Cutaneous T-cell lymphoma – combination modalities in treatment •Vašků V. • •Ist Dept. of Dermatology and Venereology, • Medical Faculty Masaryk University and St. Ann´s Faculty Hospital, Brno, Czech Republic • • • Cutaneous T-cell lymphoma (CTCL) •Larger spectrum of diseases with two characteristic features: Ø1. Malignant expansion of T- cells clones stopped on the way from bone marrow precursor cells to helper cells Ø2. Forming and location of lymphoma in the skin • CTCL1: EORTC2 Classification •Indolent –Mycosis fungoides (MF) –Mycosis fungoides plus follicular mucinosis –Pagetoid reticulosis –Large-cell CTCL, CD30+ –Lymphomatoid papulosis •Aggressive –Sézary syndrome (SS) –Large-cell CTCL, CD30- –Immunoblastic T-cell lymphoma –Pleomorphic T-cell lymphoma •Provisional –Granulomatous slack skin –CTCL, pleomorphic small/medium-sized T-cell lymphoma –Subcutaneous panniculitis-like T-cell lymphoma 1 CTCL Cuteanous T-Cell Lymphoma, 2 EORTC European Organisation for Research and Treatment of Cancer Cutaneous T-cell lymphoma •Three stages of CTCL with epidermotrophism: ØI. Eczematoid stage (premycotic, patch stage) ØII. Infiltrative stage (plaque stage) ØIII. Tumor stage •The disease usually proceeds from stage to stage, various alterations of more stages can be present simultaneously as well. CTCL: Stage and Prognosis • IA IB IIA IIB III IVA IVB •5-year DSS (%) * 100 96 68 80 40 0 •10-year DSS (%) 98 83 68 42 20 0 •Median survival (yr) >32 12.1 10.0 2.9 3.6-4.6 1.1 1.1 •ODP (%)  9 20 34 •5-year RFS** (%) 50 36 9 •10-year RFS (%) 31 3 1 DSS, disease-specific survival; 2 ODP, overall disease progression; 3 RFS, relapse-free survival Methods used for CTCL treatment in the Ist Dept. of Derm. in Brno •Topically: steroids • tar •Phototherapy: UVB 311 nm • SUP • CUP • PUVA •Photodynamic therapy •Systemic treatment: acitretin • Interferon a2a • Interferon a2b • (steroids) • bexarotene •Radiotherapy in co-operation with Dept. of Oncology Our experience with combination of therapeutical modalities for advanced CTCL •PUVA / UVB 311nm + retinoids •PUVA + interferons •PUVA + retinoids + interferons •PUVA + retionoids + interferons + radiotherapy •PUVA + bexarotene •Other combinations Bexarotene Properties •Novel retinoid rexinoid •Selective retinoid X receptor (RXR) antagonist •Modulates expression of genes regulated by retinoid response elements •Available as topical or systemic treatment •Mono- or combination therapy bexarotene Bexarotene: Adverse Events • Incidence by initial dose (mg/m2/day) •Adverse event 300 (n=84) > 300 (n=53) •Hyperlididaemia 79% 79% •Hypercholestolaemia 32% 62% •Headache 30% 42% •Hypothyroidism 29% 53% •Pruritus 25% 15% •Asthaenia 20% 45% •Leukopenia 17% 47% •Rash 17% 23% •Infection 13% 23% •Exfoliative dermatitis 10% 28% •Diarrhoea 7% 42% •Anaemia 6% 25% •Anorexia 2% 23% Nový obrázek 2 Nik_00026 A:\kozni 5.gif MF, after six month of PUVA Nik_00019 MF, lichenoid form, 1999 A:\kozni 41.gif Nik_00021 MF, lichenoid form, after eight month of PUVA, cumulative dose 86 J/cm2, remission until now A:\kozni 28.gif Sézary syndrome 1998 Nik_00031 A:\kozni 25.gif A:\kozni 29.gif Sézary syndrome, after rePUVA 1054 J/cm2 Nik_00037 MF 1994 Nik_00042 Nik_00064 Nik_00043 In remission after IFNα + acitretin until 2009 I~000040 LyP Immunophenotyping CD 30+ lyp-jedl-1725-05-40x-cd30 J. Feit: www.atlases.muni.cz Dr Remission after rePUVA treatment A:\kozni 3.gif MF 1998 A:\kozni 4.gif MF after 12 month of PUVA and Intron-A cumulative dose 210 J/cm2, in remission with low dose of acitretin until now A:\kozni38.gif MF 1995 A:\kozni 40.gif A:\kozni 37.gif MF 1998, after rePUVA, cumulative dose 500 J/cm2 Nik_00044 Nik_00032 kozni 11 MF - before therapy kozni 9 Nik_0009 M Nik_0015 Remission after IFNα + acitretin Nik_0017 003_19 MF - before therapy, 2007 004_19 002_19 Nový obrázek 12 Nový obrázek 2 011_30 Complete remission after rePUVA + IFNα until now Nový obrázek 9 Nový obrázek 10 MF – before therapy, 2007 nik11641.JPG nik11640.JPG nik11644.JPG nik11643.JPG nik19639.JPG nik19645.JPG nik24066 After 2 years of bexarotene therapy • nik24068 nik23958 MF – before therapy nik25747 MF – after 2 months bexarotene therapy Štrbo L Erythrodermic MF – before therapy 2003 • 0093 039 2006 – after IFNα + acitretin + TSEB nik26335 2009 – bexarotene therapy MF – before therapy Nový obrázek 5 MF – before therapy Nový obrázek 6 3 months bexarotene therapy + PUVA Nový obrázek 3 Nový obrázek 4 Sézary syndrome Nový obrázek 8 Sézary syndrome – 3 months bexarotene + PUVA therapy Nový obrázek 13 •MF before PDT nik00030 •After PDT nik27224 Conclusion •In dermatology we have possibilities to treat CTCL by many methods according to diagnose and staging. •In initial stage of mycosis fungoides we are able to stop or to control it’s development •In Sézary syndrome recent immunotherapy can attribute to longer remission Nik_00074