New research shows TP53 multihit alterations in myelodysplastic neoplasms have a less severe impact in patients with isolated del(5q). These patients had significantly better survival and delayed disease progression compared to other subtypes.
Myelodysplastic neoplasms are diverse disorders with prognosis heavily influenced by genetics. TP53 multihit alterations usually indicate poor outcomes, while isolated del(5q) typically carries a favorable prognosis. It was unclear if TP53 multihit alterations in del(5q) patients still conferred the same negative effect.
A retrospective analysis of 43 patients with isolated del(5q) and TP53 multihit alterations compared them to 68 low blast MDS patients with TP53 multihit without del(5q). The del(5q) group had higher platelet counts, more SF3B1 mutations, and were less often high-risk by scoring systems.
Survival outcomes were markedly different. Median overall survival was 70.2 months in the del(5q) group versus 13.9 months in the comparator. Time to acute myeloid leukemia progression was 31.9 months versus 7.2 months.
The survival advantage remained significant even when compared to patients without complex karyotype. Overall survival was 70.2 months versus 39.9 months, and time to AML progression was 31.9 months versus 11.4 months.
These findings suggest isolated del(5q) may mitigate the adverse impact of TP53 multihit alterations, challenging conventional risk understanding and emphasizing the importance of cytogenetic context in risk stratification.