Killer Immunoglobulin-Like Receptor Transcripts Expression for the Diagnosis of Epidermotropic Cutaneous T Cell Lymphoma (KIR)

Analysis of Killer Immunoglobulin-like Receptor Transcripts Expression for the Diagnosis of Epidermotropic Cutaneous T-cell Lymphomas (Mycosis Fungoid and Sézary Syndrome) in Patients With Erythroderma or Erythematous Patches/Plaques.

The most frequent cutaneous T-cell lymphomas (CTCL) are mycosis fungoid and Sezary syndrome. The diagnosis of these lymphomas is difficult using current methods, especially because numerous benign dermatological conditions can mimick CTCL both clinically and under microscopic examination. Recently, the KIR receptor CD158k has been shown to be a marker for Sezary syndrome in both the blood and skin. We hypothesize that other receptors from the same family may help fro the diagnosis of these lymphomas. To address this issue, we will study the expression of all known KIR receptor in the skin of patients presenting with a skin eruption, which may correspond to either a cutaneous T-cell lymphoma or a benign dermatological disease. The final diagnosis will be established by a panel of experts, allowing constitution of 2 groups of patients : the cutaneous T-cell lymphoma group, and the benign inflammatory disease group. The expression of the different KIRs will be analyzed in both group in a blinded fashion, in order to determine whether one or a several KIRs may be differentially expressed.

Study Overview

• Status: Completed
• Conditions: Dermatitis; Sezary Syndrome; Dermatitis, Exfoliative; Mycosis Fungicides
• Intervention / Treatment: Other: Detection of KIR receptor by RT PCR

Detailed Description

Background : The most frequent cutaneous T-cell lymphomas (CTCL) are mycosis fungoid and Sezary syndrome. Both are due to the proliferation of a CD4+ T-cell clone in the skin, associated with a blood involvement in Sezary syndrome. Mycosis fungoid clinically presents as a patches or plaques dermatitis and Sezary syndrome as an exfoliative dermatitis. The diagnosis of these lymphomas is difficult using current methods, especially because numerous benign dermatological inflammatory conditions can mimick CTCL both clinically and under microscopic examination. Recently, the KIR receptor CD158k has been shown to be a marker for Sezary syndrome in both the blood and skin. We hypothesize that other receptors from the same family may help fro the diagnosis of these lymphomas.

Aim of the study : to determine if one or a panel of KIR(s) receptor(s) may help for the differential diagnosis between cutaneous T-cell lymphoma (CTCL) and benign inflammatory dermatoses.

Subjects selection : all patients presenting to an investigator, member of the GFELC experts group ("French Group Study Cutaneous Lymphoma"), with either an exfoliative or patch/plaque dermatitis with a clinical suspicion of CTCL will be enrolled.

Number of subjects : A total of 550 patients could be recruited by the GFELC, including 180 CTCL (60 Sezary syndrome and 120 mycosis fungoid) and 370 inflammatory diseases (240 patch dermatitis and 130 exfoliative dermatitis).

Inclusion period : patients will be included during a 2 years period and will be followed during 6 months. Total study length will be 30 months.

Interventions : 1) 3 mm punch skin biopsy for all patients 2) 10 ml blood sample for patients with exfoliative dermatitis Methods : Following initial and 6 month follow-up evaluations, patients will be classified in one of the following groups : the cutaneous T-cell lymphoma group, and the benign inflammatory disease group. The expression of all known KIRs receptors (KIR2DL1 (CD158a), KIR2DL2 (CD158b1), KIR2DL3 (CD158b2), KIR2DL4 (CD158d), KIR2DL5 (CD158f), KIR3DL1 (CD158e1), KIR3DL2 (CD158k), KIR2DS1 (CD158h), KIR2DS2 (CD158j), KIR2DS4 (CD158i), KIR2DS5 (CD158g), KIR3DS1 (CD158e2)) will be evaluated using reverse transcription and quantitative polymerase chain reaction in all skin and blood samples, in a blinded fashion. For blood samples, the analyses will be performed on CD4+ T-cell sorted using magnetic beads.

Outcome measures : The main outcome measure will be the differential expression of one or a panel of KIR(s) receptor(s) between CTCL and benign inflammatory diseases. Secondary outcome measure will be a differential quantitative expression of one or a panel of KIR(s) receptor(s) between the two groups.

• Study Type: Interventional
• Enrollment (Actual): 495
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Creteil, France, 94010
    • Groupe hospitalier Henri Mondor - Albert Chenevier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed consent
• Subacute/chronic dermatitis (>7 days) with clinical suspicion for cutaneous T-cell lymphoma
• No past history of lymphoma or other hematologic malignancy
• Skin biopsy for routine histology at inclusion
• Cutaneous T-cell clonality analysis at inclusion
• Sezary cell count on routine blood smear examination in case of erythroderma
• Blood T-cell clonality analysis at inclusion in case of erythroderma
• Age<18 years
• Skin biopsy for routine histology at inclusion (Possibility, in the 6 previous months of inclusion without any specific treatment other taht local corticoids- amendment n°4)
• Cutaneous T-cell clonality analysis at inclusion (Possibility, in the 6 previous months of inclusion without any specific treatment other taht local corticoids- amendment n°4)
• Realization of a preliminary medical examination
• Sezary cell count on routine blood smear examination in case of erythroderma (Possibility, in the 6 previous months of inclusion without any specific treatment other taht local corticoids- amendment n°4)
• Blood T-cell clonality analysis at inclusion in case of erythroderma (Possibility, in the 6 previous months of inclusion without any specific treatment other taht local corticoids- amendment n°4)

Exclusion Criteria:

• Adults under tutelage
• Subject not affiliated at the French National health and pensions organization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 1; Detection of KIR receptor	Other: Detection of KIR receptor by RT PCR; Detection on biopsy cutaneous (3mm) and on blood sample of 30 ml

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Differential expression of one or a panel of KIRs transcript(s) between epidermotropic cutaneous lymphoma and inflammatory diseases	at the inclusion

Secondary Outcome Measures

Outcome Measure	Time Frame
Difference(s) in the quantitative expression of one or a panel of KIRs transcript(s) between epidermotropic cutaneous lymphoma and inflammatory diseases	at the inclusion

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Nicolas Ortonne, MD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: September 5, 2008
• First Submitted That Met QC Criteria: September 5, 2008
• First Posted (Estimate): September 8, 2008

Study Record Updates

• Last Update Posted (Estimate): August 22, 2012
• Last Update Submitted That Met QC Criteria: August 21, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: Diagnosis; Sezary syndrome; Polymerase chain reaction; Receptors KIR; Lymphoma T-cell cutaneous; Mycosis fungicides; Differential diagnosis from dermatitis
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Infections; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Disease; Bacterial Infections and Mycoses; Skin Diseases, Eczematous; Lymphoma; Syndrome; Dermatitis; Mycoses; Lymphoma, T-Cell; Lymphoma, T-Cell, Cutaneous; Sezary Syndrome; Dermatitis, Exfoliative
• Other Study ID Numbers: P070153