75 results on '"Amitay-Laish I"'
Search Results
2. Erythrodermic mycosis fungoides and Sézary syndrome treated with extracorporeal photopheresis as part of a multimodality regimen: A single-centre experience
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Atzmony, L., Amitay-Laish, I., Gurion, R., Shahal-Zimra, Y., and Hodak, E.
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- 2015
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3. Paediatric mycosis fungoides – characteristics, management and outcomes with particular focus on the folliculotropic variant.
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Reiter, O., Amitay‐Laish, I., Oren‐Shabtai, M., Feinmesser, M., Ben‐Amitai, D., and Hodak, E.
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MYCOSIS fungoides , *PEDIATRICS , *DISEASE progression , *SYMPTOMS , *PHOTOCHEMOTHERAPY - Abstract
Background: The literature on paediatric mycosis fungoides (MF) and especially its folliculotropic variant (FMF) is sparse. Objectives: To describe the clinical manifestations, treatments, outcomes and long‐term course of paediatric MF, including FMF. Methods: A retrospective analysis was conducted of all consecutive MF patients diagnosed at ≤18 years attending two medical centres in 1995–2015. Results: The cohort included 71 patients, all but two of whom had early‐stage disease: hypopigmented (55%), folliculotropic (42%) and classical MF (39%), alone or in combination. The head and neck area were involved in 43% of patients with early‐stage FMF compared to 12% of the non‐FMF group (P = 0.004). There was no difference in the involvement of other body areas between the groups. Pruritus, although mild, was more often recorded among patients with early‐stage FMF compared to non‐FMF (58% vs. 29%, respectively, P = 0.02). Complete response (CR) was achieved in 60 of the 69 patients with early‐stage MF (87%) after an average of 1.8 treatment modalities. NBUVB was the most administered treatment to non‐FMF patients with CR rates of 63% vs. 29% of FMF patients (P = 0.04). Systemic/bath PUVA and UVA+NBUVB were the most administered treatments to FMF patients with CR rates of 60% vs. 81% for non‐FMF patients (P = 0.17). During a mean follow‐up of 9.2 years (range 1–24), stage progression was observed in four (6%) of the patients with early‐stage disease, two of whom (all FMF) to advanced stage. Conclusions: Paediatric MF presents as an early‐stage disease with over‐representation of hypopigmented and FMF variants. NBUVB and UVA‐based therapies yield good response rates in non‐FMF and FMF patients, respectively. Disease course is indolent, and even on relatively long follow‐up, it has a very low progression rate from early to advanced‐stage disease, occurring in patients with FMF. We propose a treatment algorithm for paediatric MF. [ABSTRACT FROM AUTHOR]
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- 2022
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4. Juvenile onset of primary low-grade cutaneous B-cell lymphoma
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Amitay-Laish, I., Feinmesser, M., Ben-Amitai, D., David, M., Manor, Y., Kidron, D., Barzilai, A., and Hodak, E.
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- 2009
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5. Mycosis fungoides‐derived exosomes promote cell motility and are enriched with microRNA‐155 and microRNA‐1246, and their plasma‐cell‐free expression may serve as a potential biomarker for disease burden.
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Moyal, L., Arkin, C., Gorovitz‐Haris, B., Querfeld, C., Rosen, S., Knaneh, J., Amitay‐Laish, I., Prag‐Naveh, H., Jacob‐Hirsch, J., and Hodak, E.
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MYCOSIS fungoides ,CELL motility ,EXOSOMES ,CUTANEOUS T-cell lymphoma ,BIOMARKERS ,MYCOSES - Abstract
Summary: Background: Literature regarding exosomes as mediators in intercellular communication to promote progression in mycosis fungoides (MF) is lacking. Objectives: To characterize MF‐derived exosomes and their involvement in the disease. Methods: Exosomes were isolated by ultracentrifugation from cutaneous T‐cell lymphoma (CTCL) cell lines, and from plasma of patients with MF and controls (healthy individuals). Exosomes were confirmed by electron microscopy, NanoSight and CD81 staining. Cell‐line exosomes were profiled for microRNA array. Exosomal microRNA (exomiRNA) expression and uptake, and plasma‐cell‐free microRNA (cfmiRNA) were analysed by reverse‐transcriptase quantitative polymerase chain reaction. Exosome uptake was monitored by fluorescent labelling and CD81 immunostaining. Migration was analysed by transwell migration assay. Results: MyLa‐ and MJ‐derived exosomes had a distinctive microRNA signature with abundant microRNA (miR)‐155 and miR‐1246. Both microRNAs were delivered into target cells, but only exomiR‐155 was tested, demonstrating a migratory effect on target cells. Plasma levels of cfmiR‐1246 were significantly highest in combined plaque/tumour MF, followed by patch MF, and were lowest in controls (plaque/tumour > patch > healthy), while cfmiR‐155 was upregulated only in plaque/tumour MF vs. controls. Specifically, exomiR‐1246 (and not exomiR‐155) was higher in plasma of plaque/tumour MF than in healthy controls. Plasma exosomes from MF but not from controls increased cell migration. Conclusions: Our findings show that MF‐derived exosomes promote cell motility and are enriched with miR‐155, a well‐known microRNA in MF, and miR‐1246, not previously reported in MF. Based on their plasma expression we suggest that they may serve as potential biomarkers for tumour burden. What is already known about this topic? Cancer‐derived exosomes mediate tumour progression by delivering microRNAs such as miR‐155 and miR‐1246 into recipient cells, and their cell‐free (cf) components are upregulated in plasma of patients with cancer. What does this study add? Mycosis fungoides (MF) cell‐line exosomes carry miR‐155 and miR‐1246, deliver them to recipient cells (malignant and benign), and increase their migration through miR‐155.cfmiR‐1246, cfmiR‐155 and exosomal miR‐1246 are upregulated in plasma of patients with MF, mainly in tumour/plaque‐stage disease. What is the translational message? Extracellular miR‐155 and miR‐1246 may serve as targets for novel treatments and as promising noninvasive biomarkers for tumour burden in MF. Linked Comment: I. Pospischil and E. Guenova. Br J Dermatol 2021; 185:884–886. [ABSTRACT FROM AUTHOR]
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- 2021
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6. Unilesional mycosis fungoides is associated with increased expression of microRNA‐17~92 and T helper 1 skewing.
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Moyal, L., Gorovitz‐Haris, B., Yehezkel, S., Jacob‐Hirsch, J., Bershtein, V., Barzilai, A., Rotem, C., Sherman, S., Amitay‐Laish, I., Feinmesser, M., and Hodak, E.
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MYCOSIS fungoides ,PTEN protein ,TH2 cells ,BIOMARKERS ,TH1 cells ,POLYMERASE chain reaction ,INTERLEUKIN-22 ,INTERLEUKIN-9 - Abstract
Summary: Background: The molecular basis of unilesional mycosis fungoides (MF), characterized by a solitary lesion that is clinicopathologically indistinguishable from multifocal patch or plaque MF (early MF), is unknown. Objectives: To investigate the microRNA profile in unilesional MF distinguishing it from early MF. Methods: Biopsy samples of unilesional MF and early MF were evaluated with the Affymetrix microRNA array, with further comparison with inflammatory dermatosis, using quantitative polymerase chain reaction. NanoString technology was applied to analyse the gene expression of T helper (Th)1 immune markers, and immunohistochemistry was used to evaluate CXCR3 and GATA‐binding protein 3 (GATA3) markers for Th1 and Th2 cells, respectively. Results: Unilesional MF had a significantly higher level of expression of all members of the microRNA miR‐17~92 cluster than early MF. Specifically, unilesional MF had a higher miR‐17 level than early MF and inflammatory dermatoses. There was downregulation of the expression of phosphatase and tensin homolog (PTEN) and CREB1, known targets of miR‐17~92 members; higher gene expression of interleukin‐2 and interferon‐γ; and a statistically lower average percentage of GATA3+ dermal cells (6·7% vs. 42·3%), were detected in unilesional MF compared with early MF. High immunoreactivity of CXCR3 was noted in both unilesional and early MF. Conclusions: Unilesional MF exhibits a microRNA profile distinct from that of conventional early MF, with a higher level of miR‐17~92 members along with Th1 skewing. These findings suggest a robust reactive T‐cell immune response in unilesional MF and might account for the localized nature of this disease. What's already known about this topic? Unilesional mycosis fungoides (MF) is characterized by a solitary lesion that is clinicopathologically indistinguishable from multifocal early MF.The molecular basis and the cytokine profile of unilesional MF are unknown. What does this study add? Compared with early MF lesions, unilesional MF is typified by high expression of the microRNA miR‐17˜92 cluster, high T helper (Th)1 cytokine profile and low Th2 dermal lymphocytes. What is the translational message? Whether induction of miR‐17˜92 might serve as a target for treatment of MF to promote anticancer response needs further studies. Linked Comment: Querfeld. Br J Dermatol 2019; 180:984–985. Respond to this article [ABSTRACT FROM AUTHOR]
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- 2019
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7. Corrections to “Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium”
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Quaglino, P., Maule, M., Prince, H.M., Porcu, P., Horwitz, S., Duvic, M., Talpur, R., Vermeer, M., Bagot, M., Guitart, J., Papadavid, E., Sanches, J.A., Hodak, E., Sugaya, M., Berti, E., Ortiz-Romero, P., Pimpinelli, N., Servitje, O., Pileri, A., Zinzani, P.L., Estrach, T., Knobler, R., Stadler, R., Fierro, M.T., Alberti Violetti, S., Amitay-Laish, I., Antoniou, C., Astrua, C., Chaganti, S., Child, F., Combalia, A., Fabbro, S., Fava, P., Grandi, V., Jonak, C., Martinez-Escala, E., Kheterpal, M., Kim, E.J., McCormack, C., Miyagaki, T., Miyashiro, D., Morris, S., Muniesa, C., Nikolaou, V., Ognibene, G., Onida, F., Osella-Abate, S., Porkert, S., Postigo-Llorente, C., Ram-Wolff, C., Ribero, S., Rogers, K., Sanlorenzo, M., Stranzenbach, R., Spaccarelli, N., Stevens, A., Zugna, D., Rook, A.H., Geskin, L.J., Willemze, R., Whittaker, S., Hoppe, R., Scarisbrick, J., and Kim, Y.
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- 2019
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8. Paediatric primary cutaneous marginal zone B-cell lymphoma: does it differ from its adult counterpart?
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Amitay ‐ Laish, I., Tavallaee, M., Kim, J., Hoppe, R.T., Million, L., Feinmesser, M., Fenig, E., Wolfe, M.E.L., Hodak, E., and Kim, Y.H.
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B cell lymphoma , *LYMPHOMAS , *TISSUE wounds , *WOUNDS & injuries , *MEDICAL records - Abstract
Background Primary cutaneous marginal zone B-cell lymphoma ( PCMZL) has rarely been reported in patients younger than 20 years. Objectives To report our experience with PCMZL in the paediatric/adolescent age group. Methods Medical records of patients diagnosed with PCMZL before age 20 years and managed at two cutaneous lymphoma clinics in the U.S.A. and Israel from 1992 to 2015 were reviewed. Results The study group included 11 patients (six girls; median age 16 years, range 6-19·5); 10 had generalized/multifocal (T3) and one had regional/localized (T2) disease. Lesions were located on the limbs in all patients and the trunk in six; two had facial lesions. Staging in all but one was based on whole-body computed tomography or positron emission tomography. Initial management in most patients included nonradiation modalities: one patient with localized disease received intralesional steroids; six patients with multifocal disease received the following: topical/intralesional steroids ( n = 3); excision ( n = 2); 'watch and wait' ( n = 1). No extracutaneous progression was noted during a median follow-up of 5·5 years (mean 7·5, range 0·5-14). At present, five patients are in complete remission. Conclusions Based on our data (largest series in the literature with the longest follow-up), the clinicopathological presentation and course of PCMZL in the paediatric/adolescent age group are similar to those in adults. Given the indolent course and the long life expectancy of these young patients, the cumulative risk of imaging studies and the age-related potential toxicity of treatment, especially radiation, should be taken into consideration. [ABSTRACT FROM AUTHOR]
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- 2017
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9. Unilesional folliculotropic mycosis fungoides: a unique variant of cutaneous lymphoma.
