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Time-Dependent Prognostic Scoring System for Predicting Survival and Leukemic Evolution in Myelodysplastic Syndromes

Luca Malcovati, Ulrich Germing, Andrea Kuendgen, Matteo G. Della Porta, Cristiana Pascutto, Rosangela Invernizzi, Aristoteles Giagounidis, Barbara Hildebrandt, Paolo Bernasconi, Sabine Knipp, Corinna Strupp, Mario Lazzarino, Carlo Aul, Mario Cazzola

From the Departments of Hematology and Medicine, University of Pavia & Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy; Departments of Hematology, Oncology, and Clinical Immunology and Human Genetics, Heinrich-Heine-University, Düsseldorf; and Department of Haematology, Oncology, and Clinical Immunology, St Johannes Hospital, Duisburg, Germany

Address reprint requests to Mario Cazzola, MD, Department of Hematology, University of Pavia, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, 27100 Pavia, Italy; e-mail: mario.cazzola{at}unipv.it

Purpose The aims of this study were to identify the most significant prognostic factors in myelodysplastic syndromes (MDS) taking into account both their values at clinical onset and their changes in time and to develop a dynamic model for predicting survival and leukemic evolution that can be applied at any time during the course of the disease.

Patients and Methods We studied a learning cohort of 426 MDS patients diagnosed at the Department of Hematology, San Matteo Hospital, Pavia, Italy, between 1992 and 2004, and a validation cohort of 739 patients diagnosed at the Heinrich-Heine-University Hospital, Düsseldorf, Germany, between 1982 and 2003. All patients were reclassified according to WHO criteria. Univariable and multivariable analyses were performed using Cox models with time-dependent covariates.

Results The most important variables for the prognostic model were WHO subgroups, karyotype, and transfusion requirement. We defined a WHO classification–based prognostic scoring system (WPSS) that was able to classify patients into five risk groups showing different survivals (median survival from 12 to 103 months) and probabilities of leukemic evolution (P < .001). WPSS was shown to predict survival and leukemia progression at any time during follow-up (P < .001), and its prognostic value was confirmed in the validation cohort.

Conclusion WPSS is a dynamic prognostic scoring system that provides an accurate prediction of survival and risk of leukemic evolution in MDS patients at any time during the course of their disease. This time-dependent system seems particularly useful in lower risk patients and may be used for implementing risk-adapted treatment strategies.

Supported by grants from Associazione Italiana per la Ricerca sul Cancro, Milan; Fondazione Cariplo, Milan; Fondazione Ferrata Storti, Pavia; and Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy (M.C.); from Kompetenznetz "Akute und Chronische Leukämien" des Bundesforschungsministerium (U.G.); Bundesministerium für Bildung und Forschung, Competence Network (C.A.); and from Piano Regionale Sangue 2006, Regione Lombardia, Milan, Italy (M.L.).

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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Related Correspondence

• Time-Dependent Prognostic Scoring System for Myelodysplastic Syndromes Has Significant Limitations That May Influence Its Reproducibility and Practical Application
  David T. Bowen, Pierre Fenaux, Eva Hellstrom-Lindberg, and Theo de Witte
  JCO 2008 26: 1180 [Full Text]

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