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Cutaneous T-cell Lymphomas
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Disease Stage |
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Stage |
T N M |
Description |
IA |
T1 N0 M0 |
Patches, plaques over < 10% of the body surface area |
IB |
T2 N0 M0 |
Patches, plaques over > 10% of body surface area |
IIA |
T1-2 |
Patches, plaques Clinically abnormal, histologically uninvolved lymph nodes |
IIB |
T3 |
Cutaneous tumors Clinically normal or abnormal lymph nodes, histologically uninvolved |
III |
T4 |
Generalized erythroderma Clinically normal or abnormal lymph nodes, histologically uninvolved |
IVA |
T1-4 |
Patches, plaques, + tumors, + generalized erythroderma Clinically normal or abnormal lymph nodes, histologically involved |
IVB |
T1-4 |
Patches, plaques, + tumors, + generalized erythroderma Clinically normal or abnormal lymph nodes, histologically involved or uninvolved Visceral (organ) involvement |
Adapted from AJCC Cancer Staging Manual 2002:393 |
5 and 10 Year Survival with Mycosis Fungoides/Sezary Syndrome
Rate (%) of:
IA
IB
IIA
IIB
III
IVA
IVB
5-yr disease-specific survival*
100%
96
68
80
-
40
0
10-yr disease-specific survival
97-98
83
68
42
-
20
0
5-yr survival
96-100
73 - 86
49 - 73
40 - 65
40 - 57
15 - 40
0 - 15
10-yr survival
84 - 100
58-67
45-49
20-39
20-40
5-20
0-5
Whittaker, S.J., Foss, F.M., Cancer Treat Rev 2007 33:146
Disease-specific survival rate "The percentage of people in a study or treatment group who have not died from a specific disease in a defined period of time. The time period usually begins at the time of diagnosis or at the start of treatment and ends at the time of death. Patients who died from causes other than the disease being studied are not counted in this measurement" (NCI)Treatments: Early stage treatments such as topical therapies: steroid creams, chemotherapy applied to the skin, phototherapy, photopheresis or electron beam radiation may be used.
MF may lead to extracutaneous (beyond skin) involvement, including blood, lymph nodes, and internal organs of the body (viscera), which can be treated with systemic therapies - chemotherapy
Infection is an ongoing complication.
Recently approved systemic therapies:
Bexarotene (1999 for cutaneous CTCL)
Bexarotene gel is a retinoid X receptor agonist and is approved for early-stage mycosis fungoides.90 In clinical trials, it has been shown to have an overall response rate (ORR) of 54% and a complete response rate of 10% in patients with stages IA–IIA mycosis fungoides. It commonly causes skin irritation. Source: http://1.usa.gov/1mSpyx3
Denileukin diftitox (2008 for cd25+ CTCL),
Vorinostat (2006 for cutaneous CTCL),
A leukemic variant of CTCL characterized by
Blood involvement (Leukemic) with abnormal circulating T cells known as Sézary cells. |
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Pruritic (severe itching) erythroderma - inflammatory skin disease with erythema and scaling that affects nearly the entire cutaneous surface) |
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Enlarge lymph nodes |
Management of cutaneous T cell lymphoma:
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Journal of Hematology & Oncology 2012
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More on CTCL: Medscape | archderm.ama-assn.org | clfoundation.org |
ASH 2017: Targeted Antibody Mogamulizumab Superior to Vorinostat for Previously Treated CTCL in Phase III Trial - The ASCO Post http://bit.ly/2mv3NXc |
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2015: Cutaneous T-cell lymphoma: 2016 update on diagnosis, risk-stratification, and management. - PubMed - NCBI http://1.usa.gov/1OzVwZt |
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* Youtube 2013:
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Ontak (Denileukin Diftitox) Clin Lymphoma Myeloma Leuk. 2013 |
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The ASCO Post, 2013: FDA Approves Mechlorethamine Gel for Cutaneous T-Cell Lymphoma http://bit.ly/18Ultxa
This gel is the first and only FDA-approved topical formulation of mechlorethamine, which is commonly known as nitrogen mustard. The gel is applied topically once a day and dries on the skin. Mechlorethamine was approved previously for intravenous treatment of mycosis fungoides, the most common type of CTCL. Topical mechlorethamine preparations are currently recommended for the treatment of early-stage CTCL. Prior to approval of the gel, there were no FDA-approved topical mechlorethamine products; only non-standardized, pharmacy-compounded petroleum ointment or aqueous-based topical preparations were available. |
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News Medical: FDA grants Fast Track designation to Elorac's
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Journal of Hematology & Oncology 2012
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Oncology Times: Photopheresis in the treatment of cutaneous T-cell lymphoma: current status
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Dr. John Zic of Vanderbilt University discusses controversies in cutaneous T cell lymphomas, particularly the difficulties in diagnosis. Diagnostic Challenges in Cutaneous T-Cell Lymphoma |
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Cutaneous T Cell - Brit J Dermatology:
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Clinical efficacy of zanolimumab (HuMax-CD4): two phase 2 studies in refractory cutaneous T-cell lymphoma http://bloodjournal.hematologylibrary.org/content/109/11/4655.long |
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Phase 2 trial of oral vorinostat (SAHA) for refractory cutaneous T-cell lymphoma (CTCL) ncbi.nlm.nih.gov |
Clinical efficacy of zanolimumab (HuMax-CD4): two phase 2 studies in refractory cutaneous T-cell lymphoma http://bloodjournal.hematologylibrary.org/content/109/11/4655.long |