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Amitay ‐ Laish, I., Feinmesser, M., Ben ‐ Amitai, D., Fenig, E., Sorin, D., and Hodak, E.
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MYCOSIS fungoides , *ACQUISITION of data , *ELECTRON beams , *CLINICAL trials , *LYMPHOCYTES , *THERAPEUTICS - Abstract
Background: Unilesional folliculotropic mycosis fungoides (UFMF) has been rarely reported. Objective: The aim of this study was to describe our experience with UFMF. Methods: Data were collected on all patients with clinicopathological UFMF who attended the Department of Dermatology of a tertiary university-affiliated medical centre in 1996-2013 and were followed prospectively. Results: The sample included seven patients (five male, two female) of mean age 38 years at diagnosis; two were aged <18 years. The lesion presented as a solitary patch/plaque with follicular accentuation in five patients, an infiltrated plaque devoid of hair in one and with follicular nodules in one. Four patients had alopecia, and one, secondary anetoderma. The lesion was located on a limb in four patients, the trunk in two, and the face in one. In all cases, the atypical folliculotropic lymphocytes expressed mainly surface CD4+. Monoclonality was detected in three of the six patients analysed. Treatment consisted of localized electron beam in five patients, all of whom had a complete response (CR), and excision in one patient. The remaining patient, a 9-year-old boy, was treated with topical psoralen and UVA with CR. The duration of follow-up was 0.5-10 years (mean 4). There were no recurrences in six patients and local recurrence in one. Conclusion: UFMF presents at a young age, usually with early disease clinical morphology. The treatment goal should be cure. Our experience indicates an excellent prognosis of early UFMF with no multifocal/internal spread. [ABSTRACT FROM AUTHOR]
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- 2016
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10. Ther-O-08 - Broad-band ultraviolet A combined with narrow-band ultraviolet B: an effective modality for early folliculotropic mycosis fungoides and early mycosis fungoides refractory to narrow-band ultraviolet B.
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Amitay-Laish, I, Naveh, H Prag, Holzman, R, Baker, A Abo, Raviv, A, Didkovsky, E, and Hodak, E
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THERAPEUTIC use of ultraviolet radiation , *MEDICAL radiology , *MYCOSIS fungoides , *CONFERENCES & conventions , *TREATMENT effectiveness , *ULTRAVIOLET radiation - Published
- 2022
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11. Hyperpigmented mycosis fungoides: An unusual variant of cutaneous T-cell lymphoma with a frequent CD8+ phenotype.
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Pavlovsky L, Mimouni D, Amitay-Laish I, Feinmesser M, David M, and Hodak E
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- 2012
12. A-152 Dissecting the role of CXCR4 in mycosis fungoides: from gene editing to therapeutic molecule.
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Moyal, L., Da'adoosh, B., Gorovitz, B., Mironovich, A., Omar, R., Khoury, H., Tsvetkova, M., Aronovich, A., Amitay-Laish, I., Naveh, H. Prag, Buzhansky, L., Shankar, S., Binyamini, R., and Hodak, E.
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MYCOSIS fungoides , *CONFERENCES & conventions , *SMALL molecules , *GENOME editing , *CHEMOKINE receptors - Published
- 2024
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13. Crosslinking of Ly6a metabolically reprograms CD8 T cells for cancer immunotherapy.
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Maliah A, Santana-Magal N, Parikh S, Gordon S, Reshef K, Sade Y, Khateeb A, Richter A, Gutwillig A, Parikh R, Golan T, Krissi M, Na M, Binshtok G, Manich P, Elkoshi N, Grisaru-Tal S, Zemser-Werner V, Brenner R, Vaknine H, Nizri E, Moyal L, Amitay-Laish I, Rosemberg L, Munitz A, Kronfeld-Schor N, Shifrut E, Kobiler O, Madi A, Geiger T, Carmi Y, and Levy C
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- Animals, Mice, Mice, Inbred C57BL, Cell Line, Tumor, Humans, Melanoma, Experimental immunology, Melanoma, Experimental therapy, Melanoma, Experimental pathology, Female, Programmed Cell Death 1 Receptor metabolism, Programmed Cell Death 1 Receptor antagonists & inhibitors, Programmed Cell Death 1 Receptor immunology, Skin Neoplasms immunology, Skin Neoplasms therapy, Skin Neoplasms pathology, Mitochondria metabolism, Melanoma immunology, Melanoma therapy, Interferon Type I metabolism, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, Antigens, Ly metabolism, Antigens, Ly immunology, Immunotherapy methods, Tumor Microenvironment immunology
- Abstract
T cell inhibitory mechanisms prevent autoimmune reactions, while cancer immunotherapy aims to remove these inhibitory signals. Chronic ultraviolet (UV) exposure attenuates autoimmunity through promotion of poorly understood immune-suppressive mechanisms. Here we show that mice with subcutaneous melanoma are not responsive to anti-PD1 immunotherapy following chronic UV irradiation, given prior to tumor injection, due to the suppression of T cell killing ability in skin-draining lymph nodes. Using mass cytometry and single-cell RNA-sequencing analyzes, we discover that skin-specific, UV-induced suppression of T-cells killing activity is mediated by upregulation of a Ly6a
high T-cell subpopulation. Independently of the UV effect, Ly6ahigh T cells are induced by chronic type-1 interferon in the tumor microenvironment. Treatment with an anti-Ly6a antibody enhances the anti-tumoral cytotoxic activity of T cells and reprograms their mitochondrial metabolism via the Erk/cMyc axis. Treatment with an anti-Ly6a antibody inhibits tumor growth in mice resistant to anti-PD1 therapy. Applying our findings in humans could lead to an immunotherapy treatment for patients with resistance to existing treatments., (© 2024. The Author(s).)- Published
- 2024
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14. Real-world study of pegylated interferon α-2a to treat mycosis fungoides/Sézary syndrome using time to next treatment as a measure of clinical benefit: an EORTC CLTG study.
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Mitsunaga K, Bagot M, Ram-Wolff C, Guenova E, von Gugelberg C, Hodak E, Amitay-Laish I, Papadavid E, Jonak C, Porkert S, Scarisbrick J, Applewaite R, Beylot-Barry M, Nicolay J, Quaglino P, Sanches JA, Cury-Martins J, Lora-Pablos D, and Ortiz P
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- Humans, Middle Aged, Female, Male, Retrospective Studies, Aged, Treatment Outcome, Adult, Time Factors, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Mycosis Fungoides drug therapy, Mycosis Fungoides pathology, Interferon-alpha administration & dosage, Interferon-alpha adverse effects, Interferon-alpha therapeutic use, Recombinant Proteins administration & dosage, Recombinant Proteins adverse effects, Skin Neoplasms drug therapy, Skin Neoplasms pathology, Polyethylene Glycols administration & dosage, Polyethylene Glycols adverse effects, Sezary Syndrome drug therapy, Sezary Syndrome pathology
- Abstract
Background: Mycosis fungoides (MF) and Sézary syndrome (SS) are chronic malignant diseases that typically necessitate diverse strategies to achieve remission. Systemic interferon (IFN)-α (subtypes 2a and 2b) has been used to treat MF/SS since 1984; however, its production was recently stopped. The recombinant pegylated (PEG) form of IFN-α-2a remains the only alternative IFN treatment, although it has not been approved for use in MF/SS., Objectives: To assess the effectiveness and safety of PEG-IFN-α-2a in monotherapy and in combination with other treatments using time to next treatment (TTNT) as a measure of clinical therapeutic benefit in a real-world setting., Methods: We conducted an international, multicentre retrospective study of patients with MF and SS (of any stage) treated with PEG-IFN-α-2a from July 2012 to February 2022. Patients were included across 11 centres in 10 countries. The primary endpoints were to determine the TTNT of PEG-IFN-α-2a and adverse events (AEs) in MF/SS., Results: In total, 105 patients were included [mean (SD) age 61 (13.1) years]; 42 (40.0%) had stage IA-IIA and 63 (60.0%) had stage IIB-IVB disease. PEG-IFN-α-2a was combined with other therapies in 67 (63.8%) patients, most commonly with extracorporeal photopheresis (36%) and bexarotene (22%). Patients with stage I-IIA disease achieved an overall response rate (ORR) of 57%; the ORR in those with stage IIB-IVB disease was 51%. Combination treatment resulted in a median TTNT of 10.4 months (range 0.6-50.7) vs. 7.0 months (range 0.7-52.4) for those who received monotherapy (P < 0.01). Overall, the mean (SD) TTNT was 9.2 (10.6) months and the ORR was 53.3% (n = 56). A complete response was seen in 13% of patients and a partial response in 40%. AEs were described in 68.6% (n = 72) of patients. Flu-like symptoms (n = 28; 26.7%), lymphopenia (n = 24; 22.9%) and elevated liver function (n = 10; 9.5%) were the most frequently reported. Grade 3-4 AEs were reported in 23 (21.9%) patients, mostly related to myelosuppression., Conclusions: PEG-IFN-α-2a for MF/SS resulted in an ORR of 53.3% and a mean (SD) TTNT of 9.2 (10.6) months. Combination regimens were superior to monotherapy and doses of 180 µg PEG-IFN-α-2a weekly were related to a higher ORR., Competing Interests: Conflicts of interest E.H. has received honoraria for consulting and/or lectures from Helsinn, Takeda, Vidac, Recordati and Rafa; and support for travel/meeting participation from Rafa. C.J. has received honoraria for consulting and/or lectures and support for travel/meeting participation from Takeda, Kyowa Kirin and Recordati. J.N. has received honoraria for consulting and/or lectures from Kyowa Kirin, Takeda, Recordati/Helsinn and Mallinckrodt/Therakos; and research funding from Kyowa Kirin. P.Q. has received honoraria for consulting and/or lectures from Takeda, Kyowa Kirin, Recordati/Helsinn, Mallinckrodt and 4SC. J.C.-M. has received honoraria for lectures from Takeda and Janssen. P.O. has received honoraria for lectures from Kyowa, Helsinn, Recordati, Mallinkrodt and 4SC; and support for travel/meeting participation from Kyowa, Almirall and LEO Pharma., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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15. Cutaneous Reactions in Pediatric Patients Treated with MEK Inhibitors: A Retrospective Single-Center Study.
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Friedland R, Glick M, Amitay-Laish I, and Toledano H
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- Humans, Retrospective Studies, Male, Female, Child, Adolescent, Child, Preschool, Pyridones adverse effects, Pyrimidinones adverse effects, Infant, Severity of Illness Index, Imidazoles adverse effects, Oximes adverse effects, Oximes therapeutic use, Benzimidazoles adverse effects, Paronychia chemically induced, Drug Eruptions etiology, Protein Kinase Inhibitors adverse effects, Proto-Oncogene Mas
- Abstract
Introduction: Mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors are in use for several indications for adults and children. Cutaneous toxicities are among the most common adverse effects. We aimed to describe the spectrum of cutaneous adverse events, its frequency, and severity in a cohort of pediatric patients., Methods: We reviewed all records of patients in our tertiary treatment center treated with MEK inhibitors between January 2016 and January 2023 for all indications., Results: Among 33 patients, 76% reported cutaneous adverse effects. The highest prevalence was in the group of patients treated with trametinib (90%), followed by the group treated with selumetinib (50%) and the group treated with a combination of trametinib and B-Raf proto-oncogene serine/threonine-protein kinase inhibitor (dabrafenib, 34%). Xerosis, dermatitis, paronychia, and hair heterochromia were most frequently reported. Severity was graded 1 or 2 for most adverse events, and 237 visits to the dermatology clinic related to these adverse events were recorded., Conclusions: Cutaneous adverse events are common in the pediatric population as in adults, but the clinical spectrum is different. Although considered mild, multiple dermatological consultations reflect the distress caused by these events. Dermatologists have a central role in the multidisciplinary care of pediatric patients receiving these agents., (© 2024 The Author(s). Published by S. Karger AG, Basel.)
