Thrombocytopenia at diagnosis adversely affects overall and leukemia-free survival in lower-risk MDS patients: A retrospective study from the FISiM registry

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.

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Blood
Published
2025-11-03
DOI
https://doi.org/10.1182/blood-2025-2080
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Acute Myeloid Leukemia Research
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article

Thrombocytopenia at diagnosis adversely affects overall and leukemia-free survival in lower-risk MDS patients: A retrospective study from the FISiM registry

Esther Natalie Olíva, Stefania Paolini, Ilaria Naldi, Rodolfo Tassara et al.
Blood
Acute Myeloid Leukemia Research
article

Thrombocytopenia at diagnosis adversely affects overall and leukemia-free survival in lower-risk MDS patients: A retrospective study from the FISiM registry

Esther Natalie Olíva, Stefania Paolini, Ilaria Naldi, Rodolfo Tassara, Rosangela Filiberti, Alfredo Molteni, Daniele Giovanni Mattei, Chiara Frairia, Isabella Capodanno, Marco Gobbi, Monica Crugnola, Claudio Fozza, Nicola Di Renzo, Federica Pilo, Enrico Balleari, Costanza Bosi, Giuseppe Pietrantuono, Dario Ferrero, Daniela Barraco, Mauro Turrini, Carmine Selleri, Anna Maria Pelizzari, Andrea Patriarca, Grazia Sanpaolo, Elena Crisà, Rosanna Ciancia, Mara Memoli, Pellegrino Musto, Fabrizio Pane, Mariarita Sciumé, Francesco Onida, Francesco Alesiani, Massimo Bernardi, Pasquale Niscola, Paola Minetto, Piero Galieni, Cristina Foli, Carlo Finelli, Francesco Frattini, Ferdinando Frigeri, Giuseppe Alberto Palumbo, Gianni Binotto, Monia Marchetti, Giulia Rivoli, Maurizio Frezzato, Catello Califano, Letizia Zannoni, Anna Calvisi, Antonella Poloni, Matteo Giovanni Della Porta, Andrea Castelli, Valeria Santini, Barbara Castagnari, Carmen Fava, Gianluca Guaragna, Carla Filì
article en

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.

BloodVol. 146(Supplement 1)
National Agency for New Technologies, Energy and Sustainable Economic Development (IT), Marche Polytechnic University (IT), Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT), University of Padua (IT), University of Sassari (IT), Casa Sollievo della Sofferenza (IT), London North West Healthcare NHS Trust (GB), Ospedale di Circolo e Fondazione Macchi (IT), CTO Hospital (IT), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT), Ospedale Maggiore (IT), Azienda Sanitaria Unità Locale di Reggio Emilia (IT), Centro di Riferimento Oncologico della Basilicata (IT), L'organizzazione Ospedale di Civitanova M (IT), Fondazione Ricerca Molinette (IT), IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT), Italian Foundation of Myelodysplastic Syndromes (IT), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), Ospedale A. Perrino (IT), Azienda Unità Sanitaria Locale Della Romagna (IT), CTO Andrea Alesini (IT), Federico II University Hospital (IT), Istituto di Ematologia di Bologna (IT), Azienda USL di Bologna (IT), Azienda Ospedaliero Universitaria Maggiore della Carita (IT), Presidio Ospedaliero (IT), Azienda Ospedaliera S.Maria (IT), National Cancer Institute (UA), Ospedale Santa Maria della Misericordia di Udine (IT), Azienda Sanitaria Locale Alessandria (IT), A. O. Ordine Mauriziano di Torino (IT), Ospedale Infermi di Rimini (IT), Policlinico Universitario di Catania (IT), IRCCS Ospedale San Raffaele (IT), Ospedali Riuniti San Giovanni di Dio e Ruggi d'Aragona (IT), Ospedale di Parma (IT), Azienda Sanitaria Ospedaliera S.Croce e Carle Cuneo (IT), St. Eugenio Hospital (IT), Associazione Italiana Ematologia Oncologia Pediatrica (IT), Azienda Ospedaliera Ospedale Maggiore (IT), Ospedale Policlinico San Martino (IT), Ospedale Sant'Anna (IT), Candiolo Cancer Institute (IT), Ospedale San Bortolo (IT), Ospedale degli Infermi (IT), Ospedale Vito Fazzi (IT), Ospedale San Luigi Gonzaga (IT), ASST Fatebenefratelli Sacco (IT), Ospedale Valduce (IT), Ospedale Civile di Giaveno (IT), IRCCS Humanitas Research Hospital (IT), Azienda Ospedaliera Carlo Poma (IT), Istituti Ospitalieri di Cremona (IT), University of Florence (IT), University of Bari Aldo Moro (IT), University of Naples Federico II (IT)
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