Project description:BackgroundCutaneous T-cell lymphomas (CTCL) are rare types of non-Hodgkin lymphoma, which present in skin. Mycosis fungoides (MF) and Sézary syndrome (SS) are subtypes which make up two-thirds of all CTCL cases. The phase 3 MAVORIC study (NCT01728805) compared mogamulizumab to vorinostat in MF and SS patients, with post hoc data showing a trend for higher efficacy in mogamulizumab-treated patients as baseline blood tumour burden increases.ObjectivesThe aim of this study was to use updated post hoc analyses in order to examine the efficacy of mogamulizumab and vorinostat in MF patients when stratified by baseline blood involvement and to determine what factors affect time-to-global and time-to-skin response to inform clinical follow-up.MethodsPost hoc analyses were carried out using data from MAVORIC. Overall response rate (ORR), progression-free survival (PFS) and time-to-next-treatment (TTNT) data were used to assess efficacy in patients with MF. Time-to-global response (TTR) was examined by disease subtype, by blood involvement in MF patients, and time-to-skin response was examined by blood involvement in MF patients.ResultsNumerically superior results were seen for ORR, PFS and TTNT in mogamulizumab-treated patients with MF compared with vorinostat, with a trend for outcomes improving with increasing baseline blood class. Statistically significant results for mogamulizumab compared with vorinostat were seen for MF B1 pts for PFS (8.43 vs. 2.83 months, p = 0.003) and TTNT (11.9 vs. 3.13 months, p = 0.002), and for MF B2 pts for ORR (46.2 vs. 9.1 months, p = 0.033).ConclusionsIn mogamulizumab-treated MF patients, ORR and PFS were seen to improve with increasing blood involvement, which led to improved TTNT. TTR was more predictable for mogamulizumab-treated MF patients with blood involvement, and skin response may take longer than previously reported in some patients.
Project description:RationaleMycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. It appears as patches, plaques, and tumors depending on the stage of the disease, which presents a chronic progressive course. Compared to CD4/CD8 MF, CD4/CD8 dual-positive MF is an uncommon immune phenotype.Patient concernsA 36-year-old male patient presented with dryness and scales on his whole body.DiagnosisThe patient was diagnosed with MF based on results of pathological examination, immunohistochemical staining, and T-cell receptor gene rearrangement test.InterventionsThe patient was advised to take an herbal medicine orally twice daily and apply a topical moisturizer after showering.OutcomesAfter treatment and follow-up, the patient's symptoms of dryness and scales improved and his condition stabilized.ConclusionsWhile reviewing the literature, we found no previous reports on the treatment of dual-positive MF with Chinese medicine. In this report, we presented the first case of dual-positive MF successfully treated with Chinese medicine. The results suggest that oral ingestion of herbal medicine may be a feasible method for alleviating clinical symptoms of early stage MF. Therefore, the therapy should be explored for clinical use in the future.
Project description:Mycosis fungoides (MF) is the most common and best studied of cutaneous T-cell lymphoma (CTCL). Three clinical cutaneous stages have been described (patch, plaque and tumor) as the disease progress developing also the disease lymph node, peripheral blood or systemic involvement in late stages. Clinical and pathologic diagnosis of early MF stages (patch and plaque) is difficult as its morphologic similarity to inflammatory dermatoses and low proportion of tumoral cells.
Project description:Mycosis fungoides (MF) is a cutaneous T-cell lymphoma (CTCL) characterized by neoplastic skin-homing T cells. To better understand the immunopathogenesis of MF, we analyzed the functional ability of peripheral blood mononuclear cells (PBMC) from early and late MF/CTCL patients to express cytokine genes. In late stage MF/CTCL, patients were separated into those with blood involvement (+B) and without blood involvement (-B).We analyzed T(H)1 (interleukin 2 (IL-2), IFN-gamma), T(H)2 (IL-4, IL-5, IL-10, IL-13), and T(H)17 (IL-17) cytokine gene expression from activated PBMCs from normal (n = 12), psoriasis (n = 6), early MF/CTCL (n = 11), and late MF/CTCL+B (n = 4) and MF/CTCL-B (n = 3) by quantitative real-time PCR.PBMCs from early MF/CTCL and psoriasis showed higher induction of IL-2, IL-4, and IFN-gamma genes than those from normal and late MF/CTCL-B and MF/CTCL+B (P < 0.05) in descending order. PBMCs from late MF/CTCL-B exhibited generally the highest level of IL-5, IL-10, IL-13, and IL-17 expression compared with the other groups. PBMCs from early MF/CTCL and late MF/CTCL-B had similarly elevated IL-13 and IL-17. Of all groups, PBMCs from late MF/CTCL+B had the lowest levels of IL-2 (P < 0.05), IL-4, IFN-gamma, IL-13, and IL-17.The different pattern of cytokine gene expression suggests a change in immune function in MF/CTCL from early MF/CTCL to late MF/CTCL-B to late MF/CTCL+B. These stages are consistent with localized disease associated with an anti-tumor immune response and late MF/CTCL associated with a loss of immune function mediated by malignant T cells that share regulatory T cell-like properties.