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- 2024
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16. mAb14, a Monoclonal Antibody against Cell Surface PCNA: A Potential Tool for Sezary Syndrome Diagnosis and Targeted Immunotherapy.
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Knaneh J, Hodak E, Fedida-Metula S, Edri A, Eren R, Yoffe Y, Amitay-Laish I, Prag Naveh H, Lubin I, Porgador A, and Moyal L
- Abstract
Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common types of primary cutaneous T-cell lymphoma (CTCL). Proliferating cell nuclear antigen (PCNA) is expressed on the cell surface of cancer cells (csPCNA), but not on normal cells. It functions as an immune checkpoint ligand by interacting with natural killer (NK) cells through the NK inhibitory receptor NKp44, leading to the inhibition of NK cytotoxicity. A monoclonal antibody (mAb14) was established to detect csPCNA on cancer cells and block their interaction with NKp44. In this study, three CTCL cell lines and peripheral blood mononuclear cells (PBMCs) from patients with SS and healthy donors were analyzed for csPCNA using mAb14, compared to monoclonal antibody PC10, against nuclear PCNA (nPCNA). The following assays were used: immunostaining, imaging flow cytometry, flow cytometry, cell sorting, cell cycle analysis, ELISA, and the NK-cell cytotoxic assay. mAb14 successfully detected PCNA on the membrane and in the cytoplasm of viable CTCL cell lines associated with the G2/M phase. In the Sézary PBMCs, csPCNA was expressed on lymphoma cells that had an atypical morphology and not on normal cells. Furthermore, it was not expressed on PBMCs from healthy donors. In the co-culture of peripheral blood NK (pNK) cells with CTCL lines, mAb14 increased the secretion of IFN-γ, indicating the reactivation of pNK activity. However, mAb14 did not enhance the cytotoxic activity of pNK cells against CTCL cell lines. The unique expression of csPCNA detected by mAb14 suggests that csPCNA and mAb14 may serve as a potential biomarker and tool, respectively, for detecting malignant cells in SS and possibly other CTCL variants.
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- 2023
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17. Mycosis Fungoides in Solid-Organ Transplant Recipients: A Multicenter Retrospective Cohort Study.
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Amitay-Laish I, Didkovsky E, Davidovici B, Friedland R, Ben Amitai D, Landov H, Greenberger S, Ollech A, Prag Naveh H, Hodak E, and Barzilai A
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- Child, Humans, Male, Adolescent, Retrospective Studies, Acitretin, Prednisone, Tacrolimus adverse effects, Mycosis Fungoides pathology, Skin Neoplasms pathology, Organ Transplantation adverse effects
- Abstract
Background: Mycosis fungoides (MF) in solid-organ transplant recipients (SOTRs) is rare, with limited data on disease characteristics., Objective: The aim was to study the characteristics of MF in SOTRs with an emphasis on the immunosuppressive therapy., Methods: A retrospective cohort of patients diagnosed with MF, who were also SOTRs, were followed at 3 cutaneous lymphoma outpatient clinics, between January 2010 and February 2022., Results: Ten patients were included (7 male; median ages at transplantation and at diagnosis of MF were 33 and 48 years, respectively; 40% were diagnosed before the age of 18 years). Median time from transplantation to diagnosis of MF was 8 years (range 0.5-22). Transplanted organs and immunosuppressive treatments included: liver (n = 5; 4 treated with tacrolimus, 1 with tacrolimus and prednisone), kidney (n = 3), liver and kidney (n = 1), and heart (n = 1), all treated with mycophenolic acid, tacrolimus, and prednisone. Nine had early-stage MF (IA - 4, IB - 5; 40% with early folliculotropic MF), treated with skin-directed therapies, in 2 combined with acitretin, achieving partial/complete response. One patient had advanced-stage MF (IIIA) with folliculotropic erythroderma, treated with ultraviolet A and narrow-band ultraviolet B with acitretin, achieving partial response. Immunosuppression was modified in 3. At last follow-up (median 4 years, range 1-8), no stage progression was observed; 5 had no evidence of disease, 5 had active disease (IA/IB - 4, III - 1)., Conclusions: MF in SOTRs is usually diagnosed at an early stage, with overrepresentation of folliculotropic MF, and of children. Immunosuppressive therapy alterations, not conducted in most patients, should be balanced against the risk of organ compromise/rejection. Disease course was similar to MF in immunocompetent patients, during the limited time of follow-up., (© 2023 S. Karger AG, Basel.)
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- 2023
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18. Facial demodicosis in the immunosuppressed state: a retrospective case series from a tertiary referral center.
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Amitay-Laish I, Solomon-Cohen E, Feuerman H, Didkovsky E, Davidovici B, Leshem YA, Pavlovsky L, Reiter O, Mimouni D, Hodak E, and Segal R
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- Animals, Female, Humans, Male, Middle Aged, Prednisone therapeutic use, Retrospective Studies, Tertiary Care Centers, Tumor Necrosis Factor Inhibitors, Mite Infestations diagnosis, Mite Infestations drug therapy, Mites, Rosacea diagnosis, Rosacea drug therapy
- Abstract
Background: Data on Demodex in the immunosuppressed state is limited, focusing mainly on patients with human immunodeficiency virus and hematological malignancies. The aim of this study was to describe the manifestations of facial demodicosis in diverse immunosuppressive states., Methods: The medical records of all patients followed at a Demodex outpatient clinic of a tertiary medical center from January 2008 to November 2020 were retrospectively reviewed. Data on patients who were immunosuppressed while with demodicosis were retrieved., Results: The cohort included 28 patients (17 women and 11 men; median age, 58 years). Types of immunosuppression included treatments with hydroxyurea for polycythemia vera/essential thrombocytosis, mycophenolic acid, tacrolimus, and prednisone for liver and/or kidney transplantation, prednisone with cyclosporine/methotrexate/azathioprine/rituximab mainly for autoimmune diseases, mercaptopurine with/without anti-tumor necrosis factor alpha (TNF-α) for Crohn's disease, chemotherapy for neoplasms, anti-TNF-α for psoriasis, and Cushing's syndrome. The clinical types of demodicosis included: papulopustular, erythematotelangiectatic and fulminant rosacea, hyperpigmented, pityriasis folliculorum, pustular folliculitis, and dermatitis. The diverse clinical presentations led to various differential diagnoses. Topical treatment with ivermectin (monotherapy/combination with other treatments) was effective., Conclusion: Clinicians treating immunosuppressed patients should be familiar with the different forms of demodicosis and include them in the differential diagnosis of facial eruptions., (© 2022 the International Society of Dermatology.)
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- 2022
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19. Real-life experience with chlormethine gel for early-stage mycosis fungoides with emphasis on types and management of cutaneous side-effects .
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Prag Naveh H, Amitay-Laish I, Zidan O, Leshem YA, Sherman S, Noyman Y, Taieb J, Didkovsky E, and Hodak E
- Subjects
- Adult, Humans, Mechlorethamine adverse effects, Retrospective Studies, Dermatitis, Contact drug therapy, Dermatologic Agents therapeutic use, Drug-Related Side Effects and Adverse Reactions, Mycosis Fungoides drug therapy, Skin Neoplasms drug therapy
- Abstract
Background: Real-life efficacy data on the recently approved once daily application of chlormethine gel (CG) for mycosis fungoides (MF) is limited, and detailed characterization of the side effects and their management are strikingly sparse., Objective: To evaluate the efficacy and particularly the side effect profile of CG in early-stage MF patients in a real-life setting., Methods: We performed a single-center retrospective analysis of 66 early-stage MF adult patients treated with CG in 2016-2019., Results: Treatment with a once-daily application (52%), or at lower frequencies (48%), in some with topical corticosteroids (TCS) (40%), resulted in an overall response rate of 50%, with no significant difference between stage IA and IB. Cutaneous side effects (56%) included irritant or allergic contact dermatitis (36%, mostly mild/moderate and manageable by reducing application frequency and/or adding TCS or interrupting treatment), unmasking effect (9%), hyperpigmentation (14%), and pruritus (9%). Withdrawal due to side effects occurred in 19.6% of patients (15% for contact dermatitis)., Conclusion: In real-life management, flexible regimens of CG sometimes with TCS, show efficacy in early-stage MF and may reduce the rate of contact dermatitis, the main treatment-limiting side effect. Practical recommendations with emphasis of the types, time of appearance, and management of side effects are provided.
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- 2022
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20. New developments in skin-directed treatments of cutaneous T-cell lymphoma.
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Amitay-Laish I and Hodak E
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- Administration, Cutaneous, Humans, Lymphoma, T-Cell, Cutaneous pathology, Lymphoma, T-Cell, Cutaneous therapy, Mycosis Fungoides therapy, Skin Neoplasms pathology, Skin Neoplasms therapy
- Abstract
The therapeutic approach for mycosis fungoides, the most common type of primary cutaneous T-cell lymphoma, is based mainly on the stage of the disease, and skin-directed treatment is recommended by all international guidelines as the first-line of treatment for early-stage disease. Skin-directed treatments may be also given in combination with systemic therapies in early-stage mycosis fungoides patients recalcitrant to different types of skin-directed treatments, or in certain patients with high-risk features. Advanced-stage mycosis fungoides is treated mainly with systemic treatments, which may be combined with skin-directed treatments. Due to the rarity of mycosis fungoides, controlled clinical trials of the different skin-directed treatment modalities are almost non-existent, with a few exceptions, and therefore recommendations are largely based on cohort studies and expert opinion. This paper reviews the new developments in skin-directed treatments and provides an update on new studies of already well-known therapies, and an update on novel treatments., (Copyright © 2022.)
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- 2022
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21. New Insights into Macular Type of Primary Cutaneous B-Cell Lymphoma: Extension of the Clinical and Histopathological Patterns.
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Barzilai A, Amitay-Laish I, Didkovsky E, Feinmesser M, Dalal A, Schiby G, and Hodak E
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- Humans, Retrospective Studies, Erythema, Skin Neoplasms pathology, Lymphoma, B-Cell, Marginal Zone diagnosis
- Abstract
Background: Primary cutaneous B-cell lymphoma (PCBCL) classically presents with papules, plaques, and nodules/tumors. Previous reports of PCBCL manifesting with macular lesions are scarce and focused on primary cutaneous follicle-center cell lymphoma (PCFCL)., Objectives: The objective of this study was to report our experience with PCBCL presenting with erythematous macules., Methods: Patients with low-grade PCBCL manifesting with erythematous patches, diagnosed and managed between January 2000 through December 2019 at 2 tertiary cutaneous-lymphoma outpatient clinics, were included. Clinical data were retrospectively collected, and biopsy specimens of the macules, and if present of the typical nodular/tumoral lesions, were reviewed., Results: There were 14 patients, aged 16-67 years, 8 had PCFCL and 6 marginal zone lymphoma (PCMZL). All had 1-15 cm erythematous macules, mimicking: interstitial granuloma annulare/vascular tumors/early-stage folliculotropic mycosis fungoides, or presenting with figurate erythema or livedo reticularis-like/net-like pattern. In 3 patients, macules were the presenting lesions, in 2 as the sole manifestation, whereas in 12 patients, typical PCBCL lesions were observed during disease course. The macules showed in all, superficial and deep perivascular infiltrates, and in most, periadnexal infiltrates. Micronodules were observed in 11 specimens, with nodular infiltrates also observed in 4. B cells comprised the majority of the lymphocytes in only 4. Seven of 11 cases tested showed immunoglobulin heavy chain monoclonality., Conclusions: PCMZL and PCFCL may manifest with erythematous macules. Physicians should be aware of this unusual manifestation of low-grade PCBCL, which may represent a clinicopathological diagnostic pitfall., (© 2022 The Author(s). Published by S. Karger AG, Basel.)
