Thrombocytopenia at diagnosis adversely affects overall and leukemia-free survival in lower-risk MDS patients: A retrospective study from the FISiM registry
Abstract
Abstract Background Thrombocytopenia is a frequent hematologic abnormality in patients with myelodysplastic syndromes (MDS), occurring in approximately 40–60% of cases. It has been consistently associated with adverse clinical outcomes and is incorporated into the Revised International Prognostic Scoring System (IPSS-R), where platelet (PLT) counts <100,000/mm³ indicate a higher-risk disease category. In patients with lower-risk MDS (LR-MDS), the prognostic significance of thrombocytopenia is less well defined but has been incorporated in a prognostic model by the MD Anderson Cancer Center together with anemia, age, marrow blast percentage, and cytogenetic risk (Garcia-Manero G et al. Leukemia 2008). The objective of this study was to evaluate the prognostic impact of thrombocytopenia at diagnosis on overall survival (OS) and leukemia-free survival (LFS) in a large cohort of patients with LR-MDS enrolled in the registry of the Italian Foundation for the Study of Myelodysplastic Syndromes (FISiM). Methods We retrospectively analyzed clinical and hematologic data from patients diagnosed with LR-MDS between January 1, 2007, and October 29, 2024, and included in the nationwide FISiM registry. All patients were classified according to the 2016 WHO diagnostic criteria. Categorical variables were compared using the chi-square test. OS and LFS were estimated using the Kaplan-Meier method and compared by log-rank test. Cox proportional hazards regression models were used for multivariate analyses to identify variables independently associated with outcomes. A two-tailed p-value <0.05 was considered statistically significant. Results A total of 2,213 patients with LR-MDS were included in the analysis. Of these, 610 patients (27.6%) presented with PLT counts <100,000/mm³ at diagnosis, while 1,603 (72.4%) had counts ≥100,000/mm³. The cohort comprised 1,314 males and 899 females, with a median age of 75 years (range: 19–98). The median follow-up was 32.1 months. The overall median OS was 80.0 months, with 1-, 2-, and 3-year OS rates of 96%,87% and78%, respectively. According to WHO classification, MDS with multilineage dysplasia (MDS-MLD) was the most common subtype in the thrombocytopenic group (61% vs. 38%), followed by MDS with single-lineage dysplasia (15% vs. 28%). In univariate analysis, thrombocytopenia was significantly associated with inferior OS and LFS (p<0.001 for both comparisons). This finding was also correlated with low megakaryocyte cellularity and megakaryocytic dysplasia. Interestingly, thrombocytopenia was more frequently observed in patients with hemoglobin levels >10 g/dL, suggesting it may define a distinct biological subgroup. In multivariate analysis, PLT <100,000/mm³ remained an independent predictor of worse OS (hazard ratio [HR] 1.25; 95% confidence interval [CI]: 1.15–1.37; p<0.001), along with older age, female sex, hemoglobin <10 g/dL (all p<0.001), and marrow blasts ≥5% (p=0.003). Leukemic transformation occurred in 65 patients (10.7%) in the thrombocytopenic group and in 131 patients (8.2%) with PLT ≥100,000/mm³ (p=0.06). The median time to progression was significantly shorter in thrombocytopenic patients: 139.5 months (95% CI: 129.3–149.7) vs. 155.7 months (95% CI: 149.6–161.8); p=0.005. Overall, 723 patients (32.7%) died, with a higher mortality observed in the thrombocytopenic group (36.4% vs. 31.3%). In the multivariate analysis for LFS, PLT <100,000/mm³ remained an independent adverse factor (HR: 1.20; 95% CI: 1.02–1.40; p=0.03), together with female sex (p=0.003) and blast count ≥5% (p<0.001). Conclusions Our study confirms that thrombocytopenia at diagnosis is an independent predictor of worse overall and leukemia-free survival in patients with lower-risk MDS. These findings underscore the importance of incorporating platelet count into risk stratification strategies even within the LR-MDS population. Closer monitoring and potentially earlier therapeutic intervention should be considered in this subgroup to improve clinical outcomes.
