Clinical and Genomic-Based Decision Support System to Define the Optimal Timing of Allogeneic Hematopoietic Stem-Cell Transplantation in Patients With Myelodysplastic Syndromes
Authors: Tentori Cristina Astrid , Gregorio Caterina , Robin Marie , Gagelmann Nico , Gurnari Carmelo , Ball Somedeb , Caballero Berrocal Juan Carlos , Lanino Luca , D'Amico Saverio , Spreafico Marta , Maggioni Giulia , Travaglino Erica , Sauta Elisabetta , Meggendorfer Manja , Zhao Lin-Pierre , Campagna Alessia ,   GenoMed4All, Synthema, GESMD, FISIM, and EuroBloodNET, Savevski Victor , Santoro Armando , Al Ali Najla , Sallman David , Sole Francesc , Garcia-Manero Guillermo , Germing Ulrich , Kroger Nicolaus , Kordasti Shahram , Santini Valeria , Sanz Guillermo , Kern Wolfgang , Platzbecker Uwe , Diez-Campelo Maria , Maciejewski Jaroslaw P. , Ades Lionel , Fenaux Pierre , Haferlach Torsten , Zeidan Amer M. , Castellani Gastone , Komrokji Rami , Ieva Francesca , Della Porta Matteo Giovanni , Bernardi Massimo , Di Grazia Carmen , Vago Luca , Rivoli Giulia , Borin Lorenza , Chiusolo Patrizia , Giaccone Luisa , Voso Maria Teresa , Bewersdorf Jan Philipp , Nibourel Olivier , Beyá Marina Díaz , Jerez Andrés , Hernández Francisca , Kennedy Kyra Velázquez , Xicoy Blanca , Ubezio Marta , Russo Antonio , Todisco Gabriele , Mannina Daniele , Bramanti Stefania , Zampini Matteo , Riva Elena , Bicchieri Marilena , Asti Gianluca , Viviani Filippo , Buizza Alessandro , Tinterri Benedetta , Kubasch Anne-Sophie , Bacigalupo Andrea , Raiola Anna Maria , Rambaldi Alessandro , Passamonti Francesco , Ciceri Fabio 
Published: May 2024

PURPOSE Allogeneic hematopoietic stem-cell transplantation (HSCT) is the only potentially curative treatment for patients with myelodysplastic syndromes (MDS). Several issues must be considered when evaluating the benefits and risks of HSCT for patients with MDS, with the timing of transplantation being a crucial question. Here, we aimed to develop and validate a decision support system to define the optimal timing of HSCT for patients with MDS on the basis of clinical and genomic information as provided by the Molecular International Prognostic Scoring System (IPSS-M). PATIENTS AND METHODS We studied a retrospective population of 7,118 patients, stratified into training and validation cohorts. A decision strategy was built to estimate the average survival over an 8-year time horizon (restricted mean survival time [RMST]) for each combination of clinical and genomic covariates and to determine the optimal transplantation policy by comparing different strategies. RESULTS Under an IPSS-M based policy, patients with either low and moderate-low risk benefited from a delayed transplantation policy, whereas in those belonging to moderately high-, high- and very high-risk categories, immediate transplantation was associated with a prolonged life expectancy (RMST). Modeling decision analysis on IPSS-M versus conventional Revised IPSS (IPSS-R) changed the transplantation policy in a significant proportion of patients (15% of patient candidate to be immediately transplanted under an IPSS-R–based policy would benefit from a delayed strategy by IPSS-M, whereas 19% of candidates to delayed transplantation by IPSS-R would benefit from immediate HSCT by IPSS-M), resulting in a significant gain-in-life expectancy under an IPSS-M–based policy ( P = .001). CONCLUSION These results provide evidence for the clinical relevance of including genomic features into the transplantation decision making process, allowing personalizing the hazards and effectiveness of HSCT in patients with MDS.