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- 2022
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22. Clinical approach to skin eruptions induced by anti-TNF agents among patients with inflammatory bowel diseases: insights from a multidisciplinary IBD-DERMA clinic.
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Yanai H, Amir Barak H, Ollech JE, Avni Biron I, Goren I, Snir Y, Banai Eran H, Broitman Y, Aharoni Golan M, Didkovsky E, Amitay-Laish I, Ollech A, Hodak E, Dotan I, and Pavlovsky L
- Abstract
Background and Aims: Skin eruptions are prevalent among patients with inflammatory bowel diseases (IBD), often associated with therapies and frequently leading to dermatological consults and treatment interruptions. We aimed to assess the impact of joint shared decision-making in a multidisciplinary (MDT) IBD-DERMA clinic., Methods: This retrospective cohort study assessed a consecutive group of patients with IBD who were referred for consultation in an MDT clinic at a tertiary referral center in Israel., Results: Over 1 year, 118 patients were evaluated in the MDT-IBD-DERMA clinic: 68 (57.6%) males; age - 35.2 ± 13.5 years, disease duration - 7.1 (interquartile range: 3.7-13.9) years; Crohn's disease - 94/118 (79.6%). Skin eruption induced by an anti-tumor necrosis factor (TNF) were the most common diagnoses [46/118 (39%)], including psoriasiform dermatitis (PD) - 31/46 (67.4%) and inflammatory alopecia (IA) - 15/46 (32.6%). Of these, 18 patients (39.1%) continued the anti-TNF agent concomitantly with a topical or systemic anti-inflammatory agent to control the eruption. The remaining 28 patients (60.9%) discontinued the anti-TNF, of whom 16/28 (57.1%) switched to ustekinumab. These strategies effectively treated the majority [38/46 (82.6%)] of patients. Continuation of the anti-TNF was possible in a significantly higher proportion of patients with PD: 12/31 (38.7%) than only one in the IA group, p = 0.035. There was a higher switch to ustekinumab among the IA 7/15 (46.6%) compared with the PD 7/31 (22.6%) group, P = .09. Following IBD-DERMA advised intervention, IBD deteriorated in 9/4 6(19.5%) patients, 5/9 on ustekinumab (PD versus IA, P = NS)., Conclusion: Shared decision-making in an integrated IBD-DERMA clinic allowed successful control of skin eruptions while preserving control of the underlying IBD in more than 80% of cases. Patients with IA profited from a switch to ustekinumab., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Henit Yanai: reports institutional research grants from Pfizer; consulting fees from Abbvie, Ferring, Janssen, Neopharm Ltd., Pfizer, Takeda; honoraria for lectures from Abbvie, Janssen, Pfizer, Takeda; participation on a Data Safety Monitoring Board or Advisory Board from Abbvie, Neopharm Ltd., Pfizer, Takeda. Hadar Amir Barak: none. Jacob E Ollech: none. Irit Avni Biron: none. Idan Goren: reports institutional research grants from Pfizer. Yifat Snir: none. Hagar Banai Eran: none. Yelena Broitman: none. Maya Aharoni Golan: none. Elena Didkovsky: none. Iris Amitay-Laish: none. Ayelet Ollech: none. Emmilia Hodak: none relevant. Iris Dotan: research grants from Altman Research, Pfizer; Advisory board/consulting fees: Pfizer, Janssen, Abbvie, Takeda, Genentech/Roche, Arena, Neopharm, Gilead, Galapagos, Celltrion, Rafa Laboratories, Ferring, DSM, Cambridge Healthcare, Sublimity, Sangamo, Wild Biotech, Food industries organization, Integra Holdings, Celgene/BMS, Abbott, 89 Bio, Alimentiv; Speakers Bureau: Roche/Genentech, Falk Pharma, Abbvie, Janssen, Pfizer, Takeda Neopharm, Celltrion, Ferring, Nestle, Celgene/BMS. Lev Pavlovsky has served as an investigator for Abbvie, Coherus, Novartis Pharmaceuticals Corporation, Janssen Biotech, Eli Lilly, Bristol Myers Squibb and as an advisor, consultant, and/or invited lecturer for Abbvie, Janssen Biotech, Novartis Pharmaceuticals Corporation, Pfizer Inc., Dexcel Pharma, Eli Lilly, and Boehringer Ingelheim., (© The Author(s), 2021.)
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- 2021
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23. The trichoscopic features of hair shaft anomalies induced by epidermal growth factor receptor inhibitors: A case series.
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Kremer N, Martinez H, Leshem YA, Hodak E, Zer A, Brenner B, and Amitay-Laish I
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- Aged, ErbB Receptors, Female, Humans, Male, Protein Kinase Inhibitors, Scalp, Dermoscopy, Hair Diseases chemically induced, Hair Diseases diagnostic imaging
- Abstract
Background: Although the clinical hair changes that occur under treatment with epidermal growth factor receptor inhibitors (EGFRIs) are documented, their trichoscopic features have not been reported., Objective: To evaluate the trichoscopic findings in scalp and facial hair, induced by EGFRI treatment., Methods: Patients treated with EGFRIs at a tertiary oncodermatology clinic in 2015 through 2017 were evaluated for macroscopic and trichoscopic changes., Results: The cohort included 23 patients (13 women; median age, 68 years) treated with EGFRIs for an average of 13 months (range, 2-40 months). Macroscopically, 18 patients (78%) had dry, lusterless, coarse, kinky, brittle scalp hair, and 17 (74%) had trichomegaly of the eyebrows/eyelashes. Trichoscopic findings were of hair shaft anomalies including pili torti, affecting scalp hair in 20 patients (87%), eyebrows in 6 (26%), and eyelashes in 8 (50%), and asymmetric hyperpigmented fusiform widening of hair scalp in 3 (13%), eyebrows in 10 (43%), and eyelashes in 4 (25%). Dermoscopic findings of the peri- and interfollicular skin were scale, whitish erythematous structureless areas, and branching vessels., Limitations: Lack of trichoscopic-histologic correlation, lack of baseline examination., Conclusion: The trichoscopic correlates of the macroscopic hair changes under EFGRI treatment include pili torti, and asymmetric hyperpigmented fusiform widening, with dermoscopic cutaneous manifestations of scale, whitish erythematous structureless areas, and branching vessels., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)
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- 2021
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24. Treatment of early-stage mycosis fungoides: results from the PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study.
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Quaglino P, Prince HM, Cowan R, Vermeer M, Papadavid E, Bagot M, Servitjie O, Berti E, Guenova E, Stadler R, Querfeld C, Busschots AM, Hodak E, Patsatsi A, Sanches J, Maule M, Yoo J, Kevin M, Fava P, Ribero S, Zocchi L, Rubatto M, Fierro MT, Wehkamp U, Marshalko M, Mitteldorf C, Akilov O, Ortiz-Romero P, Estrach T, Vakeva L, Enz PA, Wobser M, Bayne M, Jonak C, Rubeta M, Forbes A, Bates A, Battistella M, Amel-Kashipaz R, Vydianath B, Combalia A, Georgiou E, Hauben E, Hong EK, Jost M, Knobler R, Amitay-Laish I, Miyashiro D, Cury-Martins J, Martinez X, Muniesa C, Prag-Naveh H, Stratigos A, Nikolaou V, Quint K, Ram-Wolff C, Rieger K, Stranzenbach R, Szepesi Á, Alberti-Violetti S, Felicity E, Cerroni L, Kempf W, Whittaker S, Willemze R, Kim Y, and Scarisbrick JJ
- Subjects
- Humans, Neoplasm Staging, Prognosis, Prospective Studies, Quality of Life, Mycosis Fungoides pathology, Mycosis Fungoides therapy, Skin Neoplasms pathology, Skin Neoplasms therapy
- Abstract
Background: The PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study is a prospective analysis of an international database. Here we examine front-line treatments and quality of life (QoL) in patients with newly diagnosed mycosis fungoides (MF)., Objectives: To identify (i) differences in first-line approaches according to tumour-nodes-metastasis-blood (TNMB) staging; (ii) parameters related to a first-line systemic approach and (iii) response rates and QoL measures., Methods: In total, 395 newly diagnosed patients with early-stage MF (stage IA-IIA) were recruited from 41 centres in 17 countries between 1 January 2015 and 31 December 2018 following central clinicopathological review., Results: The most common first-line therapy was skin-directed therapy (SDT) (322 cases, 81·5%), while a smaller percentage (44 cases, 11·1%) received systemic therapy. Expectant observation was used in 7·3%. In univariate analysis, the use of systemic therapy was significantly associated with higher clinical stage (IA, 6%; IB, 14%; IIA, 20%; IA-IB vs. IIA, P < 0·001), presence of plaques (T1a/T2a, 5%; T1b/T2b, 17%; P < 0·001), higher modified Severity Weighted Assessment Tool (> 10, 15%; ≤ 10, 7%; P = 0·01) and folliculotropic MF (FMF) (24% vs. 12%, P = 0·001). Multivariate analysis demonstrated significant associations with the presence of plaques (T1b/T2b vs. T1a/T2a, odds ratio 3·07) and FMF (odds ratio 2·83). The overall response rate (ORR) to first-line SDT was 73%, while the ORR to first-line systemic treatments was lower (57%) (P = 0·027). Health-related QoL improved significantly both in patients with responsive disease and in those with stable disease., Conclusions: Disease characteristics such as presence of plaques and FMF influence physician treatment choices, and SDT was superior to systemic therapy even in patients with such disease characteristics. Consequently, future treatment guidelines for early-stage MF need to address these issues., (© 2020 British Association of Dermatologists.)
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- 2021
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25. Cancer-Associated Fibroblasts in Mycosis Fungoides Promote Tumor Cell Migration and Drug Resistance through CXCL12/CXCR4.
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Aronovich A, Moyal L, Gorovitz B, Amitay-Laish I, Naveh HP, Forer Y, Maron L, Knaneh J, Ad-El D, Yaacobi D, Barel E, Erez N, and Hodak E
- Subjects
- Adult, Aged, Aged, 80 and over, Apoproteins drug effects, Apoproteins immunology, Biopsy, Cancer-Associated Fibroblasts metabolism, Case-Control Studies, Cell Line, Tumor, Cell Movement drug effects, Cell Movement immunology, Cell Transformation, Neoplastic immunology, Cells, Cultured, Chemokine CXCL12 antagonists & inhibitors, Coculture Techniques, Doxorubicin pharmacology, Doxorubicin therapeutic use, Drug Resistance, Neoplasm immunology, Female, Healthy Volunteers, Humans, Male, Middle Aged, Mycosis Fungoides drug therapy, Mycosis Fungoides pathology, Primary Cell Culture, Receptors, CXCR4 antagonists & inhibitors, Signal Transduction drug effects, Signal Transduction immunology, Skin cytology, Skin pathology, Skin Neoplasms drug therapy, Skin Neoplasms pathology, Tumor Microenvironment drug effects, Tumor Microenvironment immunology, Young Adult, Cancer-Associated Fibroblasts immunology, Chemokine CXCL12 metabolism, Mycosis Fungoides immunology, Receptors, CXCR4 metabolism, Skin Neoplasms immunology
- Abstract
Cancer cells are known to reprogram normal fibroblasts into cancer-associated fibroblasts (CAFs) to act as tumor supporters. The presence and role of CAFs in mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma, are unknown. This study sought to characterize CAFs in MF and their cross talk with the lymphoma cells using primary fibroblast cultures from punch biopsies of patients with early-stage MF and healthy subjects. MF cultures yielded significantly increased levels of FAPα, a CAF marker, and CAF-associated genes and proteins: CXCL12 (ligand of CXCR4 expressed on MF cells), collagen XI, and matrix metalloproteinase 2. Cultured MF fibroblasts showed greater proliferation than normal fibroblasts in ex vivo experiments. A coculture with MyLa cells (MF cell line) increased normal fibroblast growth, reduced the sensitivity of MyLa cells to doxorubicin, and enhanced their migration. Inhibiting the CXCL12/CXCR4 axis increased doxorubicin-induced apoptosis of MyLa cells and reduced MyLa cell motility. Our data suggest that the fibroblasts in MF lesions are more proliferative than fibroblasts in normal skin and that CAFs protect MF cells from doxorubicin-induced cell death and increase their migration through the secretion of CXCL12. Reversing the CAF-mediated tumor microenvironment in MF may improve the efficiency of anticancer therapy., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2021
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26. Should we be imaging lymph nodes at initial diagnosis of early-stage mycosis fungoides? Results from the PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) international study.
