Comprehensive analysis of prognostic factors in myelodysplastic syndromes with isolated deletion of chromosome 5q.

abstractMyelodysplastic syndromes (MDS) with isolated deletion of chromosome 5q [MDS-del(5q)] constitute a distinct biological entity traditionally associated with favorable outcomes, although up to one-quarter of patients progress to acute myeloid leukemia (AML). Existing prognostic models, developed in heterogeneous MDS populations, may not adequately capture risk within this subgroup. We assembled an international cohort of 682 patients with MDS-del(5q) to evaluate the performance of the Revised International Prognostic Scoring System (IPSS-R) and its molecular version (IPSS-M), identify prognostic variables, and develop a disease-specific prognostic tool, the IPSS-del(5q). Most patients were classified as lower risk by IPSS-R (94.4%) and IPSS-M (85.5%), yet both systems showed limited discriminatory ability (concordance indices [C-indices] ≈0.5). Independent adverse prognostic factors included age of ≥70 years, male sex, anemia (hemoglobin ≤10 g/dL), thrombocytopenia (platelet count ≤100 × 109/L), the presence of 1 additional chromosomal abnormality, ≥2 gene mutations, SF3B1 mutations, and high-risk TP53 status. Six variables were included in the IPSS-del(5q), stratifying patients into standard-risk (74.3%) and high-risk (25.7%) groups with significantly different leukemia-free survival (69.2 months vs 32.0 months, respectively; P< .01). Moreover, this model reclassified 19.1% of patients in lower-risk IPSS-R group and 14.6% of those in lower-risk IPSS-M group into the high-risk IPSS-del(5q) group. However, its discriminative power remained modest, with a C-index of 0.60. Overall, to our knowledge, this study provides the most comprehensive prognostic evaluation of MDS-del(5q) to date, demonstrates the limited discriminatory capacity of existing MDS scores in this entity, and underscores the need to develop refined disease-specific prognostic approaches for this MDS subtype.