) Karnofsky Performance Scale (KPS) Score ≤ 80, 3) age > 50 years, and 4) maximum diameter > 4 cm. A chi-square analysis was used to analyze categorical differences between the institutions; Cox proportional hazard modeling was used to confirm that the individual factors were associated with shorter overall survival (OS) and progression-free survival (PFS); and Kaplan–Meier curves estimated OS and PFS for the score groups. Differences between score groups were analyzed by the log-rank test. Results The median OS duration was 120 months, and there was no significant difference in survival between the institutions. Cox proportional hazard modeling confirmed that the 4 components of the UCSF Low-Grade Glioma Scoring System were associated with lower OS in the external validation set; presumed eloquent location (hazard ratio [HR] 2.04, 95% CI 1.28–2.56), KPS score ≤ 80 (HR 5.88, 95% CI 2.44–13.7), age > 50 years (HR 1.82, 95% CI 1.02–3.23), and maximum tumor diameter > 4 cm (HR 2.63, 95% CI 1.58–4.35). The stratification of patients based on scores generated groups (0–4) with statistically different OS and PFS estimates (p < 0.0001, log-rank test). Lastly, the UCSF patient group (construction set) was combined with the external validation set (total of 537 patients) and analyzed for OS and PFS. For all patients, the 5-year survival probability was 0.79; the 5-year cumulative OS probabilities stratified by score group were: score of 0, 0.98; score of 1, 0.90; score of 2, 0.81; score of 3, 0.53; and score of 4, 0.46. Conclusions The UCSF scoring system accurately predicted OS and PFS in an external large, multiinstitutional population of patients with LGGs. The strengths of this system include ease of use and ability to be applied preoperatively, with the eventual goal of aiding in the design of individualized treatment plans for patients with LGG at diagnosis.

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Pemodelan Regresi Cox Proportional Hazard Pada Data Perceraian

Unisda Journal of Mathematics and Computer Science (UJMC) ◽

10.52166/ujmc.v6i2.2393 ◽

2020 ◽

Vol 6 (2) ◽

pp. 49-58

Author(s):

Haykal Abidin ◽

Novita Eka Chandra ◽

Mohammad Syaiful Pradana

Keyword(s):

Domestic Violence ◽

Predictor Variable ◽

Rank Test ◽

Proportional Hazard ◽

Forced Marriage ◽

Hazard Regression ◽

Model Parameter ◽

Cox Proportional Hazard ◽

Log Rank Test ◽

Cox Proportional Hazard Regression

The purpose of this research is modeling the Cox proportional hazard regression form on divorce data in Pelaihari sub-district, Tanah Laut district, South Kalimantan province. The source of the data comes from the Court Decision in Pelaihari District, Tanah Laut Regency, South Kalimantan. The data analysis technique uses software R with the steps, namely data description, Log-Rank test, checking proportional hazard assumptions, Cox regression model parameter estimation, backward selection with AIC, the best model parameter significance test, calculating Hazard ratio and interpretation of each predictor variable. Based on the results of the analysis and discussion, it was found that for the Log-Rank test, the variable survival time for domestic violence, forced marriage, lying and stories of disgrace differed significantly. While the model that meets the criteria after iteration up to 15 times is the 15th model with the smallest AIC value and p-value <0.05 with factors that significantly influence divorce in Pelaihari sub-district based on modeling results using Cox proportional Hazard regression. are the variables of cheating, gambling, domestic violence, forced marriage, lies, jealousy and disgrace story variables

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Peran Tindakan Revaskularisasi terhadap Kesintasan Pasien Non ST Elevation Myocardial Infarction (NSTEMI)

Jurnal Penyakit Dalam Indonesia ◽

10.7454/jpdi.v1i1.34 ◽

2017 ◽

Vol 1 (1) ◽

pp. 24

Author(s):

Gerie Amarendra ◽

Lukman H Makmun ◽

Dono Antono ◽

Esthika Dewiasty

Keyword(s):

