Secondary cancers, comorbidities and mortality associated with nitrogen mustard therapy in patients with mycosis fungoides: a 30-year population-based cohort study.

BACKGROUND: Topical nitrogen mustard is a widely used therapy in patients with mycosis fungoides (MF). However, it remains controversial whether nitrogen mustard therapy is associated with increased risk of secondary cancers and chronic pulmonary diseases in patients with MF. OBJECTIVES: To assess the risk of secondary cancers, comorbidities, mortality and cause-specific mortality in patients with MF treated with nitrogen mustard compared with patients not receiving this treatment. METHODS: Linking the Danish nationwide registries in a 30-year population-based cohort study, we compared 110 patients with MF from a regional Danish centre using nitrogen mustard treatment with 193 patients from Danish centres not using nitrogen mustard. The two cohorts were compared by Cox regression analysis. RESULTS: Overall, secondary cancers were not significantly increased [hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.46-1.56], and subanalyses showed no significantly increased risk of nonmelanoma skin cancers, malignant melanomas or cancers in the respiratory organs in the nitrogen mustard-treated cohort. Furthermore, we found no significantly increased risk of any category of comorbidity, including chronic pulmonary diseases, in patients treated with nitrogen mustard (HR 0.93, 95% CI 0.48-1.81). Moreover, mortality and cause-specific mortality did not significantly differ between the two cohorts. CONCLUSIONS: This study does not support any previous suspicion of increased risk of secondary cancers and chronic pulmonary diseases among patients with MF treated with nitrogen mustard. Furthermore, mortality and cause-specific mortality were not influenced by nitrogen mustard treatment. Thus our findings indicate that topical nitrogen mustard is a safe therapy in patients with MF.

Topical nitrogen mustard therapy in patients with mycosis fungoides or parapsoriasis.

BACKGROUND: Topical nitrogen mustard is a chemotherapeutic agent used in treatment of mycosis fungoides (MF). OBJECTIVE: To evaluate the response and side effects in patients with MF and parapsoriasis treated with topical nitrogen mustard. METHODS: A retrospective study of treatment response in 116 patients diagnosed with MF and 71 patients with parapsoriasis and treated with topical nitrogen mustard from 1991 to 2009. RESULTS: Overall response rate and complete response (CR) rate was 91.4% and 53.4% in patients with MF and 90.1% and 40.8% in patients with parapsoriasis, respectively. Relapse following CR was observed in 67.7% in patients with MF and 62.1% in patients with parapsoriasis. Freedom-from-relapse was higher in patients with T1-T2 than in T3 disease (P < 0.01). Progressive disease (PD) occurred in 25.0% and 26.8% in patients with MF and parapsoriasis, respectively. Progression-free survival was similar in patients with T1-T2 compared with T3 (P = 0.79) and T4 disease (P = 0.22) and lower in patients with parapsoriasis with <10% than >10% skin involvement (P = 0.05). CONCLUSION: The present study confirms that topical nitrogen mustard is a safe and effective therapy. The treatment response in patients with parapsoriasis was not statistically different from the response in patients with MF. This supports, that parapsoriasis is not a distinct entity, but an early stage of MF. Nitrogen mustard should therefore still be considered as an important treatment modality in patients with early stages (parapsoriasis) and later stages of MF either as monotherapy or in combination with other topical or systemic therapies.

Low-dose total skin electron beam therapy as a debulking agent for cutaneous T-cell lymphoma: an open-label prospective phase II study.

BACKGROUND: Total skin electron beam therapy (TSEBT) is a powerful treatment for cutaneous T-cell lymphoma (CTCL). Based on the occurrence of relapses with low radiation doses, doses of 30-36Gy are commonly used but most patients still eventually relapse and repeat treatment courses are limited due to the cumulative toxicity. Complete response (CR) rates are about 60-90% for T2-4 stages with a 5-year relapse-free survival of 10-25% for stages IB-III. OBJECTIVES: To evaluate prospectively the efficacy of low-dose TSEBT (10Gy) in terms of complete cutaneous response rate, overall response rate and response duration in CTCL. METHODS: Ten patients with stage IB-IV mycosis fungoides (MF) were treated in an open-label manner with four fractions of TSEBT 1Gy weekly to a total skin dose of 10Gy. Treatment responses were assessed at 1 and 3months after treatment and subsequently at least every 6months for a total period of 2years or to disease relapse or progression. RESULTS: Patients achieved an overall response rate of 90%. The rate of CR or very good partial response (VGPR; <1% skin affected with patches/plaques) was 70%. The median response duration was 5·2months (range 83-469days) for CR and VGPR. Adverse effects were generally mild to moderate in severity. CONCLUSIONS: Low-dose TSEBT (10Gy) gave a satisfactory response rate and was well tolerated in patients with MF stage IB-IV. Future studies should determine if the combination of low-dose TSEBT with other agents could increase the rate of CR and response duration.

Topical nitrogen mustard therapy in patients with Langerhans cell histiocytosis.

BACKGROUND: Langerhans cell histiocytosis (LCH) is characterized by abnormal proliferation and infiltration of Langerhans cells in different organs. The skin is frequently involved either as unisystem or multisystem disease. OBJECTIVES: To review the clinical response and side-effects of nitrogen mustard therapy in LCH in children and adults with unisystem or multisystem disease. PATIENTS AND METHODS: This retrospective study includes 10 children and four adults with LCH, treated with nitrogen mustard from 1975 to 2010. The median extent of skin involvement was 46% (range 5-100%). RESULTS: Overall, 13 patients had complete or partial response. Although eight patients achieved a complete response with a median time of 12·3months (range 36 days to 1·9 years), six of these patients ultimately relapsed. One patient, who had unisystem disease limited to the skin, initially showed progression of her cutaneous lesions with nitrogen mustard treatment. Although subsequently the cutaneous lesions completely regressed, concomitant systemic involvement was noted. Four other patients similarly experienced improvement of their skin lesions with treatment, but also exhibited progression of the LCH systemically. The patients were treated with other therapies prior and adjunctive to nitrogen mustard. However, five patients had progression to other organs, despite regression of skin lesions, which supports that the treatment effect in the skin is related to topical nitrogen mustard. Six patients developed contact dermatitis to nitrogen mustard. CONCLUSIONS: Topical nitrogen mustard can be an effective and safe therapy in both children and adults with cutaneous LCH, although relapses are common.