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Hodak E, Sherman S, Papadavid E, Bagot M, Querfeld C, Quaglino P, Prince HM, Ortiz-Romero PL, Stadler R, Knobler R, Guenova E, Estrach T, Patsatsi A, Leshem YA, Prague-Naveh H, Berti E, Alberti-Violetti S, Cowan R, Jonak C, Nikolaou V, Mitteldorf C, Akilov O, Geskin L, Matin R, Beylot-Barry M, Vakeva L, Sanches JA, Servitje O, Weatherhead S, Wobser M, Yoo J, Bayne M, Bates A, Dunnill G, Marschalko M, Buschots AM, Wehkamp U, Evison F, Hong E, Amitay-Laish I, Stranzenbach R, Vermeer M, Willemze R, Kempf W, Cerroni L, Whittaker S, Kim YH, and Scarisbrick JJ
- Subjects
- Humans, Lymph Nodes diagnostic imaging, Lymph Nodes pathology, Neoplasm Staging, Prognosis, Prospective Studies, Mycosis Fungoides diagnostic imaging, Mycosis Fungoides pathology, Skin Neoplasms diagnostic imaging, Skin Neoplasms pathology
- Abstract
Background: Early-stage mycosis fungoides (MF) includes involvement of dermatopathic lymph nodes (LNs) or early lymphomatous LNs. There is a lack of unanimity among current guidelines regarding the indications for initial staging imaging in early-stage presentation of MF in the absence of enlarged palpable LNs., Objectives: To investigate how often imaging is performed in patients with early-stage presentation of MF, to assess the yield of LN imaging, and to determine what disease characteristics promoted imaging., Methods: A review of clinicopathologically confirmed newly diagnosed patients with cutaneous patch/plaque (T1/T2) MF from PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) data., Results: PROCLIPI enrolled 375 patients with stage T1/T2 MF: 304 with classical MF and 71 with folliculotropic MF. Imaging was performed in 169 patients (45%): 83 with computed tomography, 18 with positron emission tomography-computed tomography and 68 with ultrasound. Only nine of these (5%) had palpable enlarged (≥ 15 mm) LNs, with an over-representation of plaques, irrespectively of the 10% body surface area cutoff that distinguishes T1 from T2. Folliculotropic MF was not more frequently imaged than classical MF. Radiologically enlarged LNs (≥ 15 mm) were detected in 30 patients (18%); only seven had clinical lymphadenopathy. On multivariate analysis, plaque presentation was the sole parameter significantly associated with radiologically enlarged LNs. Imaging of only clinically enlarged LNs upstaged 4% of patients (seven of 169) to at least IIA, whereas nonselective imaging upstaged another 14% (24 of 169). LN biopsy, performed in eight of 30 patients, identified N3 (extensive lymphomatous involvement) in two and N1 (dermatopathic changes) in six., Conclusions: Physical examination was a poor determinant of LN enlargement or involvement. Presence of plaques was associated with a significant increase in identification of enlarged or involved LNs in patients with early-stage presentation of MF, which may be important when deciding who to image. Imaging increases the detection rate of stage IIA MF, and identifies rare cases of extensive lymphomatous nodes, upstaging them to advanced-stage IVA2., (© 2020 British Association of Dermatologists.)
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- 2021
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27. Prophylactic Topical Treatment for EGFR Inhibitor-Induced Papulopustular Rash: A Randomized Clinical Trial.
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Amitay-Laish I, Prag-Naveh H, Ollech A, Davidovici B, Leshem YA, Snast I, Popovtzer A, Purim O, Flex D, David M, Brenner B, Ben-Aharon I, Peled N, Hodak E, and Stemmer SM
- Subjects
- Administration, Topical, Adult, Aged, Aged, 80 and over, Anti-Inflammatory Agents therapeutic use, Double-Blind Method, Exanthema chemically induced, Female, Humans, Male, Middle Aged, Neoplasms drug therapy, Neoplasms pathology, Prednisolone therapeutic use, Anti-Bacterial Agents therapeutic use, Chloramphenicol therapeutic use, ErbB Receptors adverse effects, ErbB Receptors antagonists & inhibitors, Exanthema prevention & control, Protein Kinase Inhibitors adverse effects
- Abstract
Background: The incidence of epidermal growth factor receptor inhibitor (EGFRI)-induced papulopustular rash is 60-85%., Objective: To investigate prophylactic topical treatment for EGFRI-induced rash., Methods: A single-center, randomized, double-blind, placebo-controlled trial. Adult cancer patients initiating treatment with EGFRIs were randomized to receive facial topical treatment with chloramphenicol 3% + prednisolone 0.5% (CHL-PRED) ointment, chloramphenicol 3% (CHL) ointment, or aqua cream (AQUA). The primary end points were the incidence of ≥grade 3 rash using the Common Terminology Criteria for Adverse Events (CTCAE), on days 14 and 30. A subanalysis was conducted for incidence of a protocol-specified significant rash, defined as ≥10 facial papulopustular lesions., Results: The per-protocol analysis on day 14 included 69 patients, who received CHL-PRED (21), CHL (23), or AQUA (25). The incidence of CTCAE ≥grade 3 rash was not statistically significant between arms; however, the incidence of the protocol-specified significant rash was: CHL-PRED 14%, CHL 39%, and AQUA 48% (p = 0.03, CHL-PRED vs. AQUA). At 30 days, the CTCAE ≥grade 3 incidence was similar, but the incidences of protocol-specified significant rash were 6%, 16%, and 43% (p = 0.03, CHL-PRED vs. AQUA). No significant differences were found between CHL and CHL-PRED and between CHL and AQUA., Conclusions: Prophylactic topical CHL-PRED was efficacious when compared to AQUA, in the treatment of EGFRI-induced facial papulopustular rash., (© 2020 S. Karger AG, Basel.)
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- 2021
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28. Ixekizumab Survival in Heavily Pretreated Patients with Psoriasis: A Two-year Single-centre Retrospective Study.
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Sherman S, Zloczower O, Noyman Y, Amitay-Laish I, Hodak E, and Pavlovsky L
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- Antibodies, Monoclonal, Humanized, Humans, Retrospective Studies, Severity of Illness Index, Treatment Outcome, Psoriasis diagnosis, Psoriasis drug therapy
- Abstract
The long-term effect of intra-anti-interleukin-17-class switch on drug survival is unclear. The aim of this study was to evaluate the efficacy and long-term survival of ixekizumab in bio-experienced psoriatic patients with and without previous exposure to anti-interleukin-17 treatment. Retrospective search of a tertiary medical centre database for 2017 to 2019 yielded 73 patients treated with ixekizumab: 50 previously exposed to secukinumab and 23 anti-interleukin-17-naïve. Median baseline Psoriasis Area Severity Index (PASI) was 23.0. Median number of received biologics was 4. Mean drug survival was 16.4 and 16.8 months in the anti-interleukin-17-exposed and naïve groups, respectively (p = 0.878). There was no between-group difference in proportion of patients achieving ≥ 75 PASI response. At study end, 25 anti-interleukin-17-exposed patients (50.0%) and 17 anti-interleukin-17-naïve patients (73.9%) were still on ixekizumab. The use of multiple previous biologic treatments was associated with substantially reduced ixekizumab survival. In conclusion, previous anti-interleukin-17-exposure was associated with an initially favourable response and did not further reduce ixekizumab survival.
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- 2020
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29. Melanoma Risk is Increased in Patients with Mycosis Fungoides Compared with Patients with Psoriasis and the General Population.
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Sherman S, Kremer N, Dalal A, Solomon-Cohen E, Berkovich E, Noyman Y, Ben-Lassan M, Levi A, Pavlovsky L, Prag Naveh H, Hodak E, and Amitay-Laish I
- Subjects
- Humans, Retrospective Studies, Melanoma diagnosis, Melanoma epidemiology, Mycosis Fungoides diagnosis, Mycosis Fungoides epidemiology, Psoriasis diagnosis, Psoriasis epidemiology, Skin Neoplasms diagnosis, Skin Neoplasms epidemiology, Skin Neoplasms therapy
- Abstract
Patients with mycosis fungoides (MF) are thought to be at increased risk of melanoma. However, studies addressing surveillance-bias and treatments as a possible confounder are lacking. This retrospective study compared the prevalence and risk of melanoma between 982 patients with MF, and 3,165 patients with psoriasis attending tertiary cutaneous-lymphoma/psoriasis clinics during 2009 to 2018. Melanoma was diagnosed in 47 patients with MF (4.8%; 43 early-stage) and in 23 patients with psoriasis (0.7%) (odds ratio 6.6, p < 0.0001). In 60% of patients, MF/psoriasis preceded melanoma diagnosis. Hazard ratio (HR) for a subsequent melanoma in MF vs psoriasis was 6.3 (95% confidence interval (95% CI) 3.4-11.7, p < 0.0001). Compared with the general population, melanoma standardized incidence ratios were 17.5 in patients with MF (95% CI 11.0-23.9, p < 0.0001), and 2.2 (95% CI 0.6-3.8, p = 0.148) in patients with psoriasis. Narrow-band ultraviolet B was not a contributory factor (HR 1.15, 95% CI 0.62-2.14, p = 0.66). These findings add evidence that patients with MF have a significantly higher risk of melanoma, not only compared with the general population, but also compared with patients with psoriasis. This comorbidity may be inherent to MF.
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- 2020
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30. The Course of Mycosis Fungoides under Cytokine Pathway Blockers: A Multicentre Analysis of Real-life Clinical Data.
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Amitay-Laish I, Guenova E, Ortiz-Romero PL, Vico-Alonso C, Rozati S, Geskin LJ, Nikolaou V, Papadavid E, Barzilai A, Pavlovsky L, Didkovsky E, Naveh HP, Akilov OE, and Hodak E
- Subjects
- Cytokines, Humans, Interleukins, Retrospective Studies, Mycosis Fungoides diagnosis, Mycosis Fungoides drug therapy, Skin Neoplasms drug therapy
- Abstract
Literature regarding the effect of biologics on the course of mycosis fungoides (MF) is scarce. This multicentre study analysed retrospective data on 19 patients with MF, who were treated with biologics; 12 for inflammatory conditions coexisting with MF, and 7 for MF misdiagnosed as an inflammatory skin disease. Eight patients were treated with anti-tumour necrosis factor-α-monotherapy; 6 had early-stage MF, in 3 patients MF preceded and in 3 MF was diagnosed after initiation of biologics, with no stage-progression or with stable disease, respectively (median treatment time concurrent with MF 57 months). Two patients had advanced stage MF: IIB, treated for 15 months with no stage-progression, and IVA1, treated for 8 months, died of disease 10 months later. The other 11/19 patients received anti-interleukin-17A and/or anti-interleukin-12/23 or anti-interleukin-23 (with/without anti-tumour necrosis factor-α/anti-interleukin-4/13), with stage-progression in 8 patients after a median of 8 months' treatment. Although, in general, biologics should be avoided in patients with MF, these results indicate that anti-tumour necrosis factor-α-monotherapy might not aggravate the disease course in early-stage patients. Interleukin-17A, interleukin-12/23 and interleukin-23 pathway-blockers may prompt progression of MF.