Myocardial Infarction ◽

St Elevation Myocardial Infarction ◽

Rank Test ◽

Proportional Hazard ◽

Hazard Regression ◽

Cox Proportional Hazard ◽

Log Rank Test ◽

Kaplan Meier ◽

St Elevation ◽

Cox Proportional Hazard Regression

Pendahuluan. Pengaruh revaskularisasi terhadap kesintasan pasien non ST elevation myocardial infarction (NSTEMI) masih belum jelas. Waktu revaskularisasi yang optimal pada pasien NSTEMI belum ditemukan. Penelitian ini bertujuan mengetahui pengaruh revaskularisasi terhadap kesintasan pasien NSTEMI, juga mengetahui pengaruh waktu revaskularisasi terhadap kesintasan pasien NSTEMI.Metode. Penelitian dengan disain kohort retrospektif dilakukan terhadap 300 pasien non ST elevation myocardial infarction yang dirawat di RSUPNCM pada kurun waktu Desember 2006-Maret 2011. Data klinis, laboratorium, elektrokardiografi (EKG), ekokardiografi, dan angiografi koroner dikumpulkan. Pasien yang telah terhitung enam bulan setelah onset kemudian dihubungi melalui telepon untuk melihat status mortalitasnya. Perbedaan kesintasan revaskularisasi ditampilkan dalam kurva Kaplan Meier dan perbedaan kesintasan diantara dua kelompok diuji dengan Log-rank test dengan batas kemaknaan <0,05, serta analisis multivariat dengan Cox proportional hazard regression untuk menghitung adjusted hazard ratio (dan interval kepercayaan 95%) antara pasien NSTEMI yang menjalani terapi medikamentosa dan revaskularisasi terhadap kelompok medikamentosa dengan memasukkan variabel perancu.Hasil. Terdapat perbedaan kesintasan yang bermakna pada uji log rank (p<0,001) antara pasien NSTEMI yang menjalani revaskularisasi dan terapi medikamentosa saja dengan crude HR 0,19 (IK95% 0,11-0,34) dan fully adjusted HR 0,33 (IK95% 0,17-0,64). Faktor perancu yang bermakna adalah penurunan fungsi ginjal dan syok kardiogenik. Pada analisis kesintasan berdasarkan waktu revaskularisasi tidak didapatkan perbedaan kesintasan antara pasien yang menjalani revaskularisasi < 1 minggu, 1-2 minggu, 2-3 minggu, 3-4 minggu, 4-5 minggu dengan p=0,853.Simpulan. Kesintasan enam bulan pasien NSTEMI yang menjalani terapi medikamentosa dan revaskularisasi lebih baik dibandingkan dengan terapi medikamentosa saja. Tidak terdapat perbedaan kesintasan enam bulan pasien NSTEMI berdasarkan waktu revaskularisasi.

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Combined adjuvant cisplatin and ifosfamide chemotherapy and radiotherapy for malignant mixed müllerian tumors of the uterus

International Journal of Gynecological Cancer ◽

10.1136/ijgc-00009577-200605000-00063 ◽

2006 ◽

Vol 16 (3) ◽

pp. 1364-1369 ◽

Cited By ~ 1

Author(s):

L. Wong ◽

H. T. See ◽

H. S. Khoo-Tan ◽

J. S. Low ◽

W. T. Ng ◽

...

Keyword(s):

Adjuvant Chemotherapy ◽

Adjuvant Therapy ◽

Rank Test ◽

Proportional Hazard ◽

Cox Proportional Hazard ◽

Log Rank Test ◽

Kaplan Meier ◽

Effect Of Treatment ◽

Cox Proportional Hazard Regression

The role of adjuvant therapy for malignant mixed müllerian tumors of the uterus has not been established. Our aim was to review our experience with sequential adjuvant therapy using cisplatin and ifosfamide chemotherapy and radiotherapy after surgical staging. A retrospective study of 43 patients from 1995 to 2004 was undertaken. Survival was calculated using the Kaplan–Meier method and compared by the log-rank test. The Cox proportional hazard regression model was used to assess the effect of treatment on survival after adjustment for age and stage. Twenty-eight patients received adjuvant chemotherapy and 28 patients had adjuvant radiotherapy. Twenty-one patients underwent sequential adjuvant chemotherapy and radiotherapy. Tumor recurrence occurred in 14 patients at a median duration of 10 months. The overall 2- and 5-year survival was 64% and 60%, respectively. The 2- and 5-year survival for stage I and II diseases was both 95%, while the 2-year survival for stage III and IV diseases was 25%. Patients who underwent sequential adjuvant therapy had an improved survival compared with patients who did not follow the protocol (P = 0.024). Our results with sequential adjuvant therapy are encouraging and justify future randomized trials.

