Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of malignant lymphomas that share the propensity for malignant T lymphocytes expressing cutaneous lymphocyte antigen to infiltrate the skin. Mycosis fungoides (MF) is the most common variant of CTCL, representing approximately 44% of all cases. Sézary syndrome (SS) is a leukemic variant of CTCL, affecting approximately 3% of patients. MF and SS are malignant proliferations of mature memory T lymphocytes of the helper phenotype (CD4+CD45RO+), which render patients immunocompromised even at the earliest stages of the disease. Advanced stages are associated with severe immune suppression. Diagnosis is established by skin biopsy followed by staging workup, which includes radiologic imaging and pathologic evaluation of the lymph nodes, internal organs, blood, and marrow, as appropriate, according to presenting manifestations of the disease.
MF and SS are divided into early and advanced stages for therapeutic and prognostic reasons. In the early stages, the disease follows an indolent course and has a favorable prognosis. In advanced stages, the prognosis is poor. There are numerous therapeutic options, but no treatment has been proven to improve survival. Nonetheless, newer studies suggest that survival of modern cohorts is longer than historically documented cohorts. Multiagent chemotherapy is inferior to immune-modulating and biologic therapies. Considering the overall protracted course of the disease, its indolent character, the immunocompromised status of the patients, and the absence of definitive therapy, multiagent chemotherapy contributing to immunosuppression should be reserved for palliation of end-stage disease or as a bridge to stem cell transplantation, with the goal of definitive cure. There are several single agents approved by the Federal Drug Administration for therapy of patients with CTCL that are safe and effective against the disease and may be used in the therapeutic ladder before multiagent regimens. Novel single agents and combinations of new and older agents are currently in clinical trials. Because no single therapy is considered to be the standard of care for MF or SS, clinical trials remain an important option for most patients. The goal of therapy is to induce long-term remissions without compromising patients’ immunity and improve the patient’s quality of life.
Acronyms and Abbreviations
ALCL, anaplastic large cell lymphoma; ALK-1, anaplastic lymphoma kinase-1; ATRA all-trans retinoic acid; BCNU, bis-chloroethyl-nitrosourea or carmustine; CCR4, CC chemokine receptor 4; CDR, complementarity determining region; CI, confidence interval; CLA, cutaneous lymphocyte antigen; CR, complete remission; CT, computed tomography; CTCL, cutaneous T-cell lymphoma; DD, denileukin diftitox; ECP, extracorporeal photopheresis; EORTC, European Organization for Research and Treatment of Cancer; FDA, Federal Drug Administration; FISH, fluorescent in situ hybridization; FLASH, fluorescent light activated synthetic hypericin; FNAC, fine needle aspiration cytology; GCNA, gene copy number abnormalities; GVHD, graft versus host disease; GVL, graft versus lymphoma; HDACi, histone deacetylase inhibitor; HTLV-1, human T-lymphotropic virus type 1; HTS, high throughput sequencing; IFN, interferon; Ig, immunoglobulin; IL, interleukin; KIR, killer immunoglobulin-like receptor; LEBT, localized electron beam therapy; LPD, lymphoproliferative disorder; LyP, lymphomatoid papulosis; MAC, myeloablative conditioning; MF, mycosis fungoides; ...