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- 2020
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31. Stage-dependent Increase in Expression of miR-155 and Ki-67 and Number of Tumour-associated Inflammatory Cells in Folliculotropic Mycosis Fungoides.
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Atzmony L, Moyal L, Feinmesser M, Gorovitz B, Hirshberg A, Amitay-Laish I, Prag-Naveh H, Barzilai A, and Hodak E
- Subjects
- Biopsy, Humans, Ki-67 Antigen, MicroRNAs genetics, Mycosis Fungoides genetics, Skin Neoplasms genetics
- Abstract
Recent studies suggest that folliculotropic mycosis fungoides (FMF), the most common variant of mycosis fungoides (MF), presents with 2 distinct clinicopathological stages: early indolent stage and more aggressive advanced/tumour stage. To further characterize these stages, miR-155 expression was studied with qRT-PCR and found to be significantly higher in biopsies of tumour-stage FMF compared with early-stage FMF and inflammatory dermatoses. There was no statistically significant difference in miR-155 expression between early-stage FMF and early-stage MF, nor between tumour-stage FMF and tumour-stage MF. Immunohistochemical analysis revealed a significantly increased number of dermal Ki-67+ proliferating lymphocytes in tumour-stage FMF, together with an increased number of CD20+ B cells and CD68+ macrophages compared with early-stage FMF. Thus, similar to classic MF, miR-155, Ki-67 tumour cell immunoreactivity, and certain tumour-infiltrating inflammatory cells are differentially expressed in early- vs tumour-stage FMF. The results of this study corroborate the notion that FMF presents with 2 distinct stages.
- Published
- 2020
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32. Synergistic cytotoxic activity of cannabinoids from cannabis sativa against cutaneous T-cell lymphoma (CTCL) in-vitro and ex-vivo .
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Mazuz M, Tiroler A, Moyal L, Hodak E, Nadarajan S, Vinayaka AC, Gorovitz-Haris B, Lubin I, Drori A, Drori G, Cauwenberghe OV, Faigenboim A, Namdar D, Amitay-Laish I, and Koltai H
- Abstract
Cannabis sativa produces hundreds of phytocannabinoids and terpenes. Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL), characterized by patches, plaques and tumors. Sézary is a leukemic stage of CTCL presenting with erythroderma and the presence of neoplastic Sézary T-cells in peripheral blood. This study aimed to identify active compounds from whole cannabis extracts and their synergistic mixtures, and to assess respective cytotoxic activity against CTCL cells. Ethanol extracts of C. sativa were analyzed by high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GC/MS). Cytotoxic activity was determined using the XTT assay on My-La and HuT-78 cell lines as well as peripheral blood lymphocytes from Sézary patients (SPBL). Annexin V assay and fluorescence-activated cell sorting (FACS) were used to determine apoptosis and cell cycle. RNA sequencing and quantitative PCR were used to determine gene expression. Active cannabis compounds presenting high cytotoxic activity on My-La and HuT-78 cell lines were identified in crude extract fractions designated S4 and S5, and their synergistic mixture was specified. This mixture induced cell cycle arrest and cell apoptosis; a relatively selective apoptosis was also recorded on the malignant CD4
+ CD26- SPBL cells. Significant cytotoxic activity of the corresponding mixture of pure phytocannabinoids further verified genuine interaction between S4 and S5. The gene expression profile was distinct in My-La and HuT-78 cells treated with the S4 and S5 synergistic mixture. We suggest that specifying formulations of synergistic active cannabis compounds and unraveling their modes of action may lead to new cannabis-based therapies., Competing Interests: CONFLICTS OF INTEREST Research was funded by MedC Biopharma Corporation. Since AD, GD, OVC are employees of MedC Biopharma Corporation, there is a conflict of interest for them. However MM, AT, LM, EH, SNR, ACV, BGH, IL, AF, DN, IAL and HK are not employees of the company and have no financial or personal relationships with MedC Biopharma Corporation and therefore have no conflict of interest. There was no compromise in investigators’ judgement in conducting or reporting this research results. The research results are serving now as a base for product development by MedC Biopharma Corporation for the treatment of CTCL.- Published
- 2020
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33. The Utility of 18F-fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography in Cutaneous B-Cell Lymphoma.
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Feuerman H, Snast I, Amitay-Laish I, Bairey O, Barzilai A, Feinmesser M, Mimouni D, Even-Sapir E, and Hodak E
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Reproducibility of Results, Retrospective Studies, Sensitivity and Specificity, Skin diagnostic imaging, Young Adult, Fluorodeoxyglucose F18, Lymphoma, B-Cell diagnostic imaging, Positron Emission Tomography Computed Tomography methods, Radiopharmaceuticals, Skin Neoplasms diagnostic imaging
- Abstract
Background: Whole-body integrated positron emission tomography / contrast-enhanced computed tomography (PET/CT) scan is increasingly used in cutaneous lymphomas. However, the value of PET/CT in the detection of cutaneous lesions in primary cutaneous B-cell lymphoma (PCBCL) has barely been investigated., Objectives: To investigate the diagnostic accuracy of PET/CT in tracking cutaneous involvement in PCBCL., Methods: A retrospective study was conducted on 35 consecutive patients diagnosed with cutaneous B-cell lymphoma according to the World Health Organization classification who were evaluated with PET/CT as the initial staging procedure before treatment., Results: Thirty-five patients met the study criteria. In two patients extracutaneous disease was detected by PET/CT and CT and confirmed by biopsy. Of the 33 patients with PCBCL, 26 (79%) had small cell PCBCL (18 marginal-zone, 8 follicle-center lymphoma) and 7 (21%) had large cell PCBCL (3 follicle-center, 3 leg-type, 1 indeterminate). PET/CT detected skin lesions in 3 of 26 patients (12%) with small-cell PCBCL as compared to 6 of 7 patients with large-cell PCBLC (86%), a 7.4-fold detection risk (95% confidence interval, 2.4-22, P = 0.004). The PET-positive subgroup was characterized by larger lesion size (P < 0.001) and a higher Ki-67 proliferation index (P < 0.001)., Conclusions: The sensitivity of PET/CT for detecting cutaneous involvement of lymphomas is low for small-cell PCBCL but high for large-cell types, and thus may facilitate therapeutic strategies.
- Published
- 2019
34. IL-17A Inhibitor Switching - Efficacy of Ixekizumab Following Secukinumab Failure. A Single-center Experience.
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Sherman S, Solomon Cohen E, Amitay-Laish I, Hodak E, and Pavlovsky L
- Subjects
- Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized adverse effects, Biological Products adverse effects, Female, Humans, Interleukin-17 immunology, Male, Middle Aged, Psoriasis diagnosis, Psoriasis immunology, Retrospective Studies, Severity of Illness Index, Treatment Failure, Antibodies, Monoclonal, Humanized therapeutic use, Biological Products therapeutic use, Drug Substitution, Interleukin-17 antagonists & inhibitors, Psoriasis drug therapy
- Abstract
Interleukin-17A inhibitors are a promising alternative to tumor necrosis factor-α inhibitors for the treatment of psoriasis. In-class switch has been hardly investigated for interleukin-17A inhibitors. We report the experience (2017-2018) of a tertiary medical center with interleukin-17A-inhibitor switch in patients with moderate-to-severe psoriasis. Patient-, disease- and outcome-related data were retrospectively collected from the electronic files of 25 patients switched to ixekizumab following secukinumab failure. Mean ± standard deviation patient age was 56.7 ± 12.2 years. Mean baseline Psoriasis Area and Severity Index was 25. Secukinumab was discontinued due to primary failure in 7 patients and secondary failure in 18. Ixekizumab was administered for 7.3 ± 2.8 months; 22 patients were still on ixekizumab at the end of the study. Mean ± standard deviation Psoriasis Area and Severity Index reduction from baseline at study end was 75.5±20.0%. Patients with moderate-to-severe psoriasis seem to be amenable to treatment with ixekizumab following secukinumab failure. Further large multicenter studies are needed.
- Published
- 2019
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35. Retinoic acid receptor agonist as monotherapy for early-stage mycosis fungoides: does it work?
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Amitay-Laish I, Reiter O, Prag-Naveh H, Kershenovich R, and Hodak E
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Female, Humans, Male, Middle Aged, Retinoid X Receptors agonists, Retrospective Studies, Young Adult, Acitretin therapeutic use, Dermatologic Agents therapeutic use, Isotretinoin therapeutic use, Mycosis Fungoides drug therapy, Skin Neoplasms drug therapy
- Abstract
Background: Retinoids exert their biologic effects by binding to intracellular retinoic-acid receptors (RARs) and/or retinoid X receptors (RXRs). Early-stage mycosis fungoides (MF) has been effectively treated with bexarotene, an RXR-agonist, with overall response (OR) rates 54-67% and complete response (CR) rates 7-27%. Data on RAR-agonist monotherapy are limited., Objective: To analyze the effectiveness of RAR-agonist monotherapy for early-stage MF., Methods: Data on patients with early-stage MF treated with acitretin/isotretinoin monotherapy at a tertiary cutaneous lymphoma clinic in 2010-2017 were collected retrospectively from the medical files., Results: Thirty-five patients (26 males) of median age 50 years (range 8-83) with early-stage MF (IA 9, IB 26) underwent 37 treatment events: 25 acitretin and 12 isotretinoin at a median dosages of 0.3 mg/kg (range 0.2-0.9) and 0.2 mg/kg (range 0.1-0.7), respectively. Median time to maximal response was 6 months for both (range 1-10 for acitretin, 3-16 for isotretinoin); median treatment duration was 10 months (range 3-46) for acitretin, and 9 months (range 3-55) for isotretinoin. OR was 64% for acitretin and 80% for isotretinoin, and CR, 4% and 8%, respectively. Side-effect profiles were as previously reported for retinoids., Conclusions: Early-stage MF patients may benefit from low dose RAR-agonist monotherapy, although the CR rate is low.
- Published
- 2019
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36. Mycosis fungoides: A great imitator.
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Hodak E and Amitay-Laish I
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- Diagnosis, Differential, Female, Humans, Male, Mycosis Fungoides classification, Mycosis Fungoides etiology, Mycosis Fungoides diagnosis, Mycosis Fungoides pathology, Skin pathology
- Abstract
Mycosis fungoides (MF), the most common cutaneous T-cell lymphoma, typically presents in its early stage as inflammatory erythematous patches or plaques, with epidermotropism as the histopathologic hallmark of the disease. Over the past 30 years, numerous atypical types of MF, which deviate from the classic Alibert-Bazin presentation of the disease, have been described. These variants can simulate a wide variety of benign inflammatory skin disorders either clinically, both clinically and histopathologically, or mainly histopathologically. We have summarized the many faces of the disease, which set MF as a "great imitator," with special focus on the differential diagnosis and its benign mimickers., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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37. Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium.
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Quaglino P, Maule M, Prince HM, Porcu P, Horwitz S, Duvic M, Talpur R, Vermeer M, Bagot M, Guitart J, Papadavid E, Sanches JA, Hodak E, Sugaya M, Berti E, Ortiz-Romero P, Pimpinelli N, Servitje O, Pileri A, Zinzani PL, Estrach T, Knobler R, Stadler R, Fierro MT, Alberti Violetti S, Amitay-Laish I, Antoniou C, Astrua C, Chaganti S, Child F, Combalia A, Fabbro S, Fava P, Grandi V, Jonak C, Martinez-Escala E, Kheterpal M, Kim EJ, McCormack C, Miyagaki T, Miyashiro D, Morris S, Muniesa C, Nikolaou V, Ognibene G, Onida F, Osella-Abate S, Porkert S, Postigo-Llorente C, Ram-Wolff C, Ribero S, Rogers K, Sanlorenzo M, Stranzenbach R, Spaccarelli N, Stevens A, Zugna D, Rook AH, Geskin LJ, Willemze R, Whittaker S, Hoppe R, Scarisbrick J, and Kim Y
- Published
- 2019
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38. Treatment of Early Folliculotropic Mycosis Fungoides with Special Focus on Psoralen plus Ultraviolet A.