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Prognostic nomogram for patients with non-metastatic HER2 positive breast cancer in a prospective cohort

The International Journal of Biological Markers ◽

10.1177/1724600818824786 ◽

2019 ◽

Vol 34 (1) ◽

pp. 41-46 ◽

Cited By ~ 2

Author(s):

Chuanxu Luo ◽

Xiaorong Zhong ◽

Zhu Wang ◽

Yu Wang ◽

Yanping Wang ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Prognostic Factors ◽

Prospective Cohort ◽

Proportional Hazard ◽

Her2 Positive ◽

Her2 Positive Breast Cancer ◽

Cox Proportional Hazard ◽

Cox Proportional Hazard Regression ◽

Positive Breast Cancer

Purpose: A nomogram is a reliable tool to generate individualized risk prediction by combining prognostic factors. We aimed to construct a nomogram for predicting the survival in patients with non-metastatic human epidermal growth factor receptor 2 (HER2) positive breast cancer in a prospective cohort. Methods: We analyzed 1304 consecutive patients who were diagnosed with non-metastatic HER2 positive breast cancer between January 2008 and December 2016 in our institution. Independent prognostic factors were identified to build a nomogram using the COX proportional hazard regression model. The prediction of the nomogram was evaluated by concordance index (C-index), calibration and subgroup analysis. External validation was performed in a cohort of 6379 patients from the Surveillance, Epidemiology, and End Results (SEER) database. Results: Through the COX proportional hazard regression model, five independent prognostic factors were identified. The nomogram predicting overall survival achieved a C-index of 0.78 in the training cohort and 0.74 in the SEER cohort. The calibration plot displayed favorable accordance between the nomogram prediction and the actual observation for 3-year overall survival in both cohorts. The quartiles of the nomogram score classified patients into subgroups with distinct overall survival. Conclusion: We developed and validated a novel nomogram for predicting overall survival in patients with non-metastatic HER2 positive breast cancer, which presented a favorable discrimination ability. This model may assist clinical decision making and patient–clinician communication in clinical practice.

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Mortality calculator as a possible prognostic predictor for overall survival after gastrectomy in elderly patients with gastric cancer

10.21203/rs.3.rs-37671/v1 ◽

2020 ◽

Author(s):

Hidenori Akaike ◽

Yoshihiko Kawaguchi ◽

Suguru Maruyama ◽

Katsutoshi Shoda ◽

Ryo Satio ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Prognostic Factors ◽

Elderly Patients ◽

Rank Test ◽

Proportional Hazard ◽

Mortality And Morbidity ◽

Neutrophil Lymphocyte Ratio ◽

Cox Proportional Hazard ◽

Long Term Follow Up

Abstract Background The number of elderly patients with gastric cancer (elderGC) has been increasing. Most of elderly patients were associated with reduced physiological functions, which sometimes constitute an obstacle to safe surgical treatments. The risk calculator of National Clinical Database (NRC), a Japanese surgical big database, provides mortality and morbidity as surgical-related risks. The purpose of this study is to investigate clinical significance of operative mortality calculated by NRC (NRC-mortality) during long-term follow-up after gastrectomy for elderGC.Methods We enrolled 73 patients aged 80 or over who underwent gastrectomy at our institution. Their surgical risk was evaluated based on the NRC-mortality. Several clinicopathological factors including NRC-mortality were selected and analyzed as possible prognostic factors for elderGC after gastrectomy. Statistical analysis was performing using the log-rank test and Cox proportional hazard model.Results NRC-mortality ranged 0.5 to 10.6%, and median value was 1.7%. Dividing elderGC into high- (1.7% or more, n=38) and low- (less than 1.7%, n=35) mortality groups, high-mortality group showed a significantly poor prognosis in overall survival (OS) than the low-mortality group, whereas there was no difference between the two groups in disease specific survival (DSS). In the analysis of Cox proportional hazard model, multivariate analysis revealed that NRC-mortality was an independent prognostic factor as well as neutrophil-lymphocyte ratio and surgical procedure in OS. In contrast, PS and pStage were independent prognostic factors in DSS, but not NRC-mortality.Conclusions The NRC-mortality might be clinical useful for not only predicting surgical mortality but also OS after gastrectomy in elderGC.

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Dementia and the Risk of Periodontitis: A Population-Based Cohort Study

Journal of Dental Research ◽

10.1177/00220345211037220 ◽

2021 ◽

pp. 002203452110372

Author(s):

K.S. Ma ◽

H. Hasturk ◽

I. Carreras ◽

A. Dedeoglu ◽

J.J. Veeravalli ◽

...

