A WHO Classification-Based Prognostic Scoring System (WPSS) for Predicting Survival in Myelodysplastic Syndromes.
Authors: Malcovati Luca , Germing Ulrich , Kuendgen Andrea , Della Porta Matteo G. , Invernizzi Rosangela , Giagounidis Aristoteles , Hildebrandt Barbara , Bernasconi Paolo , Knipp Sabine , Lazzarino Mario , Strupp Corinna , Cazzola Mario 
Published: April 2020

Abstract
The WHO classification of myelodysplastic syndromes (MDS) is based on uni- or multi-lineage hematopoietic involvement, blast count and cytogenetic features. We recently confirmed the prognostic value of this classification and demonstrated that cytogenetics and transfusion requirement are the main prognostic factors affecting survival of WHO subgroups (JCO 2005, in the press). The aim of the present study was to define and validate a scoring system for evaluating prognosis in MDS classified according to WHO criteria. The patients comprised a learning cohort, in whom investigations were aimed at defining the set of variables to be included in the prognostic model and their weighted scores, and a validation cohort, in whom we evaluated whether the prognostic value of the scoring system was confirmed. The learning cohort was formed of 467 consecutive patients with a diagnosis of de novo MDS made at the IRCCS Policlinico S. Matteo, Italy, between 1992 and 2002, while the validation cohort consisted of 620 consecutive patients diagnosed at the Heinrich-Heine-University Hospital between 1982 and 2003. All cases were reclassified by independent cytologists according to the WHO criteria. Those patients who were treated with allogeneic stem cell transplantation or chemotherapy, were censored at the time of this therapeutic intervention. Uni- and multivariate analyses were performed by means of Cox proportional hazards regression. The actuarial probabilities of overall survival (OS) and leukemia-free survival (LFS) were estimated using the Kaplan-Meier product limit method. Based on the results of the uni- and multivariate analyses, the most significant variables selected for the prognostic model were WHO subgroups, cytogenetic abnormalities scored according to the IPSS and transfusion requirement. Risk scores for each variable were estimated based on coefficients from the proportional hazards regression (Table 1).
Table 1 - WHO-Classification Based Prognostic Scoring System (WPSS) for MDS Prognostic variable Score value 0 1 2 3 WHO category RA, RARS, 5q- RCMD, RCMD-RS RAEB-1 RAEB-2 Karyotype Good Intermediate Poor - Transfusion requirement No Regular - -
By summing the score values for the three variables, patients were stratified into five distinct risk groups [very low (score 0), low (1), intermediate (2), high (3–4), very high (5–6)], showing significantly different OS and probability of leukemia evolution (P&lt;.0001). The scoring system was then evaluated in the independent cohort of patients in order to confirm its prognostic value. In this validation cohort, the WPSS groups showed significantly different OS (P&lt;.0001), the median survival in the five risk groups being 136, 63, 44, 19 and 8 months, respectively. The WPSS groups also showed significantly different probabilities of leukemia progression (P&lt;.0001), ranging from a 10-year probability of 7% in the very low risk group to a 50% probability of leukemia evolution reached at 8 months in the very high risk group. In conclusion, we have defined a prognostic scoring system based on WHO subgroups, cytogenetics and transfusion requirement. WPSS improves the capacity of the WHO classification to stratify OS and LFS of MDS patients and therefore may be a useful tool for clinical decision-making.