The Prognostic Significance of Delayed Hypersensitivity to Dinitrochlorobenzene and Mechlorethamine Hydrochloride in Cutaneous T Cell Lymphoma

Abstract

Recent studies suggest that cells elaborating type 1 cytokines are important mediators of anti-tumor cell-mediated immunity in cutaneous T cell lymphoma. Type 1 cell-mediated immune responsiveness was assessed in 276 patients with cutaneous T cell lymphoma (mycosis fungoides and Sézary syndrome) using 2,4-dinitrochlorobenzene (DNCB) skin testing as part of the initial evaluation. The overall rate of sensitization after one and two DNCB challenges was 32% and 67%, respectively, which is much decreased compared with the expected rate of more than 95% for normal individuals. Moreover, the frequency of DNCB sensitization and allergic contact dermatitis to topically applied mechlorethamine decreased with advancing stage of disease. In addition to the expected strong correlation with stage, we observed that patients who were DNCB test positive were significantly less likely to experience disease progression and had a better overall prognosis compared with DNCB-negative patients. These results support the concept that cell-mediated responses are important in cutaneous T cell lymphoma, and that augmentation of these responses would be therapeutically beneficial.

Mycosis Fungoides

“…On the other hand, clinical experience suggests that many patients with MF, in particular those with stage Ia and perhaps also many with stage Ib disease, may have stable disease for decades, and that only a proportion of patients with MF progresses and will develop extracutaneous disease. Consistently, the results of this and other recent studies 10,12,13 indicate that the risk of disease progression within the first 10 years after diagnosis is about 5% to 10% for patients with stage Ia and between 17% and 39% for patients with stage Ib disease. In patients with more advanced stages of MF, the risk of disease progression was higher and the duration until progression shorter (Tables 2 and 5).…”

“…Tumor stage MF is often associated with a poor prognosis. However, this and other studies 11,12,14 clearly indicate that patients with skin tumors without concurrent extracutaneous disease (stage Ic) still have a diseaserelated 5-year survival of approximately 70% to 80%. Whether patients with enlarged, but histologically uninvolved, lymph nodes (stage II) have a more unfavorable prognosis compared with patients without clinically enlarged lymph nodes is a matter of controversy.…”

“…There is, therefore, no evidence that the lymph nodes of these patients with stage II MF were actually involved, which leaves the more unfavorable prognosis of this group unexplained. In the literature, the following prognostic variables have been described: stage of disease, [3][4][5][11][12][13][14] age, 2,10,12,13 race, 2 response to initial treatment, 3,10,13 and prior malignant neoplasm. 2 In the present study, stage at diagnosis (ie, the presence of extracutaneous disease and the type of skin involvement), complete remission after initial treatment, and the presence of follicular mucinosis proved independently predictive of disease-specific survival and disease progression.…”

Skin hyporeactivity in relation to patch testing

“…Several articles report this for patients with altered immune conditions: cancer (1)(2)(3)(4)(5), viral infections (6-9), Whipple's disease (10), mycosis fungoides (8,(11)(12)(13)(14) and sarcoidosis (15)(16)(17)(18)(19). These findings are referred to as skin anergy, a faulty cellular immune response and the opposite of allergy.…”

“…Prior to a single application of a selected contact Table 1. Observations of skin hyporeactivity/anergy Observations of skin hyporeactivity/anergy UV radiation (13-14, 26, 28) corticosteroid therapy (23)(24)(25)(26) immunomodulator treatment (22,(26)(27) sarcoidosis (15)(16)(17)(18)(19) cancer (1-5) viral infection (7), HIV (6), measles (8-9) Whipple's (10) mycosis fungoides (11)(12)(13)(14) allergen under a Finn Chamber for 24 h, the Ginkgo formulation was applied to intact skin 2¿ daily for 2 weeks. Visual scoring was performed 2 and 3 days after patch removal.…”