Incorporation of molecular data into the Revised International Prognostic Scoring System in treated patients with myelodysplastic syndromes

Abstract

The Revised International Prognostic Scoring System (IPSS-R) was developed for untreated myelodysplastic syndrome (MDS) patients based on clinical data. We created and validated a new model that incorporates mutational data to improve the predictive capacity of the IPSS-R in treated MDS patients. Clinical and mutational data from treated MDS patients diagnosed between January 2000 and January 2012 were used to develop the new prognostic system. A total of 508 patients were divided into training (n=333) and validation (n=175) cohorts. Independent significant prognostic factors for survival included age, IPSS-R, EZH2, SF3B1 and TP53. Weighted coefficients for each factor were used to build the new linear predictive model, which produced four prognostic groups: low, intermediate-1, intermediate-2 and high with a median overall survival of 37.4, 23.2, 19.9 and 12.2 months, respectively, P<0.001. Significant improvement in the C-index of the new model (0.73) was observed compared with the IPSS-R (0.69). The new model predicted outcome both in a separate validation cohort and in another cohort of patients with paired samples at different time points during their disease course. The addition of mutational data to the IPSS-R makes it dynamic and enhances its predictive ability in treated MDS patients regardless of their initial or subsequent therapies.

Single-nucleotide polymorphism array (SNP-A) improves the identification of chromosomal abnormalities by metaphase cytogenetics in myelodysplastic syndrome

“…Nazha and colleagues25 demonstrated a new model that incorporates mutational data to improve the predictive capacity of the IPSS-R in 508 treated MDS patients, and independent prognostic factors for survival included age, IPSS-R, EZH2, SF3B1 and TP53 mutations.…”

Implications of molecular genetic diversity in myelodysplastic syndromes

“…(4, 17) The disadvantage to this approach is its complexity, which could represent a barrier to adoption. It also may not consider subtleties that might limit its prognostic accuracy.…”

Hypomethylating agents (HMA) treatment for myelodysplastic syndromes: alternatives in the frontline and relapse settings

“…These models are prognostic tools at diagnosis when used for de novo disease or when patients have not undergone a single line of therapy. However, this does not reflect treatment approaches for the majority of MDS patients in the era of modern therapy, particularly as molecular abnormalities are increasingly identified and used for prognosis and treatment determination [3, 22]. Additionally, none of the aforementioned scoring systems address patient related factors such as comorbidities, which have a significant independent impact on survival and prognostic scores [12, 23].…”