Clinical, histopathological and molecular characterization of hypoplastic myelodysplastic syndrome

• Published in: Leukemia Vol. 33; no. 10; pp. 2495 - 2505
• Main Authors: Bono, Elisa, McLornan, Donal, Travaglino, Erica, Gandhi, Shreyans, Gallì, Anna, Khan, Alesia Abigael, Kulasekararaj, Austin G., Boveri, Emanuela, Raj, Kavita, Elena, Chiara, Ireland, Robin M., Bianchessi, Antonio, Jiang, Jie, Todisco, Gabriele, Ferretti, Virginia Valeria, Cazzola, Mario, Marsh, Judith. C. W., Malcovati, Luca, Mufti, Ghulam J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2019; Nature Publishing Group
• Subjects: 45; 45/23; 45/70; 692/308/2056; 692/699/1541/1990/1673; Abnormalities; Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Anemia, Aplastic - pathology; Aplastic anemia; Bone marrow; Bone Marrow - pathology; Cancer Research; Chromosome Aberrations; Cohort Studies; Critical Care Medicine; Development and progression; Diagnosis, Differential; Diagnostic systems; Differential diagnosis; Female; Gene mutations; Genetic aspects; Health aspects; Hematology; Humans; Intensive; Internal Medicine; Karyotyping; Leukemia research; Male; Medicine; Medicine & Public Health; Middle Aged; Mutation; Myelodysplastic syndrome; Myelodysplastic syndromes; Myelodysplastic Syndromes - pathology; Oncology; Young Adult; Italy
• ISSN: 0887-6924; 1476-5551; 1476-5551
• DOI: 10.1038/s41375-019-0457-1

Diagnostic criteria for hypoplastic myelodysplasic syndrome (h-MDS) have not been clearly established, making the differential diagnosis from other bone marrow failure syndromes (BMF) challenging. In this study, we aimed to delineate clinical, histopathological, and molecular features of h-MDS, based on a large and well-annotated cohort of patients with bone marrow (BM) hypocellularity. The study included 534 consecutive adult patients with hypocellular BM (278 h-MDS and 136 aplastic anemia), and 727 with normo- or hypercellular MDS (n-MDS). Comparison of clinical features of patients with h-MDS as defined by BM cellularity ≤25% ( n  = 204) or reduced age-adjusted cellularity ( n  = 74) did not reveal significant differences. We developed a diagnostic score to discriminate h-MDS from non-malignant BMF based on histological and cytological variables with the highest specificity for MDS (h-score). The information from chromosomal abnormalities and somatic mutation patterns was then integrated into a cyto-histological/genetic score (hg-score). This score was able to segregate two groups of h-MDS with a significantly different risk of blast progression ( P  < 0.001). The integration of cyto-histological and genetic features in adult patients with hypocellular BM facilitated segregation into two distinct groups, one with clinical and genetic features highly consistent with myeloid neoplasm, and one with features more consistent with non-malignant BMF.