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Efficacy and tolerability of currently available therapies for the mycosis fungoides and Sezary syndrome variants of cutaneous T-cell lymphoma. Whittaker SJ, Foss FM. Cancer Treat Rev. 2007 Apr;33(2):146-60. Epub 2007 Feb 1. Review. PMID: 17275192 |
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Pegylated liposomal doxorubicin effective in poor prognosis CTCL medwire-news
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Phase 2 Data for Romidepsin Showing Durable Response in Refractory CTCL businesswire.com
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ASH: Forodesine HCl active single oral agent for advanced refractory CTCL abstracts2view.com | ClinicalTrials.gov
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Treatment of mycosis fungoides using a 308-nm excimer laser: two case studies.
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506U78 (Nelarabine) Results of a phase II study of 506U78 in cutaneous T-cell lymphoma and peripheral T-cell lymphoma: CALGB 59901. Leuk Lymphoma. 2007 Jan;48(1):97-103. PMID: 17325852 | ClinicalTrials.gov |
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Anti-cd2 (Siplizumab) antibody (investigational) ash05 | ClinicalTrials.gov
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Anti-cd30 (SGN-30) antibodies (investigational) PubMed articles | ClinicalTrials.gov
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Bexarotene PubMed articles | ClinicalTrials.gov
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Bexarotene with ONTAK PubMed articles | ClinicalTrials.gov |
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Extracorporeal photopheresis PubMed articles | ClinicalTrials.gov
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HDAC inhibitor: Depsipeptide PubMed articles | ClinicalTrials.gov
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Interleukin 12 Active in Mycosis Fungoides (a T-cell lymphoma) cancerconsultants.com
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Immune modulation PubMed articles | ClinicalTrials.gov
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Immune therapy PubMed articles | ClinicalTrials.gov
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Lenalidomide / Revlimid (investigational) PubMed articles | ClinicalTrials.gov
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ONTAK (denileukin diftitox) PubMed articles | ClinicalTrials.gov |
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Transimmunization (immune therapy) Clinical trial: med.yale.edu
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2002
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2006
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Phase II Trial of Oral Vorinostat (Suberoylanilide Hydroxamic Acid, SAHA) for Refractory Cutaneous T-cell Lymphoma (CTCL). Blood. 2006 Sep 7; PMID: 16960145 | Related articles
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International multicenter phase II study of the HDAC inhibitor (HDACi) depsipeptide (FK228) in cutaneous T-cell lymphoma (CTCL): Interim report. ASCO 2006
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About PUVA - Photopheresis is a process where your white blood cells are separated from the rest of your blood. The white blood cells are exposed the methoxsalen and UV light and then reinfused back into you. rmhonline.com |
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T-Cell Lymphoma Successfully Treated with Psoralen Plus UV-A Therapy cancerconsultants.comAccording to a recent article in the Archives of Dermatology, Psoralen plus UV-A (PUVA) is an effective treatment for patients with mycosis fungoides (MF), inducing long-term remissions and in some cases, disease cure. |
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Immunophenotypic and molecular features, clinical outcomes, treatments, and prognostic factors associated with subcutaneous panniculitis-like T-cell lymphoma: a systematic analysis of 156 patients reported in the literature. Cancer. 2004 Sep 15;101(6):1404-13. PMID: 15368328 |
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HuMax-CD4 Phase II cutaneous T-cell lymphoma (CTCL) studies - 55% of Higher Dose Patients Achieve a Clinical Response in Primary Indication prnewswire Apr 2004 |
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Multicenter study of pegylated liposomal doxorubicin in patients with cutaneous T-cell lymphoma. Cancer. 2003 Sep 1;98(5):993-1001. PMID: 12942567 |
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A complete and durable response to denileukin diftitox in a patient with mycosis fungoides. J Am Acad Dermatol. 2003 Feb;48(2):275-6. PMID: 12582402 PubMed |
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Enhanced expression of T-cell activation and natural killer cell antigens indicates systemic anti-tumor response in early primary cutaneous T-cell lymphoma. J Invest Dermatol. 1997 May;108(5):743-7. PMID: 9129226 PubMed |
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EPOCH for refractory T-cell NHL Chemotherapy with etoposide, vincristine, doxorubicin, bolus cyclophosphamide, and oral prednisone in patients with refractory cutaneous T-cell lymphoma. Cancer. 1999 Oct 1;86(7):1368-76. PMID: 10506727 PubMed |
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Inhibitor of histone deacetylation, depsipeptide (FR901228), in the treatment of peripheral and cutaneous T-cell lymphoma: a case report. Blood. 2001 Nov 1;98(9):2865-8. PMID: 11675364 PubMed |
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Phase II trial of interferon-alpha-2a plus psolaren with ultraviolet light A in patients with cutaneous T-cell lymphoma. Cancer 2002; 95: 569-75. PubMed |
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Treatment of relapsing or recalcitrant cutaneous T-cell lymphoma with pegylated liposomal doxorubicin. J Am Acad Dermatol. 2000 Jan;42(1 Pt 1):40-6. PMID: 10607318 PubMed |
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Treatment of cutaneous T cell lymphoma: current status and future directions.