Article Details
Authors (56)
Anna Calvisi
12Ospedale S. Francesco, SC Ematologia, CTMO e Laboratorio Specialistico, Nuoro, Italy
Rosangela Filiberti
2IRCS Ospedale Policlinico San Martino, Genova, Italy
Daniela Barraco
23ASST Sette Laghi, Varese, Italy
Massimo Bernardi
Isabella Capodanno
8SOC Ematologia Azienda USL-IRCSS di Reggio Emilia, Reggio Emilia, Italy
Andrea Castelli
11Ospedale di Circolo e Fondazione Macchi - ASST Settelaghi, Università degli Studi dell'Insubria, S.C. Ematologia, Varese, Italy
Rosanna Ciancia
25IRCCS Centro di Riferimento Oncologico (CRO), Aviano, Italy
Carmen Fava
2Università degli studi di Torino, Dipartimento di Scienze Cliniche e Biologiche, torino, Italy
Carla Fili
9Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), PO “S.Maria della Misericordia”, SOC Clinica Ematologica, Centro Trapianti e Terapie Cellulari, Udine, Italy
Chiara Frairia
7AOU Città della Salute e della Scienza di Torino, Ospedale Molinette, Torino, Italy
Francesco Frattini
11ASST di Mantova - Ospedale “Carlo Poma”, Mantova, Italy
Piero Galieni
9Ospedale C.e G. Mazzoni, U.O.C. di Ematologia, Ascoli Piceno, Italy
Pasquale Niscola
4S.Eugenio Hospital, ASL Roma 2, Hematology Unit, Rome, Italy
Stefania Paolini
2IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli”, Bologna, Italy
Andrea Patriarca
Therapeutic Innovation in Hematology, Hematology Unit, Azienda Ospedaliero-Universitaria Maggiore della Carità, Novara, Italy
Anna Maria Pelizzari
16ASST - Spedali Civili, Brescia, Italy
Grazia Sanpaolo
15IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
Carmine Selleri
Francesco Alesiani
NEC Laboratories Europe GmbH , Kurfürsten-Anlage 36, 69115 Heidelberg,
Gianni Binotto
5Department of Medicine, Hematology Unit, University of Padova, Padova, Italy
Costanza Bosi
21Diipartimento Oncologia -Ematologia, Divisione di Ematologia, Piacenza, Italy
Catello Califano
29Hematology, Hospital “Andrea Tortora”, Pagani, Pagani, Italy
Barbara Castagnari
1AUSL ROMAGNA, Hematology Unit & Romagna Transplant Network, Ravenna, Italy
Elena Crisa
2Candiolo Cancer Institute, Hematology Division, Candiolo, Italy
Monica Crugnola
Marco De Gobbi
26San Luigi Gonzaga Hospital, Department of Clinical and Biological Sciences, Orbassano(To), Italy
Matteo Della Porta
1IRCCS Humanitas Research Hospital, AI Center, Rozzano, Italy
Nicola Di Renzo
Dario Ferrero
29AOU Città della Salute e della Scienza, SC Ematologia, Torino, Italy
Carlo Finelli
10IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
Carla Foli
31ASLTO4 ospedale Evangelico Valdese, SDD Ematologia, Torino, Italy
Claudio Fozza
20University of Sassari, Sassari, Italy
Maurizio Frezzato
33Ospedale San Bortolo, UOC Ematologia -, Vicenza, Italy
Ferdinando Frigeri
30AORN S. Anna e S. Sebastiano, Caserta, Italy
Gianluca Guaragna
35Ospedale A. Perrino, Unità Operativa Complessa di Ematologia -, Brindisi, Italy
Monia Marchetti
15Azienda Ospedaliera Universitaria di Alessandria, Alessandria, Italy
Daniele G. Mattei
13SC Ematologia, Azienda Ospedale Santa Croce e Carle, Cuneo, Italy
Mara Memoli
25Federico II University Medical School, Department of Hematology, Naples, Italy
Paola Minetto
12Clinic of Hematology, Department of Internal Medicine, University of Genova, Genova, Italy
Alfredo Molteni
9ASST di Cremona, Cremona, Italy
Pellegrino Musto
17Unità di Ematologia e Trapianto di Midollo Osseo, AOUC Policlinico, Bari, Italy
Esther Natalie Oliva
29London North West University Healthcare NHS Trust, Hematology Department, London, United Kingdom
Giuseppe Alberto Palumbo
43AOU Policlinico “G. Rodolico” - San Marco, UOC Ematologia, Catania, Italy
Fabrizio Pane
4Hematology – Department of Clinical Medicine and Surgery, University Hospital “Federico II”, Napoli, Italy
Giuseppe Pietrantuono
32IRCCS CROB, Referral Cancer Center of Basilicata, Rionero In Vulture, Italy
Federica Pilo
6Azienda Ospedaliera Brotzu, Cagliari, Italy
Antonella Poloni
1Hematology Unit, Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, Ancona, Italy
Giulia Rivoli
1Ospedale Policlinico San Martino IRCCS, Genova, Italy
Mariarita Sciumè
8Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
Rodolfo Tassara
50S.C. Medicina interna 2 P.O. Levante Ospedale di Cairo Montenotte, Sc Medicina interna, Savona, Italy
Mauro Turrini
13Ospedale Classificato Valduce, Como, Italy
Letizia Zannoni
52Ospedale degli Infermi AUSL Romagna, UO Ematologia, Rimini, Italy
Ilaria Naldi
34FISiM, Bologna, Italy
Enrico Balleari
18IRCCS Ospedale Policlinico San Martino, Genova, Italy
Valeria Santini
7DMSC University of Florence, AOUC, MDS Unit, Hematology, Florence, Italy
Francesco Onida
22ASST Fatebenefratelli-Sacco, University Milan, Milan, Italy