Validation of the revised International Prognostic Scoring System in treated patients with myelodysplastic syndromes.

The International Prognostic Scoring System (IPSS) was recently revised (IPSS-R) under the auspices of the MDS Foundation as a collaborative international effort to refine its prognostic power. Our purpose was to externally validate this new risk model using a large single-institution cohort, determine its prognostic power in patients receiving active treatment, and explore its utility in guiding therapeutic decisions. Data were collected retrospectively from our myelodysplastic syndrome (MDS) database and verified by chart review. Of the data available for 1,088 patients, 152 (14%), 353 (32%), 237 (22%), 190 (18%), and 156 (14%) patients were classified as very low, low, intermediate, high, and very high risk, respectively, with median overall survival (OS) of 90 (95%CI 71-109), 54 (95%CI 50-59), 34 (95%CI 26-43), 21 (95%CI 17-25), and 13 months (95%CI 11-15), respectively (P < 0.005). We found that the IPSS-R further refined prognostic discrimination in all IPSS risk categories, particularly in the intermediate 1 and 2 groups. Among high and very high IPSS-R patients receiving azacitidine, OS was significantly improved versus patients not receiving azacitidine, with corresponding median OS of 25 versus 18 months (P = 0.028) and 15 versus 9 months (P = 0.005), respectively. Similarly, patients with IPSS-R high- and very high-risk disease who underwent allogeneic hematopoietic stem cell transplantation had significantly improved OS versus nontransplant approaches (P < 0.005). High and very high IPSS-R patients derived a survival advantage from disease-modifying therapies. Our data validate the prognostic value of the proposed IPSS-R and show that its refined IPSS prognostic discrimination can be applied to actively treated patients.

Validation of the MD Anderson Prognostic Risk Model for patients with myelodysplastic syndrome.

BACKGROUND: The proposed MD Anderson Risk Model Score (MDAS) for myelodysplastic syndromes (MDS) refines outcome discrimination compared with the International Prognostic Scoring System (IPSS). We applied the MDAS to Moffitt Cancer Center (MCC) MDS patients to validate its prognostic utility. METHODS: This was a retrospective analysis of MDS cases, as defined by World Health Organization criteria, from the Moffitt database, with confirmatory chart review. RESULTS: A total of 775 patients evaluated between January 2001 and December 2009 were included. Patients were reclassified by MDAS as low (20.6%), intermediate-1 (31%), intermediate-2 (21%), high risk (16.1%), and unknown (11.2%). Median overall survival (OS) from diagnosis was 92, 49, 27, and 14 months for low, intermediate-1, intermediate-2, and high-risk MDAS groups, respectively (P < .005). Median OS from referral was 61, 28, 15, and 8 months (P < .005), respectively. Among 484 patients classified by IPSS as low or intermediate-1 risk, 25% were up-staged as intermediate-2 or high risk by MDAS; 4 prognostically distinct subgroups were identified among lower risk IPSS categories with median OS of 93, 53, 31, and 18 months (P < .005). Among 201 intermediate-2 or high-risk IPSS patients, 15.4% were down-staged to intermediate-1 by MDAS, with 3 groups identified by MDAS having median OS of 33, 23, and 14 months. Acute myeloid leukemia transformation rate was highest among high-risk MDAS (50.4%). In Cox regression analysis, higher risk MDAS predicted inferior OS (hazard ratio 1.42; P < .005) independent of IPSS. CONCLUSIONS: Our data validated MDAS' prognostic value. MDAS is complementary to IPSS and refines prognostic precision.

Hypoalbuminemia is an independent prognostic factor for overall survival in myelodysplastic syndromes.

We hypothesized that hypoalbuminemia is an independent prognostic factor in patients with myelodysplastic syndromes (MDS). We analyzed records of 767 patients treated at Moffitt Cancer Center between January 2001 and December 2009 to evaluate the relationship between serum albumin (SA) at the time of presentation and overall survival (OS). Patients (median age of 69 years) were stratified into three groups based on SA concentration (≤3.5, 3.6-4.0, and >4.0 g/dL). Two-thirds of the patients had low or intermediate-1 International Prognostic Scoring System (IPSS)-based risk for MDS. Median OS by SA concentration of ≤3.5, 3.6-4.0, and >4.0 g/dL was 11, 23, and 34 months, respectively (P < 0.005), whereas rate of acute myeloid leukemia progression was highest in patients with low SA (≤3.5 g/dL). The SA level offered prognostic discrimination for outcomes within the lower and higher IPSS risk groups, as well as with the MD Anderson risk model. In multivariable analysis, SA was a significant independent co-variate for OS after adjustment for IPSS, age, serum ferritin, and transfusion dependence (hazard ratio = 0.8; 95% CI 0.6-0.9; P = 0.004). Our findings indicate that hypoalbuminemia is an independent prognostic biomarker that may serve as a surrogate representative of disease biology or comorbidities in patients with MDS.

Validation of the Lower-Risk MD Anderson Prognostic Scoring System for Patients With Myelodysplastic Syndrome.

The International Prognostic Scoring System (IPSS) is the most widely used tool for risk assessment and treatment decisions for myelodysplastic syndrome (MDS). Several new models have been proposed to identify a subset of lower-risk patients with MDS who are experiencing inferior than expected outcomes. We validated the Lower-Risk MD Anderson Risk Model (LR-MDAS) in 1288 lower-risk patients with MDS by the IPSS. On the basis of the LR-MDAS, 228 patients (17%) were in category 1, 730 patients (57%) were in category 2, 315 patients (25%) were in category 3, and 15 patients (1%) were in an unknown category. The median overall survival for the corresponding LR-MDAS categories was (1) 109 months (95% confidence interval [CI], 82-137), (2) 56 months (95% CI, 58-73), and (3) 29 months (95% CI, 24-35) (P < .005). Overall, 25% of patients were upstaged to category 3. LR-MDAS refined prognostic value among very low-, low-, and intermediate-risk Revised IPSS. The rate of acute myeloid leukemia transformation according to LR-MDAS was 15%, 18%, and 29% for categories 1, 2, and 3, respectively (P < .005). Our data validate the prognostic value of the LR-MDAS model, but the utility of it as a treatment decision tool should be studied prospectively.

Impact of tobacco usage on disease outcome in myelodysplastic syndromes.

We hypothesized that tobacco usage is an independent prognostic factor in patients with myelodysplastic syndromes (MDS). To evaluate the impact of tobacco usage in this population, we identified patients diagnosed with MDS in our Center's MDS database and reviewed individual charts retrospectively. Of the 767 MDS patients identified, 743 patients (97%) had a known tobacco usage history. Given that the majority of tobacco users were smokers, we stratified patients as having never smoked (never-smoker group) versus current or former smokers (ever-smoker group). Greater than 60% of ever-smokers were risk stratified as having low or intermediate-1 (int-1) risk at diagnosis based on the International Prognostic Scoring System for MDS. In patients with lower-risk MDS, we found that ever-smokers had an increased proportion of poor-risk karyotypes (8.8%) compared with never-smokers (2.4%) (P=0.003). The adverse effect of smoking was greatest in the low-risk and int-1-risk groups, where median overall survival was 69 months (95% CI 42-96) in never-smokers versus 48 months (95% CI 41-55) in ever-smokers (P=0.006). The median overall survival for never-smokers, former smokers, and current smokers was 69 months (95% CI 42-96), 50 months (95% CI 43-57), and 38 months (95% CI 23-53), respectively, in patients risk stratified as lower-risk MDS (P=0.01). Our findings suggest that tobacco usage negatively impacts overall survival in patients with lower-risk MDS.