Large Cell Transformation in Mycosis Fungoides & Sezary Syndrome: An Analysis of 445 Cases
Authors: Lohray Rishabh , Feng Lei , Huen Auris O , Ogundipe Iyanuoluwa , Malpica Luis , Dabaja Bouthaina S. , Dai Julia , Gunther Jillian R. , Hosing Chitra , Miranda Roberto N. , Medeiros L. Jeffrey , Srour Samer A. , Ramdial Jeremy , Vega Francisco , Noorani Mansoor , Ayers Amy A. , Fang Penny Q. , Fayad Luis E. , Pinnix Chelsea C. , Duvic Madeleine , Xu Jie , Flowers Christopher R. , Wu Susan Y. , Kim Kunhwa , Torres-Cabala Carlos P , Iyer Swaminathan P , Nair Ranjit 
Published: December 2024

Introduction:Large cell transformation (LCT) of mycosis fungoides/Sezary syndrome (MF/SS) is associated with an aggressive clinical course and poor overall survival (OS).

Patients and methods: We retrospectively analyzed 2861 MF/SS patients from our institutional lymphoma outcomes database between 1982 through 2023 and identified 445 patients with LCT. OS was defined as survival from time of LCT diagnosis (index LCT) to time of death or last follow up. Kaplan-Meir analysis was done to assess OS.

Results: There were 269 (60.5%) males and 176 (39.5%) females. At the time of index LCT, 384 (86.3%) patients had skin only LCT whereas 61 patients had extracutaneous (13.7%) (nodal or visceral) involvement with or without skin involvement.

The median age at LCT diagnosis was 63 years (range:18-91years). One hundred and sixty-nine (37.5%) patients were diagnosed with LCT at the time of initial diagnosis of MF/SS. The median time to transformation in the remaining patients was 3.14 years (range: 0.10-41.84 years). At the time of index LCT, 193 (43.4%) patients had stages I-IIA (early-stage) and 252 (56.6%) had stages IIB-IVB (advanced-stage).

The OS in advanced-stage MF/SS patients was 32.6 months vs 134.8 months for early-stage patients (p&lt;0.01). Patients with tumors at index LCT had worse OS (32.8 months) vs those with patches (53.7 months) or plaques (56.9 months) (p&lt;0.01). Additionally, among 292 patients tested for serum lactate dehydrogenase (LDH) at the time of LCT diagnosis, patients with an elevated serum LDH had an OS of 14.5 months vs 37.1 months for patients with a normal serum LDH (p&lt;0.01). Patients with age&gt;60 years at time of index LCT had a median OS of 26.1 months whereas patients under 60 years had a median OS of 45.9 months (p&lt;0.01). Finally, patients with a diagnosis of SS prior to LCT diagnosis had the poorest OS (10.5 months) when compared to OS for all variants of MF (OS ranged from 20.45 months to 112.45 months depending on the variant) (p&lt;0.01). One-year, three-year, and five-year OS rates from time of index LCT were 77%, 50%, and 38%, respectively, for patients with MF/SS. Race and sex were not significantly associated with differences in OS. Extracutaneous involvement at index LCT was associated with a difference in OS (28.32 months in those with extracutaneous involvement vs 37.19 months in those without), however the results did not meet significance (p=0.0597). Detailed pathologic, genomic, and treatment response data will also be presented at the time of conference.

Conclusions: Age&gt;60 years, elevated serum LDH levels, tumor morphology on skin, a diagnosis of SS prior to LCT, and advanced-stage disease at time of LCT were associated with worse OS in patients with transformed MF/SS. This study represents the largest group of transformed MF/SS patients ever analyzed from a single institution.