LY04 Large-cell transformation of mycosis fungoides: analysis of presentation, treatment and outcomes from a UK tertiary centre

Abstract

Large-cell transformation (LCT) occurs in 5–26% of patients with mycosis fungoides (MF) or Sézary syndrome (SS). LCT is defined as lymphoma cells > 4 times the normal size, either forming ≥ 25% of the infiltrate or in clusters. LCT is associated with aggressive clinical course and inferior survival. It was recently included in the NCCN guidelines but is absent from most clinical guidelines. We describe presenting characteristics, treatment strategies and survival outcomes of patients with LCT in MF or SS from a UK tertiary centre. This was a retrospective analysis of patients with clinicopathological diagnosis of MF or SS with LCT from University Hospitals Birmingham. In total, 73 patients were identified for analysis. Their median age was 64 years, 62% were male and 11% had SS. At diagnosis of MF or SS, 30% had early-stage (I–IIA) and 70% had advanced-stage (IIB–IV) disease. The median time to LCT was 6 months; 34% presented with LCT at the initial diagnosis of MF or SS. At LCT diagnosis, 48% had unifocal cutaneous-only disease, 49% multifocal cutaneous-only disease, and 15% extracutaneous involvement. CD30 expression was positive (> 10%) in 70%. First-line treatments were highly varied: radiotherapy (43%), single-agent chemotherapy (28%), interferon (27%), retinoids (10%), multiagent chemotherapy (6%) and monoclonal antibodies (6%). Overall, 10% underwent allogeneic stem cell transplantation and 26% received total-skin electron beam therapy. The median overall survival was 2.7 years (interquartile range 1.2–5.0), with 2-year, 5-year and 10-year overall survival rates of 69%, 34% and 4%, respectively. Disease-specific survival rates were substantially higher (80%, 49% and 16%, respectively), indicating competing mortality risks. Patients with LCT concurrent with a diagnosis of MF or SS showed superior overall survival (4.30 vs. 2.02 years) but worse disease-specific survival (0.92 vs. 1.93 years). Multifocal cutaneous disease demonstrated the worst ­disease-specific survival (1.18 years). CD30 positivity was associated with better survival. LCT demonstrates significant heterogeneity in presentation and outcome. Disease-specific survival analysis revealed important competing risks, particularly in patients with LCT concurrent with MF or SS diagnosis. Treatment strategies remain highly varied, highlighting the need for risk-adapted treatment algorithms.