Project description:BackgroundAccurate Sezary cell detection in peripheral blood of mycosis fungoides/Sezary syndrome (MF/SS) patients by flow cytometry can be difficult due to overlapping immunophenotypes with normal T cells using standard markers. We assessed the utility of programmed death-1 (PD-1/CD279), a transmembrane protein expressed in some hematopoietic cells, for identification and quantitation of circulating Sezary cells among established markers using flow cytometry.Methods50 MF/SS and 20 control blood samples were immunophenotyped by flow cytometry. Principal component analysis (PCA) assessed contributions of antigens to separation of abnormal from normal T cell populations. PD-1 was assessed over time in blood and bone marrow of available MF/SS cases.ResultsNormal CD4+ T cells showed dim/intermediate to absent PD-1 expression. PD-1 in Sezary cells was informatively brighter (≥1/3 log) than internal normal CD4+ T cells in 39/50 (78%) cases. By PCA, PD-1 ranked 3rd behind CD7 and CD26 in population separation as a whole; it ranked in the top 3 markers in 32/50 (64%) cases and 1st in 4/50 (8%) cases when individual abnormal populations were compared to total normal CD4+ T cells. PD-1 clearly separated Sezary from normal CD4+ T cells in 15/26 (58%, 30% of total) cases with few and subtle alterations of pan-T cell antigens/CD26 and was critical in 6 (12% of total), without which identification and quantification were significantly affected or nearly impossible. PD-1 remained informative in blood/bone marrow over time in most patients.ConclusionsPD-1 significantly contributes to accurate flow cytometric Sezary cell assessment in a routine Sezary panel.
Project description:BackgroundMycosis fungoides (MF) is the most common cutaneous T-cell lymphoma, for which there is no cure. Immune checkpoint inhibitors have been tried in MF but the results have been inconsistent. To gain insight into the immunogenicity of MF we characterized the neoantigen landscape of this lymphoma, focusing on the known predictors of responses to immunotherapy: the quantity, HLA-binding strength and subclonality of neoantigens.MethodsWhole exome and whole transcriptome sequences were obtained from 24 MF samples (16 plaques, 8 tumors) from 13 patients. Bioinformatic pipelines (Mutect2, OptiType, MuPeXi) were used for mutation calling, HLA typing, and neoantigen prediction. PhyloWGS was used to subdivide malignant cells into stem and clades, to which neoantigens were matched to determine their clonality.ResultsMF has a high mutational load (median 3,217 non synonymous mutations), resulting in a significant number of total neoantigens (median 1,309 per sample) and high-affinity neoantigens (median 328). In stage I disease most neoantigens were clonal but with stage progression, 75% of lesions had >50% subclonal antigens and 53% lesions had CSiN scores <1. There was very little overlap in neoantigens across patients or between different lesions on the same patient, indicating a high degree of heterogeneity.ConclusionsThe neoantigen landscape of MF is characterized by high neoantigen load and significant subclonality which could indicate potential challenges for immunotherapy in patients with advanced-stage disease.
Project description:Cutaneous T-cell lymphomas are a heterogeneous collection of non-Hodgkin lymphomas that arise from skin-tropic memory T lymphocytes. Among them, mycosis fungoides (MF) and Sézary syndrome (SS) are the most common malignancies. Diagnosis requires the combination of clinical, pathologic, and molecular features. Significant advances have been made in understanding the genetic and epigenetic aberrations in SS and to some extent in MF. Several prognostic factors have been identified. The goal of treatment is to minimize morbidity and limit disease progression. However, hematopoietic stem cell transplantation, considered for patients with advanced stages, is the only therapy with curative intent.