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Amitay-Laish I, Prag-Naveh H, Dalal A, Pavlovsky L, Feinmesser M, and Hodak E
- Subjects
- Adolescent, Adult, Aged, Female, Humans, Maintenance Chemotherapy, Male, Middle Aged, Mycosis Fungoides pathology, Neoplasm Staging, Remission Induction, Retrospective Studies, Skin Neoplasms pathology, Treatment Outcome, Young Adult, Mycosis Fungoides drug therapy, PUVA Therapy, Skin Neoplasms drug therapy
- Abstract
Data on the treatment of early folliculotropic mycosis fungoides, a recently defined clinicopathological subgroup of folliculotropic mycosis fungoides with an indolent course, is limited. Treatment outcomes were studied in a retrospective cohort of 47 adults with early folliculotropic mycosis fungoides, with a focus on psoralen plus ultraviolet A (PUVA) monotherapy, including dosimetric data, and the findings were compared with data for PUVA in 18 adults with early-classic mycosis fungoides. PUVA was given to 27 patients with early folliculotropic mycosis fungoides: 70% achieved complete response and 26% partial response. Significantly more treatments were needed to achieve complete response in stage IB compared with stage IA. There was no significant difference in the complete response rate from classic plaque-stage disease, although the early folliculotropic mycosis fungoides group required more treatments to achieve complete response, and a higher cumulative dose of UVA. Thus, PUVA is an effective treatment for early folliculotropic mycosis fungoides. Its complete response rate might be equal to early-classic mycosis fungoides; however, a longer induction phase is needed to achieve complete response.
- Published
- 2018
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39. Lack of detectable effect of narrow-band ultraviolet B on peripheral blood mononuclear cell cytokine expression in early-stage mycosis fungoides.
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Amitay-Laish I, Davidovici B, Moyal L, Gurevich M, Akerman L, and Hodak E
- Subjects
- Adult, Female, Humans, Male, Monokines blood, Mycosis Fungoides blood, Ultraviolet Rays, Ultraviolet Therapy
- Published
- 2018
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40. Pediatric mycosis fungoides: a study of the human leukocyte antigen system among Israeli Jewish patients.
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Reiter O, Ben Amitai D, Amitay-Laish I, Israeli M, Pavlovsky L, and Hodak E
- Subjects
- Adolescent, Adult, Age Factors, Alleles, Female, Fetal Blood, Gene Frequency, Genotyping Techniques, Healthy Volunteers, Humans, Israel, Male, Histocompatibility Antigens Class I genetics, Histocompatibility Antigens Class II genetics, Jews genetics, Mycosis Fungoides genetics, Skin Neoplasms genetics
- Abstract
Pediatric mycosis fungoides (MF) is a rare disease characterized by over-representation of atypical clinical variants, with a different prognosis from adult MF. Several human leukocyte antigen (HLA) alleles have been associated with MF in certain adult populations, including Israeli Jews. However, HLA data on pediatric MF as a group are lacking. To evaluate the possible association of the HLA system with pediatric MF, 59 Israeli Jewish patients diagnosed with MF at age ≤ 18 years underwent high- and intermediate-resolution genotyping for HLA class I (HLA-A*, HLA-B*) and class II (HLA-DRB1*, DQB1*) loci. The results were compared with data on 4169 umbilical cord blood units retrieved from a public cord blood bank in Jerusalem and samples from 252 healthy, unrelated Israeli Jewish volunteers. No statistically significant associations were found between pediatric MF and any of the alleles examined except HLA-B*73. However, given the extremely low frequency of B*73 in both the control group (0.1%) and the study group (2%), the biological significance of this finding is questionable. Further subgroup analyses by ethnicity (Ashkenazi and non-Ashkenazi) and clinicopathologic variant (follicular and non-follicular) yielded no significant between-group differences. These results suggest that the associations with the HLA system, reported previously in adult MF, do not hold true for pediatric MF. Thus, pediatric MF differs from its adult counterpart not only in clinical manifestations and course, but apparently also in the underlying immuno-pathogenetic mechanism.
- Published
- 2017
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41. Early clinical manifestations of Sézary syndrome: A multicenter retrospective cohort study.
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Mangold AR, Thompson AK, Davis MD, Saulite I, Cozzio A, Guenova E, Hodak E, Amitay-Laish I, Pujol RM, Pittelkow MR, and Gniadecki R
- Subjects
- Aged, Biopsy, Delayed Diagnosis, Dermatitis etiology, Female, Humans, Lymphadenopathy etiology, Male, Middle Aged, Prognosis, Receptors, Antigen, T-Cell genetics, Retrospective Studies, Sezary Syndrome complications, Skin pathology, Survival Rate, Dermatitis, Exfoliative etiology, Mycosis Fungoides etiology, Sezary Syndrome diagnosis, Sezary Syndrome pathology
- Abstract
Background: Classic Sézary syndrome (SS) is defined by erythroderma, generalized lymphadenopathy, and leukemic blood involvement. Clinical observations suggest that SS begins as a nonerythrodermic disease., Objective: To describe the early clinical characteristics of patients with SS., Methods: A retrospective, multicenter chart review was performed for 263 confirmed cases of SS diagnosed during 1976-2015., Results: Erythroderma was the earliest recorded skin sign of SS in only 25.5% of cases, although most patients (86.3%) eventually developed erythroderma. In patients without erythroderma during their initial visit, the first cutaneous signs of SS were nonspecific dermatitis (49%), atopic dermatitis-like eruption (4.9%), or patches and plaques of mycosis fungoides (10.6%). The mean diagnostic delay was 4.2 years overall, 2.2 years for cases involving erythroderma at the initial presentation, and 5.0 years for cases not involving erythroderma at the initial presentation., Limitations: This study is retrospective., Conclusion: Erythroderma is uncommon as an initial sign of SS. Early SS should be considered in cases of nonerythrodermic dermatitis that is refractory to conventional treatments. In these cases, examination of the blood by PCR for monoclonal T-cell receptor rearrangement and by flow cytometry to identify an expanded or aberrant T-cell population should be considered., (Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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42. Localized skin-limited blastic plasmacytoid dendritic cell neoplasm: A subset with possible durable remission without transplantation.
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Amitay-Laish I, Sundram U, Hoppe RT, Hodak E, Medeiros BC, and Kim YH
- Published
- 2017
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43. New insights into folliculotropic mycosis fungoides (FMF): A single-center experience.
- Author
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Hodak E, Amitay-Laish I, Atzmony L, Prag-Naveh H, Yanichkin N, Barzilai A, Kershenovich R, and Feinmesser M
- Subjects
- Adult, Aged, Disease Progression, Female, Follow-Up Studies, Humans, Male, Middle Aged, Mycosis Fungoides complications, Neoplasm Staging, Prognosis, Pruritus etiology, Retrospective Studies, Skin Neoplasms complications, Young Adult, Mycosis Fungoides pathology, Skin Neoplasms pathology
- Abstract
Background: It is generally accepted that folliculotropic mycosis fungoides (FMF) is usually typified by indurated plaques and tumors mainly on the head/neck and an aggressive course. However, its clinical manifestations have long been recognized to be quite variable, and some studies indicate a better prognosis for certain presentations., Objective: We sought to summarize our experience with the clinicopathological presentations of FMF and impact on prognosis., Methods: Data were collected retrospectively for adults with FMF followed up prospectively at a tertiary medical center in 1995 through 2014., Results: In all, 34 patients presented with follicle-based patch/flat plaques, keratosis pilaris-like lesions, and/or acneiform lesions, defined clinically as early stage (IA, IB), and 15 presented with follicle-based infiltrated plaques and/or tumors, defined as advanced stage (IIB). The head/neck was involved in all tumor-stage cases, whereas early-stage lesions involved mainly the trunk/limbs. The tumor stage was characterized by more pruritus, heavier perifollicular infiltrates, greater vertical depth, and more frequent presence of eosinophils. On multivariate analysis, infiltrate density was the only significant histopathological discriminator between the stages. Estimated 5-year survival was 0.94 in the early-stage group and 0.69 in the tumor-stage group., Limitations: Lack of long-term follow-up and relatively small sample are limitations., Conclusion: FMF presents with 2 distinct patterns of clinicopathologic features, early stage and advanced stage, each with different prognostic implications., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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44. Widespread morbilliform rash due to sorafenib or vemurafenib treatment for advanced cancer; experience of a tertiary dermato-oncology clinic.
- Author
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Ollech A, Stemmer SM, Merims S, Lotem M, Popovtzer A, Hendler D, Hodak E, Didkovsky E, and Amitay-Laish I
- Subjects
- Aged, Antineoplastic Agents administration & dosage, Drug Eruptions etiology, Female, Humans, Indoles administration & dosage, Male, Middle Aged, Niacinamide administration & dosage, Niacinamide adverse effects, Phenylurea Compounds administration & dosage, Sorafenib, Steroids therapeutic use, Sulfonamides administration & dosage, Vemurafenib, Antineoplastic Agents adverse effects, Exanthema chemically induced, Exanthema therapy, Indoles adverse effects, Neoplasms drug therapy, Niacinamide analogs & derivatives, Phenylurea Compounds adverse effects, Sulfonamides adverse effects
- Abstract
Background: In the literature, there are minimal data for the treatment of grade 2 or 3 morbilliform/atypical target lesion rashes secondary to sorafenib or vemurafenib given for patients with advanced stage cancer. This poses a dilemma for clinicians, particularly in patients with advanced neoplastic disease for whom other optional treatments are limited., Methods: The cohort included data on all patients attending the dermato-oncological clinic at a tertiary medical center that presented in 2011-2014 with a widespread rash following treatment with sorafenib or vemurafenib. All patients were prospectively followed., Results: Eight patients met the study criteria. Five, under sorafenib, aged 50-65 years, presented with an extensive grade 2 (involving 20-30% of the body surface area, two patients) or grade 3 (three patients) morbilliform rash, 5-10 days after onset of the drug. Two had atypical target lesions. The dosage was temporarily reduced in only two patients, and oral steroids were added in four. Under vemurafenib, three patients presented with an extensive grade 3 morbilliform rash 5-10 days after onset of treatment. Two had atypical target lesions. The dose was temporarily reduced in one, and another patient stopped the drug at her own initiative; both also received steroids. The rash subsided after 2-3 weeks in all eight patients, allowing continuation of the treatment at the regular dose., Conclusion: Our cohort suggests that not all cases of widespread morbilliform rash or atypical erythema multiforme, which occur under treatment with sorafenib or vemurafenib, given for advanced cancer, require discontinuation of therapy., (© 2016 The International Society of Dermatology.)
- Published
- 2016
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45. The Therapeutic Potential of AN-7, a Novel Histone Deacetylase Inhibitor, for Treatment of Mycosis Fungoides/Sezary Syndrome Alone or with Doxorubicin.