Keyword(s):

Cohort Study ◽

Relative Risk ◽

Propensity Score ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Rank Test ◽

Confounding Factors ◽

Proportional Hazard ◽

Cox Proportional Hazard ◽

Log Rank Test

Dementia and Alzheimer’s disease (AD) are proposed to be comorbid with periodontitis (PD). It is unclear whether PD is associated with dementia and AD independent of confounding factors. We aimed at identifying the relationship between the longitudinal risk of developing PD in a cohort of patients with dementia and AD who did not show any signs of PD at baseline. In this retrospective cohort study, 8,640 patients with dementia without prior PD were recruited, and 8,640 individuals without dementia history were selected as propensity score–matched controls. A Cox proportional hazard model was developed to estimate the risk of developing PD over 10 y. Cumulative probability was derived to assess the time-dependent effect of dementia on PD. Of the 8,640 patients, a sensitivity test was conducted on 606 patients with AD-associated dementia and 606 non-AD propensity score–matched controls to identify the impact of AD-associated dementia on the risk for PD. Subgroup analyses on age stratification were included. Overall 2,670 patients with dementia developed PD. The relative risk of PD in these patients was significantly higher than in the nondementia group (1.825, 95% CI = 1.715 to 1.942). Cox proportional hazard models showed that patients with dementia were more likely to have PD than individuals without dementia (adjusted hazard ratio = 1.915, 95% CI = 1.766 to 2.077, P < 0.0001, log-rank test P < 0.0001). The risk of PD in patients with dementia was age dependent ( P values for all ages <0.0001); younger patients with dementia were more likely to develop PD. The findings persisted for patients with AD: the relative risk (1.531, 95% CI = 1.209 to 1.939) and adjusted hazard ratio (1.667, 95% CI = 1.244 to 2.232; log-rank test P = 0.0004) of PD in patients with AD were significantly higher than the non-AD cohort. Our findings demonstrated that dementia and AD were associated with a higher risk of PD dependent of age and independent of systemic confounding factors.

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A Dynamic Prognostic Model To Predict Survival in Post-Polycythemia Vera Myelofibrosis.

Blood ◽

10.1182/blood.v110.11.2547.2547 ◽

2007 ◽

Vol 110 (11) ◽

pp. 2547-2547

Author(s):

Francesco F. Passamonti ◽

Elisa E. Rumi ◽

Marianna M. Caramella ◽

Chiara C. Elena ◽

Luca L. Arcaini ◽

...

Keyword(s):

Platelet Count ◽

Prognostic Factors ◽

Polycythemia Vera ◽

Median Survival ◽

Prognostic Model ◽

Time Dependent ◽

Proportional Hazard ◽

Cox Proportional Hazard ◽

Cox Proportional Hazard Regression

Abstract Polycythemia vera (PV) is a chronic myeloproliferative disorder with a propensity to develop myelofibrosis, a condition named post polycythemia vera myelofibrosis (post-PV MF). Survival and prognostic factors after transition to MF remain to be defined. We studied 68 patients with post-PV MF to define survival and prognostic factors for survival at diagnosis of post-PV MF. We also developed a dynamic prognostic model to predict survival at any time from diagnosis of post-PV MF. The median interval between the diagnosis of PV and that of post-PV MF was 13 years (range, 4–29.6 years). Patients with post-PV MF were observed for 181 person-years of follow-up. At diagnosis of post-PV MF, 43 (63%) of 68 patients had less than 65 years. During the follow-up, the incidence of thrombosis was 42 × 1000 person-years (95% CI: 19–93.5) and the incidence of leukemia was 50.3 × 1000 person-years (95% CI: 26–115). The median survival was 5.7 years. Multivariable Cox proportional hazard regression including age, hemoglobin value, platelet count, leukocyte count, and spleen size, showed that hemoglobin < 10 g/dL (P < .001) and platelet count < 100 × 109/L (P= .026) were independent risk factors for survival. We stratified patients at diagnosis of post-PV MF, according to these factors, obtaining two risk groups with significantly different survival (P = .003): low risk (Hb > 10 g/dL and platelet count > 100 × 109/L) with a median survival of 7 years, and high risk (Hb < 10 g/dL or platelet count < 100 × 109/L) with a median survival of 2 years. The prognostic model retained significance after adjustment for age in a multivariable Cox proportional hazard regression (HR: 4.3, 95% CI: 1.6–11.4; P= .003). To assess whether this prognostic model may predict survival at any time from diagnosis of post-PV MF, we evaluated in a time-dependent analysis 64 patients who had longitudinal blood cell counts during follow-up. As first step, we evaluated univariate survival analysis with hemoglobin value < 10 g/dL and platelet count < 100 ×109/L as time-dependent covariates. Both time-dependent parameters affected survival (HR for hemoglobin 5.8, 95% CI: 2.2–15.2, P < 0.001; HR for platelets 4.5, 95% CI: 1.67-12, P=.002). As second step, we evaluated the prognostic model assessed at diagnosis as time-dependent covariate, to define whether the acquisition of one risk factor during follow-up may affect survival. The HR was 7.5 (95% CI: 2.4-23.4; P < .001). The time-dependent prognostic model retained statistical significance after adjustment for age (P < .001). In conclusion, in patients developing post-PV myelofibrosis, a prognostic model based on hemoglobin level < 10 g/dL and platelet count < 100 × 109/L may predict survival at diagnosis of post-PV MF and at any time thereafter.

