Oncology Times: Photopheresis in the treatment of cutaneous T-cell lymphoma: current status

CTCL - Extracorporeal photopheresis (ECP), an immunomodulating procedure involving treatment of blood with a photoactive agent, was given regulatory approval by FDA as a medical device for the treatment of cutaneous T-cell lymphoma (CTCL) in 1988 [1]. It is one of many treatment options for CTCL.

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

Cutaneous T Cell - Brit J Dermatology:
Low-Dose Total Skin Electron Beam Therapy as a Debulking Agent:
An open-label prospective phase II study

Cutaneous T-cell lymphoma Clinical Trial Search http://bit.ly/eHWku2

Cutaneous T-cell Lymphomas (LLS) PDF

Cutaneous T-cell lymphoma Clinical Trial Search http://bit.ly/eHWku2

Review of the Treatment of Mycosis Fungoides and Sezary Syndrome: 
A Stage-Based Approach cutaneouslymphoma.stanford.edu  .pdf 

About MF rediseases.about.com

About Sézary syndrome Medscape 

Medscape  | archderm.ama-assn.org | clfoundation.org 

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

Phase 2 trial of oral vorinostat  (SAHA) for refractory cutaneous T-cell lymphoma (CTCL) ncbi.nlm.nih.gov

lymphomatoid granulomatosis 

All studies | Newly diagnosed or untreated  | Recurrent 

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 

About cutaneous lymphomas 

	eMedicine
	dermnetnz.org
	clfoundation.org
	NCI PDQ
	Dermatology Channel
	Review Article
	Resources on Staging: http://www.meds.com/pdq/tcell_pro.html#3
	Cutaneous T cell lymphoma Neeraj Srivastava MD, Nitin Mishra MBBS, Sanjay Singh MD DNB PhD Dermatology Online Journal 14 (8): 16  dermatology.cdlib.org  Excellent overview but the graphic image of the condition might be disturbing to some ... which may not be typical.
	Cutaneous T-cell lymphoma dermnetnz.org

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Protocols for Refractory Disease  PAL

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

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

Pegylated liposomal doxorubicin effective in poor prognosis CTCL medwire-news

Of the 10 patients with Sézary syndrome, six (60%) patients achieved an objective response at the end of treatment, including one complete response and five partial responses. Five (50%) of 10 patients with transformed CTCL achieved an objective response, including one patient who achieved a complete response and was still disease-free after 3 years.

Phase 2 Data for Romidepsin Showing Durable Response in Refractory CTCL businesswire.com 

"Romidepsin is a novel, cyclic peptide, pan-HDAC inhibitor under investigation for hematologic malignancies"

ASH: Forodesine HCl active single oral agent for advanced refractory CTCL  abstracts2view.com  | ClinicalTrials.gov

Forodesine is a rationally designed, potent inhibitor of purine nucleoside phosphorylase (PNP) that leads to intracellular accumulation of dGTP and then apoptosis. ... Conclusion: Oral forodesine demonstrates clinical activity in subjects with refractory CTCL, including those with SS, with minimal toxicity to date. 

Treatment of mycosis fungoides using a 308-nm excimer laser: two case studies.
Dermatol Online J. 2006 Dec 10;12(7):11. PMID: 17459297 

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

Anti-cd2 (Siplizumab) antibody (investigational)  ash05 | ClinicalTrials.gov

Siplizumab is a humanized IgG1κ class monoclonal antibody that binds to the CD2 receptor on 
human T- and NK-cells

Anti-cd30 (SGN-30) antibodies (investigational)  PubMed articles | ClinicalTrials.gov  

CD30 is a promising target for antibody-based immunotherapy of Hodgkin lymphoma (HL) and anaplastic large cell lymphoma.   PMID: 12881320 

Bexarotene  PubMed articles | ClinicalTrials.gov  
 
( beks-AIR-oh-teen) a retinoids (RET-i-noyds), applied to the skin Acts by interfering with the growth of cells of the tumor. It may be used after other drugs have been tried, and the tumor is still a problem. - MedlinePlus

Dose may be limited by cholesterol/TG elevations. Pretreatment with anti-lipid agents may be needed

Bexarotene with ONTAK  PubMed articles | ClinicalTrials.gov  

Extracorporeal photopheresis  PubMed articles | ClinicalTrials.gov
Is thought to induce antigen processing cell activation and apoptosis of CTCL cells