- Author
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Moyal L, Feldbaum N, Goldfeiz N, Rephaeli A, Nudelman A, Weitman M, Tarasenko N, Gorovitz B, Maron L, Yehezkel S, Amitay-Laish I, Lubin I, and Hodak E
- Subjects
- Acetylation drug effects, Apoptosis drug effects, Butyrates, Cell Line, Cell Survival drug effects, Down-Regulation drug effects, Doxorubicin pharmacology, Drug Therapy, Combination, Histone Deacetylase Inhibitors pharmacology, Histone Deacetylases metabolism, Histones metabolism, Humans, Hydroxamic Acids pharmacology, Hydroxamic Acids therapeutic use, Lymphocytes metabolism, Organophosphates pharmacology, Organophosphorus Compounds, Phosphates pharmacology, Vorinostat, Doxorubicin therapeutic use, Histone Deacetylase Inhibitors therapeutic use, Mycosis Fungoides drug therapy, Organophosphates therapeutic use, Phosphates therapeutic use, Sezary Syndrome drug therapy
- Abstract
The 2 histone deacetylase inhibitors (HDACIs) approved for the treatment of cutaneous T-cell lymphoma (CTCL) including mycosis fungoides/sezary syndrome (MF/SS), suberoylanilide hydroxamic acid (SAHA) and romidepsin, are associated with low rates of overall response and high rates of adverse effects. Data regarding combination treatments with HDACIs is sparse. Butyroyloxymethyl diethylphosphate (AN-7) is a novel HDACI, which was found to have selective anticancer activity in several cell lines and animal models. The aim of this study was to compare the anticancer effects of AN-7 and SAHA, either alone or combined with doxorubicin, on MF/SS cell lines and peripheral blood lymphocytes (PBL) from patients with Sezary syndrome (SPBL). MyLa cells, Hut78 cells, SPBL, and PBL from healthy normal individuals (NPBL) were exposed to the test drugs, and the findings were analyzed by a viability assay, an apoptosis assay, and Western blot. AN-7 was more selectively toxic to MyLa cells, Hut78 cells, and SPBL (relative to NPBL) than SAHA and also acted more rapidly. Both drugs induced apoptosis in MF/SS cell lines, SAHA had a greater effect on MyLa cell line, while AN-7 induced greater apoptosis in SPBL; both caused an accumulation of acetylated histone H3, but AN-7 was associated with earlier kinetics; and both caused a downregulation of the HDAC1 protein in MF/SS cell lines. AN-7 acted synergistically with doxorubicin in both MF/SS cell lines and SPBL, and antagonistically with doxorubicin in NPBL. By contrast, SAHA acted antagonistically with doxorubicin on MF/SS cell lines, SPBL, and NPBL, leaving <50% viable cells. In conclusion, AN-7 holds promise as a therapeutic agent in MF/SS and has several advantages over SAHA. Our data provide a rationale for combining AN-7, but not SAHA, with doxorubicin to induce the cell death in MF/SS.
- Published
- 2016
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46. Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model.
- Author
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Scarisbrick JJ, Prince HM, Vermeer MH, Quaglino P, Horwitz S, Porcu P, Stadler R, Wood GS, Beylot-Barry M, Pham-Ledard A, Foss F, Girardi M, Bagot M, Michel L, Battistella M, Guitart J, Kuzel TM, Martinez-Escala ME, Estrach T, Papadavid E, Antoniou C, Rigopoulos D, Nikolaou V, Sugaya M, Miyagaki T, Gniadecki R, Sanches JA, Cury-Martins J, Miyashiro D, Servitje O, Muniesa C, Berti E, Onida F, Corti L, Hodak E, Amitay-Laish I, Ortiz-Romero PL, Rodríguez-Peralto JL, Knobler R, Porkert S, Bauer W, Pimpinelli N, Grandi V, Cowan R, Rook A, Kim E, Pileri A, Patrizi A, Pujol RM, Wong H, Tyler K, Stranzenbach R, Querfeld C, Fava P, Maule M, Willemze R, Evison F, Morris S, Twigger R, Talpur R, Kim J, Ognibene G, Li S, Tavallaee M, Hoppe RT, Duvic M, Whittaker SJ, and Kim YH
- Subjects
- Adult, Age Factors, Aged, Cell Transformation, Neoplastic metabolism, Cell Transformation, Neoplastic pathology, Female, Humans, Kaplan-Meier Estimate, L-Lactate Dehydrogenase blood, L-Lactate Dehydrogenase metabolism, Male, Middle Aged, Mycosis Fungoides metabolism, Neoplasm Staging, Predictive Value of Tests, Prognosis, Risk Factors, Sezary Syndrome metabolism, Skin enzymology, Skin Neoplasms metabolism, Survival Rate, Models, Statistical, Mycosis Fungoides mortality, Mycosis Fungoides pathology, Sezary Syndrome mortality, Sezary Syndrome pathology, Skin Neoplasms mortality, Skin Neoplasms pathology
- Abstract
Purpose: Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers., Patients and Methods: Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS)., Results: Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%)., Conclusion: To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and identifies markers with independent prognostic value, which, used together in a prognostic index, may be useful to stratify advanced-stage patients., (© 2015 by American Society of Clinical Oncology.)
- Published
- 2015
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47. Response to: "Tumor stage mycosis fungoides in nonblood-related family members".
- Author
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Hodak E and Amitay-Laish I
- Subjects
- Female, Humans, Male, Mycosis Fungoides etiology, Mycosis Fungoides pathology
- Published
- 2014
- Full Text
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48. Juvenile mycosis fungoides: cutaneous T-cell lymphoma with frequent follicular involvement.
- Author
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Hodak E, Amitay-Laish I, Feinmesser M, Davidovici B, David M, Zvulunov A, Pavlotsky F, Yaniv I, Avrahami G, and Ben-Amitai D
- Subjects
- Adolescent, Age Factors, Biopsy, Needle, Child, Child, Preschool, Cohort Studies, Female, Humans, Immunohistochemistry, Incidence, Israel, Lymphoma, T-Cell, Cutaneous diagnosis, Lymphoma, T-Cell, Cutaneous epidemiology, Lymphoma, T-Cell, Cutaneous radiotherapy, Male, Mycosis Fungoides diagnosis, Mycosis Fungoides epidemiology, Mycosis Fungoides radiotherapy, Neoplasm Invasiveness pathology, Neoplasm Staging, Prognosis, Retrospective Studies, Risk Assessment, Sex Factors, Skin Neoplasms diagnosis, Skin Neoplasms epidemiology, Skin Neoplasms radiotherapy, Treatment Outcome, Ultraviolet Therapy methods, Lymphoma, T-Cell, Cutaneous pathology, Mycosis Fungoides pathology, Skin Neoplasms pathology
- Abstract
Background: The literature on mycosis fungoides (MF) in children/adolescents is sparse., Objective: We sought to evaluate the characteristics of juvenile MF in a large cohort., Methods: Data were collected on all patients with MF, aged 18 years or younger at the time of clinicopathologic diagnosis, who attended the Rabin Medical Center Dermatology Department, Petach Tikva, Israel, between 1994 and 2012 and were followed up prospectively., Results: There were 50 patients (30 male; mean age 11.4 years at diagnosis); 18 (36%) had Fitzpatrick skin type IV or higher. All were given a diagnosis of early-stage disease (IA-IIA) except 1 (tumor stage, IIB). Eight had classic MF lesions only and 42 had other variants, alone or in combination; these were mainly hypopigmented MF (n = 29) and cases with subtle but clear clinicopathologic features of folliculotropic MF (FMF) (n = 18). Among the various skin-targeted therapies, psoralen plus ultraviolet A (systemic/bath) proved beneficial for FMF. During a follow-up period of 0.25 to 15 years (mean 4.5), 2 patients progressed from stage IA to IB or IIA., Limitations: Relatively short follow-up is a limitation., Conclusions: This case series shows that FMF is not uncommon in children and adolescents. It is characterized by more superficial clinical features and less heavy perifollicular lymphocytic infiltrates than adult FMF, and responds well to psoralen plus ultraviolet A. The prognosis of childhood FMF remains unclear., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
49. Rash with the multitargeted kinase inhibitors nilotinib and dasatinib: meta-analysis and clinical characterization.
- Author
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Drucker AM, Wu S, Busam KJ, Berman E, Amitay-Laish I, and Lacouture ME
- Subjects
- Dasatinib, Drug Eruptions epidemiology, Exanthema epidemiology, Guideline Adherence, Humans, Incidence, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive epidemiology, Protein Kinase Inhibitors therapeutic use, Pyrimidines therapeutic use, Quality of Life, Thiazoles therapeutic use, Drug Eruptions prevention & control, Exanthema chemically induced, Exanthema prevention & control, Protein Kinase Inhibitors adverse effects, Pyrimidines adverse effects, Thiazoles adverse effects
- Abstract
Objectives: Nilotinib and dasatinib are second-generation tyrosine kinase inhibitors approved for the treatment of chronic myeloid leukemia (CML). In clinical trials, they have both been reported to cause rash in a significant number of patients, but its incidence varies significantly and has not been characterized clinically or histologically. The aim of this study was to determine the incidence of rash with nilotinib and dasatinib, and to provide a clinical and histopathological description of the rash., Methods: We conducted a meta-analysis of clinical trials evaluating nilotinib and dasatinib to determine and compare the incidence of rash with these medications. Additionally, we performed a retrospective chart review to analyze the clinical presentation and histology of patients presenting with rash., Results: The incidence of all-grade (grade 1-4) rash with nilotinib was 34.3% (95% CI, 27.9-41.3), higher (P = 0.017) than with dasatinib (23.3%; 95% CI, 18.8-28.6). Similarly, the incidence of high-grade rash with nilotinib (2.6%; 95% CI, 2.1-3.4) was higher (P = 0.002) than with dasatinib (1.1%; 95% CI, 0.8-1.6). The clinical presentation often consisted of a pruritic, perifollicular hyperkeratotic, occasionally erythematous papular rash affecting most areas of the body, depending on the severity., Conclusions: Both nilotinib and dasatinib are associated with rash in a significant number of patients. Further studies to prevent and treat rash with nilotinib and dasatinib are required to improve patient quality of life, adherence with therapy and oncologic outcome., (© 2012 John Wiley & Sons A/S.)
- Published
- 2013
- Full Text
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50. Human herpesvirus 8 is not detectable in lesions of large plaque parapsoriasis, and in early-stage sporadic, familial, and juvenile cases of mycosis fungoides.
- Author
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Amitay-Laish I, Sarid R, Ben-Amitai D, Kalt I, Masa SR, David M, Feinmesser M, and Hodak E
- Subjects
- Adult, Child, Computers, Handheld, DNA, Viral analysis, Humans, Mycosis Fungoides genetics, Herpesvirus 8, Human isolation & purification, Mycosis Fungoides virology, Parapsoriasis virology, Skin virology
- Abstract
Background: Human herpesvirus (HHV) 8, an essential etiologic agent of Kaposi sarcoma, is also associated with several lymphoproliferative disorders. The involvement of HHV 8 in mycosis fungoides (MF) and large plaque parapsoriasis (LPP) is controversial, with contradictory reports from various countries worldwide., Objective: We sought to investigate the presence of the HHV 8 genome in skin lesions of LPP and early-stage sporadic, familial, and juvenile MF in patients in Israel., Methods: Archival paraffin-embedded and frozen samples from skin biopsies of untreated patients with LPP and early-stage MF performed in 1990 through 2006 were randomly collected from the department of dermatology of a tertiary medical center in central Israel. DNA was extracted, and a TaqMan-based real-time polymerase chain reaction assay specific for the K6 gene region was used to detect the HHV 8 genome., Results: A total of 46 biopsies were sampled from 11 patients with LPP and 35 with early-stage MF (17 adults with sporadic MF, 10 children, and 8 patients with familial MF). In all, 44 samples were negative for HHV 8 DNA; two samples from adults with sporadic MF were positive., Limitations: The presence of HHV 8 antibodies or virus sequences was not assessed in peripheral blood., Conclusion: The results of this study, conducted in a region relatively endemic for HHV 8, support most earlier studies showing a lack of association of HHV 8 infection with LPP and sporadic adult-type MF. To our knowledge, the lack of association of HHV 8 infection with juvenile and familial MF has not been previously reported., (Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
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