Complete remissions of mycosis fungoides lymphoma induced by topical nitrogen mustard (HN2). Control of delayed hypersensitivity to HN2 by desensitization and by induction of specific immunologic tolerance

Abstract

Sustained complete remissions have been achieved with whole body continuous topical applications of aqueous solutions of mechlorethamine (HN2), and supplemental intralesional injections of tumors. Of 76 patients entered into the treatment study over a 4‐year period, approximately 50% are free of detectable disease, 13 of whom have had remissions extending now beyond 2 years. Most patients experiencing complete remissions had disease confined to skin, without lymph node or visceral involvement, when topical therapy was initiated. Delayed hypersensitivity to HN2, a frequent occurrence, has been abolished in sensitized patients by means of daily minute I.V. doses of the drug. Induction of specific immunologic tolerance to HN2, prior to topical treatment, has been achieved by means of several weekly I.V. injections of similarly minute doses of the drug.

Current Problems in Mycosis Fungoides and Sezary Syndrome

“…The patients are readily sensitized to locally applied dinitrochlorobenzene (56) and, during treatment, to nitrogen mustard (57). Drug reactions and contact dermatitis occur readily in patients with MF and are often the cause of erythroderma.…”

“…In recent years, investigators have been adopting a more aggressive attitude toward the treatment of MF (3,57,(74)(75)(76), based on the following assumptions:…”

“…Recently used topical agents in established MF include fluorinated corticosteroids (77,78), nitrogen mustard (57,76), nitrosourea compounds (79,80), and topical cutaneous sensitizers (81,82). Clinicians have long used topical corticosteroids in the treatment of premycotic eruptions, but studies have shown that fluorinated , corticosteroid creams, when applied with occlusive techniques, will cause regression of mild to moderately advanced lesions (77,78).…”

“…The adequacy of response is proportional to the concentration of the steroid, but the regression of lesions is temporary and there is ultimate recurrence. Nitrogen mustard (HN2) was first employed for the topical therapy of MF more than 20 years ago and now assumes a major role in the treatment of MF confined to the skin (57,76). Various treatment schedules have been employed; 10-40 mg of HN2 is dissolved in 50-60 ml of water, and the solution is applied to the entire body surface at intervals ranging from twice daily to two or three times a week.…”

“…After regression of lesions, the frequency of HN2 applications can be reduced to once weekly for maintenance, and this is continued indefinitely. This form of therapy has produced an encouraging number of sustained remissions (57).…”