HDAC inhibitor: Depsipeptide  PubMed articles | ClinicalTrials.gov 

"Depsipeptide, FR901228, has demonstrated potent in vitro and in vivo cytotoxic activity against murine and human tumor cell lines. In the laboratory, it has been shown to be a histone deacetylase (HDAC) inhibitor. In a phase I trial of depsipeptide conducted at the National Cancer Institute, 3 patients with cutaneous T-cell lymphoma had a partial response, and 1 patient with peripheral T-cell lymphoma, unspecified, had a complete response. Sezary cells isolated from patients after treatment had increased histone acetylation. These results suggest that inhibition of HDAC is a novel and potentially effective therapy for patients with T-cell lymphoma."  PMID: 11675364 

Interleukin 12 Active in Mycosis Fungoides (a T-cell lymphoma)  cancerconsultants.com 

The current study involved 23 patients with mycosis fungoides, all of whom had received more than three prior therapies. These authors reported that 10 patients achieved a partial response (PR), 30% had minor responses and 22% had stable disease.

Immune modulation  PubMed articles | ClinicalTrials.gov
 
Immune therapy and immune modulation is likely most appropriate as an early treatment; 
not in advanced disease

Immune therapy  PubMed articles | ClinicalTrials.gov 
 
Improves durability of response in responders to combination therapy.

Lenalidomide / Revlimid  (investigational)  PubMed articles | ClinicalTrials.gov
 
A potent immune modulating agent. 

ONTAK (denileukin diftitox)  PubMed articles | ClinicalTrials.gov

Transimmunization (immune therapy)  Clinical trial: med.yale.edu 

"Transimmunization was developed after years of laboratory research advanced the understanding of the underlying principles of ECP (Extracorporeal, photochemotherapy, or photopheresis). 

The scientific basis of ECP is the ability to stimulate the development of powerful stimulators of the immune system called dendritic cells. Transimmunization is a more efficient means by which to bring these dendritic cells in contact with target cancer cells, before they are returned to the body to stimulate an anti-tumor immune response."

Clinical abstracts  CTCLconsult.com

Lymphoma of the Skin (Nov_28_02) 
 
Joseph M. Connors, Eric D. Hsi and Francine M. Foss Abstract  asheducationbook.org
Scroll down to Section III for Cutaneous T-Cell Lymphoma

Photopheresis Followed by Immunotherapy Improves Responses in Cutaneous T-Cell Lymphoma www.ufscc.ufl.edu 

About Photopheresis  PAL

T-Cell Lymphoma Presenting as Benign Dermatoses - includes images  aafp.org

PDQ -- for Health Professionals NIH

 Diagnosis | Review | Therapies | Prognosis

ClinicalTrials.gov studies for T-cell lymphomas

Assessment of tumor burden and treatment response by 18F-fluorodeoxyglucose injection and positron emission tomography in patients with cutaneous T- and B-cell lymphomas. J Am Acad Dermatol. 2002 Oct;47(4):623-8. PMID: 12271315

Treatment of mycosis fungoides using a 308-nm excimer laser: two case studies.
Dermatol Online J. 2006 Dec 10;12(7):11. PMID: 17459297 

Our findings confirm previous observations that the 308-nm excimer laser is a safe, effective, and well-tolerated therapy for early stage MF.

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 

Eight (of 31) patients achieved a PR, including 7 with advanced disease and 4 with Sezary syndrome. The median Time to Response, Duration of Response, and Time to Progression for responders were 11.9, 15.1, and 30.2 weeks, respectively. Fourteen of 31 evaluable patients had pruritus relief. The most common drug-related AE were fatigue, thrombocytopenia, diarrhea, and nausea.

International multicenter phase II study of the HDAC inhibitor (HDACi) depsipeptide (FK228) in cutaneous T-cell lymphoma (CTCL): Interim report.  ASCO 2006 

Conclusions: The previously reported efficacy of depsipeptide in CTCL has also been seen in the present study. Duration of response is encouraging. Toxicity is manageable and the study continues to accrue.

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 

T-Cell Lymphoma Successfully Treated with Psoralen Plus UV-A Therapy  cancerconsultants.com

According 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.

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 

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

Multicenter study of pegylated liposomal doxorubicin in patients with cutaneous T-cell lymphoma. Cancer. 2003 Sep 1;98(5):993-1001. PMID: 12942567

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

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

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

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

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

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

Treatment of cutaneous T cell lymphoma: current status and future directions. 
Am J Clin Dermatol. 2002;3(3):193-215. Review. PMID: 11978140  PubMed

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

Treatment of cutaneous T cell lymphoma: current status and future directions. Am J Clin Dermatol. 2002;3(3):193-215. Review. PMID: 11978140  PubMed