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A Comparison of Prognostic Models for Chronic Myelomonocytic Leukemia (CMML) in the Era of Hypomethylating Agents

Blood ◽

10.1182/blood.v120.21.1695.1695 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1695-1695 ◽

Cited By ~ 1

Author(s):

Eric Padron ◽

Najla H Al Ali ◽

Deniz Peker ◽

Jeffrey E Lancet ◽

Pearlie K Epling-Burnette ◽

...

Keyword(s):

Overall Survival ◽

Scoring System ◽

Prognostic Model ◽

Median Overall Survival ◽

Prognostic Score ◽

Risk Groups ◽

Prognostic Models ◽

Rank Test ◽

Log Rank Test ◽

Md Anderson

Abstract Abstract 1695 Introduction: CMML is a genetically and clinically heterogeneous malignancy characterized by peripheral monocytosis, cytopenias, and a propensity for AML transformation. Several prognostic models attempt to stratify patients into subcategories that are predictive for overall survival (OS), six models of which are specific to CMML. However, these models have either never been externally validated in the context of CMML or were externally validated prior to the use of hypomethylating agents. We externally validate and perform a detailed statistical comparison between the International Prognostic Scoring System (IPSS), MD Anderson Scoring System (MDASC), MD Anderson Prognostic Score (MDAPS), Dusseldorf Score (DS), and Spanish Scoring Systems (SS) in a large, single institution cohort. Methods: Data were collected retrospectively from the Moffitt Cancer Center (MCC) CMML database and charts were reviewed of patients that satisfied the WHO criteria for the diagnosis of CMML. The primary objective of the study was to validate the above prognostic models calculated at the time of initial presentation to MCC. All prognostic models were calculated as previously published. All analyses were conducted using SPSS version 15.0 (SPSS Inc, Chicago, IL). The Kaplan–Meier (KM) method was used to estimate median overall survival and the log rank test was used to compare KM survival estimates between two groups. Results: Between January 2000 and February 2012, 123 patients were captured by the MCC CMML database. The median age at diagnosis was 69 (30–90) years and the majority of patients were male (69%). By the WHO classification, the majority of patients had CMML-1 (84% vs. 16%) and most patients were subcategorized as MPN-CMML (59%) versus MDS-CMML (39%) by the FAB CMML criteria. The median overall survival of the entire cohort was 30 months and the rate of AML transformation was 44% (54). Twenty-two patients (18%) were treated with decitabine and 66 (54%) patients were treated with 5-azacitidine. Risk group stratification according to specific prognostic model is summarized in Table 1. The IPSS, MDASC, DS, and SS all predicted OS (p<0.05) while the MDASP could not be validated (p=0.924). When only patients who were treated with 5-azacitadine were considered, the MDASC, DS, and SS continued to predict OS (p<0.05) while the IPSS (p=0.15) and MDASP (p=0.239) did not. Previous reports have demonstrated that the MDASC provides further discrimination to refine stratification by the IPSS in Myelodysplastic Syndromes (MDS). Except for the low-risk DS patients, we grouped patients in our CMML cohort into lower and higher risk disease with each prognostic score and attempted to further stratify patients by the MDASC using KM and the log rank test. The MDASC was able to further risk stratify patients in each group for all prognostic models except those in the higher risk groups by the SS (p=0.07) and DS (P=0.45). When a similar statistical analysis was applied to each prognostic scoring system, only the MDASC was consistently able to further stratify the majority of risk groups as described in Table 2. The Dusseldorf scoring system was able to further stratify all lower risk groups regardless of model but was not able to do so in higher risk disease. Conclusions: This represents the first external validation of existing CMML prognostic models in the era of hypomethylating agent therapy. Except for the MDASP, we were able to validate the prognostic value all models tested. The MDASC represents the most robust model as it consistently refined the stratification of other models tested and remained predictive of OS in 5-azacitidine treated patients. Multi-institution collaboration is needed to construct a robust CMML specific prognostic model. Comparison to the IPSS-R is in progress. Disclosures: No relevant conflicts of interest to declare.

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