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Treatment of advanced mycosis fungoides by allogeneic stem-cell transplantation with a nonmyeloablative regimen. Bone Marrow Transplant. 2003 Apr;31(8):663-6. PMID: 12692606 PubMed |
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Treatment of cutaneous T cell lymphoma: current status and future directions. Am J Clin Dermatol. 2002;3(3):193-215. Review. PMID: 11978140 PubMed |
Under construction
Subcutaneous panniculitis-like (WHO and EORTC)
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Anaplastic large cell lymphoma (WHO) - PC CD30+ lymphoproliferative disorders, LyP/PCALCL
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Primary cutaneous peripheral T-cell lymphoma, unspecified (WHO)
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Primary Cutaneous Anaplastic Large Cell Lymphoma
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Extranodal NK/T-cell (CD56+) lymphoma, nasal type (WHO) / CD30- large cell lymphomas (EORTC)
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lymphomatoid granulomatosis |
About Medscape
Granulomatous slack skin disease | Adult T-cell leukemia/lymphoma | Pagetoid Reticulosis
Source: clfoundation.org
Trials for Untreated CTCL | Relapsed CTCL |
Tumor Burden Index in Cutaneous T-Cell Lymphoma Medal.org
Primary tumor (T)
T1: Eczematous patches, papules, or limited plaques covering less than 10% of the skin surface
T2: Erythematous patches, papules, or generalized plaques covering 10% or more of the skin surface
T3: Tumors, one or more
T4: Generalized erythroderma
When characteristics of more than one T exist,
both are recorded and the highest is used for staging, for example, T3(2).
Nodal involvement (N):
N0: No clinically abnormal peripheral lymph nodes, pathology negative for CTCL
N1: Clinically abnormal peripheral lymph nodes, pathology negative for CTCL
N2: No clinically abnormal peripheral lymph nodes, pathology positive for CTCL
N3: Clinically abnormal peripheral lymph nodes, pathology positive for CTCL
Distant metastasis (M)
M0: No involvement of visceral organs
M1: Visceral involvement (must have confirmation of pathology; organ involved should be specified)
Other Staging Terminology:
Early stage (T1 and T2)
IA : < 10% patch/plaque |
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IB: > 10% BSA patch/plaque |
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IIA: palpable adenopathy |
Intermediate stage
IIB: Cutaneous tumors (T3) |
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III: Erythroderma (T4) |
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IVA: Node biopsy positive |
Advanced state
Visceral involvement - "referring to the viscera, the internal organs of the body, specifically those within the chest (as the heart or lungs) or abdomen (as the liver, pancreas or intestines)." http://www.medterms.com |
Resources on Staging: http://www.meds.com/pdq/tcell_pro.html#3
About cutaneous lymphomas
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Lesional skin only
High potency topical steriods |
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Bexaratene gel |
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Other: Excision; Imiquimod; Photdynamic; UVB laser |
Lesional skin only
UVB |
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Topical HN2 or BCNU |
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Photochemotherapy |
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Radiotherapy |
Protocols for Refractory Disease PAL |
* Youtube 2013:
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Clinical abstracts CTCLconsult.com |
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Lymphoma of the Skin (Nov_28_02)
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Photopheresis Followed by Immunotherapy Improves Responses in Cutaneous T-Cell Lymphoma www.ufscc.ufl.edu |
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About Photopheresis PAL |
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T-Cell Lymphoma Presenting as Benign Dermatoses - includes images aafp.org |
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PDQ -- for Health Professionals NIH |
Diagnosis | Review | Therapies | Prognosis |
ClinicalTrials.gov studies for T-cell lymphomas |