A Prognostic Model of Therapy-Related Myelodysplastic Syndrome for Predicting Survival and Transformation to Acute Myeloid Leukemia

Abstract

Background We evaluated the characteristics of a cohort of patients with therapy-related myelodysplastic syndrome (t-MDS) to create a prognostic model. Patients and Methods We identified 281 patients with MDS that had received prior chemotherapy and/or radiotherapy for prior malignancy. Potential prognostic factors were determined by univariate and multivariate analysis. Results Multivariate Cox regression analysis identified 7 factors that independently predicted short survival in t-MDS: age ≥65 years (HR=1.63), ECOG performance status 2–4 (HR=1.86), poor cytogenetics (−7 and/or complex; HR=2.47), WHO MDS subtype (RARs or RAEB-1/2; HR=1.92), hemoglobin (<11g/dL; HR=2.24), platelets (<50×109/dL; HR=2.01), and transfusion dependency (HR=1.59). These risk factors were used to create a prognostic model that segregated patients into three groups with distinct median overall survival: good (0–2 risk factors; 34 months), intermediate (3–4 risk factors; 12 months) and poor (5–7 risk factors; 5 months) (p<0.001) and 1-year leukemia free survival (96%, 84%, and 72%, respectively, p=0.003). This model also identified distinct survival groups according to t-MDS therapy. Conclusion In summary, we devised a prognostic model specifically for patients with t-MDS that predicts overall survival and leukemia-free survival. This model may facilitate the development of risk-adapted therapeutic strategies.

Therapy-related myelodysplastic syndromes, or are they?

“…Specifically, the median OS for t-MDS was recently reported to be around 16 months [7]. However it is important to recognize the significant heterogeneity in clinical outcomes of patients with t-MDS, with a subset of patients having a more indolent course [7,94]. These patients might not benefit from aggressive therapeutic interventions, highlighting the importance of accurate risk stratification for patients with t-MDS.…”

“…Recently the MD Anderson group devised a prognostic model specifically for patients with t-MDS, t-MDS Prognostic Scoring System (TPSS) [94]. However most of the patients in this database were not treated with allogeneic hematopoietic cell transplantation (HCT) and it was externally validated in azacitidine-treated patients only [100].…”

The evolving field of prognostication and risk stratification in MDS: Recent developments and future directions

“…Based on 7 variables, patients are divided into three prognostic groups [ Table 1]. Creating a scoring system specifically for t-MDS is important since this population was excluded from development of the IPSS, IPSS-R, and WPPS, and may be less responsive to standard therapies compared to those with de novo MDS [41,42]. This prognostic score nonetheless requires further validation.…”

“…A third prognostic model was developed by the MD Anderson group (the treatment-related MDS Prognostic Scoring System [T-PSS]) specifically for patients with t-MDS using data from 281 patients with t-MDS, defined as those who have received chemotherapy or radiation for treatment of malignancy [41]. The 2008 WHO classification includes this group of patients under the entity of therapy-related myeloid neoplasm (t-MN) [19].…”

“…[24]), T-PSS: Treatment-related MDS Prognostic Scoring System (ref. [41]), and FPSS: French Prognostic Scoring System (ref. [105] prognostic schemes divide patients into risk groups [ Table 1], though each of these tools has inherent limitations.…”