Introduction
Large cell transformation (LCT) in mycosis fungoides/Sézary syndrome (MF/SS) portends poor survival, yet specific risk factors and real-world disparities in outcomes remain incompletely defined.
Objective
In a large retrospective cohort of patients with MF/SS, we evaluated clinicopathologic and social factors linked to LCT; and their impact on overall survival (OS).
Methods
We conducted a multicenter retrospective study of patients with MF/SS diagnosed between 2000-2024. Social Deprivation Index (SDI) assessed socioeconomic status using 2019 zip–code census data. LCT predictors were determined with multivariable logistic regression, and OS was analyzed with Cox models.
Results
LCT was reported in 163 of 979 patients (16.6%). Multivariable logistic modeling of age, SDI, LDH, CD30 positivity, and ISCL stage at diagnosis demonstrated incremental stage was independently associated with LCT risk (OR 1.19, 95% CI 1.07-1.31; p=0.001). Median OS was 138 months (95% CI, 107–not reached; n=935). In multivariable analysis adjusting for age, SDI, stage, and LDH at diagnosis, LCT was independently associated with lower OS (HR 2.97, 95% CI 1.45–6.12; p = 0.003). 82% (32/39) of LCT cases with available staining demonstrated CD30 expression ≥1%. Among 43 patients with treatment data, first-line complete response was 32.6%, partial response 48.8%, progressive disease 14%, and stable disease 4.7%; brentuximab-based regimens predominated (35%) followed by CHOP (18.6%).
Conclusions
In this real-world MF/SS cohort, LCT was a strong adverse factor for OS, and higher ISCL stage at diagnosis correlated with LCT risk. Brentuximab-based regimens were the most common initial therapy at transformation, with frequent post-LCT responses. These findings support risk-adapted surveillance, timely treatment escalation, and prospective evaluation of brentuximab-based therapies in high-risk patients.
