Real-World Analysis of Mycosis Fungoides and Sezary Syndrome in a Lower Middle-Income Country: A 25-Year Retrospective Cohort Study
Authors: Floyd Aristizábal Danielle , Arias Oriana , Arrieta Elizabeth , Silva Nhora , Rincon Andres Camilo , Betancourth Luisa Maria , Hidalgo Alejandra , Lasso Andrea , Valcarcel Bryan , Proaño Catalina , Malpica Castillo Luis Enrique 
Published: December 2024

Introduction

Mycosis fungoides (MF) and Sezary syndrome (SS) are rare forms of non-Hodgkin lymphoma, representing about 4% of cases and primarily affecting the skin, with an incidence of 6 cases per million annually in the US. These forms of cutaneous T-cell lymphoma (CTCL) are difficult to diagnose due to their similarity to other chronic skin conditions. Histopathology is crucial but often requires additional clinical, immunopathological, and genomic sequencing for a definitive diagnosis. In Latin America, the incidence of MF/SS is poorly documented due to the lack of centralized cancer registries and underreporting. This study aims to describe the clinical presentation, treatment patterns, and outcomes of MF/SS in a single referral center in Colombia, providing insights into managing these diseases in an underserved area.

Methods

A retrospective cohort study was conducted on patients (pts) with a pathological diagnosis of MF/SS. Data were collected between 1998-2023. The stage of the disease was established based on the TNM classification according to the MF Cooperative Group (MFCG) criteria. Overall survival (OS) was estimated from diagnosis to death from any cause, while progression-free survival (PFS) was from diagnosis to relapse, progression, or death. Vital status was verified by linking records with the national vital status registry. The Kaplan-Meier method was used to estimate survival probabilities, and the Log-Rank test was used to test group differences.

Results

Seventy-one pts were included. The median age at diagnosis was 60 years (range 14-73), with 3 cases under 17 years and a slight female predominance (61%). Most pts had advanced-stage disease (MFCG stage III-IV, 59%). Forty-five pts (63%) had a granulomatous presentation, 22 (31%) had folliculotropic, and 3 (4.2%) had pagetoid reticulosis. Immunophenotypic markers were not available for all pts, but the most frequently observed markers were, in order: CD3, CD2, CD8, CD7, CD30, and CD25. PDL-1 was detected in 2 pts, HTLV-1 infection in 2 pts, and Hepatitis C virus infection in 1 pt. The most common first-line treatment was skin-directed therapy (phototherapy, topical corticosteroids, and radiotherapy) in 58 (81.6%) pts. Phototherapy with UVB was given to 42 pts, of whom 18 reported interrupted therapy due to disease progression (n=11), lost to follow-up (n=5), and skin-related complications requiring hospitalization (n=2). First-line single-agent and multi-agent chemotherapy was given to 6 (8.4%) and 5 (7%) pts, respectively; only 1 received extracorporeal photopheresis (ECP).

With a median follow-up of 32 months, the 3-year OS rates were 80% and 44% for pts with early- and advanced-stage, respectively. The median PFS was 1 month. Pts treated with skin-directed therapy had better 2-year PFS than pts treated with chemotherapy (16% vs 2%, p=0.001), likely due to a more indolent disease course.

Conclusions

This study presents one of the largest cohorts of MF/SS in Latin America. The analysis shows a higher frequency of MF/SS in older individuals, although rare cases in the pediatric population were reported. Most pts were women with the granulomatous variant. Skin-directed therapy was the predominant first-line treatment, yet many pts experienced interruptions. OS in this cohort was comparable to international reports. However, a higher incidence of advanced-stage disease was observed compared to prior studies (59% in this cohort vs 20-30% in the US), likely due to delays in diagnosis and limited access to care. Pts who received single-agent or multi-agent chemotherapy had worse outcomes, likely due to the more advanced stage of their disease. Although ECP has shown to improve quality of life in CTCL pts, access is limited in LMIC, with only one patient treated in this cohort. These findings highlight the diagnostic and therapeutic challenges of MF/SS in resource-limited settings, emphasizing the urgent need for improved healthcare infrastructure and early detection programs.