Treatment of stage II cutaneous T-cell lymphoma with interferon alfa-2a and extracorporeal photochemotherapy: a prospective controlled trial.

BACKGROUND: Both interferon alpha and extracorporeal photochemotherapy have been shown to be effective in primary cutaneous T-cell lymphomas (CTCLs). However, no prospective trial has been published on the combination of both treatments, although retrospective investigations suggested a better efficacy than for either interferon or extracorporeal photochemotherapy. OBJECTIVE: Our purpose was to evaluate the efficacy and toxicity of combined interferon alfa-2a with extracorporeal photochemotherapy in a prospective controlled trial. METHODS: A prospective controlled study was performed. Fourteen patients (all male) aged 38 to 72 years with CTCL of the mycosis fungoides type, stage IIa/IIb, and a 72-year-old male patient with a Ki-1 lymphoma were treated twice a month for 6 months with extracorporeal photochemotherapy using oral 8-methoxypsoralen as photosensitizer in combination with interferon alfa-2a subcutaneously 3 times a week in the maximal tolerable dosage (ie, up to 18 x 10(6) U). The effects were investigated by a skin score, staging, histologic score (density of the T-cell infiltrate; from 0 = absent to 3 = heavy), immunohistology, and laboratory investigations including total peripheral T-cell count, CD4/CD8 ratio, and soluble interleukin 2 receptor (sIL-2R). RESULTS: After 6 months, best response was a complete response (CR) in 4 patients, a partial response (PR) in 3, and a stable disease (SD) in 7 of 14 patients (overall response rate [CR + PR] 50%). In responders the time to best response was 4.3 +/- 1.4 months. The skin score decreased from 22.5 +/- 8.1 to 15.1 +/- 11.0 (P <.001), the histologic score decreased from 2.57 +/- 0.51 to 1.21 +/- 0.80 (P <.001). In the lesional skin the percentage of CD4 cells decreased from 75% to 51% (P =.038) and Ki-67-positive cells decreased from 6.7% to 2.4% (P =.001). The total T-cell count/microL decreased from 1018.9 +/- 557.1 to 667.9 +/- 417.9 (P =.012), and the CD4/CD8 ratio also decreased from 1.88 +/- 0.92 to 1.51 +/- 0.67 (P =.038). The sIL-2R levels did not change significantly during the first 4 months of treatment. Among patients of stage IIa the response rate was 60% in contrast to only 25% of those in stage IIb. Side effects were seen temporarily, ranging from grade 0 to grade 3. There was no need for additional therapy, but interferon dose was decreased because of side effects. After 1 year of follow-up the total response rate was 46.2% (6 of 13 patients): 5 of 9 with stage IIa(55.6%) and 1 of 4 with stage IIb (25.0%). CONCLUSION: These results indicate that patients with CTCL stage IIa can achieve a total response rate of 56% with combined interferon alfa-2a and extracorporeal photochemotherapy. Responders seem to experience their best response within the first 6 months of treatment. The treatment is well tolerated and does not cause severe side effects.

Survival of patients with cutaneous T-cell lymphoma after treatment with extracorporeal photochemotherapy.

Few studies have assessed the long-term outcome of patients with cutaneous T-cell lymphoma (CTCL) treated with extracorporeal photochemotherapy (ECP). Our objective was to assess the efficacy, safety, and survival of a cohort of patients with refractory CTCL in stages Ib to III who were treated with ECP. A retrospective study was performed. Twenty patients (19 male, 1 female) aged 38 to 87 years with CTCL of the mycosis fungoides type (n=17) and primary cutaneous Ki-1 lymphoma (n=2) were treated twice a month. Sixteen had an adjunctive treatment with interferon alpha (IFN alpha) s.c. 3 times a week in the maximal tolerable dosage (i.e. up to 21x106). A complete response was achieved in 10 patients, a partial response in three and a stable disease in seven patients (response rate 65.0%). The overall survival was 29.4+/-16.0 months, the event-free survival was 26.2+/-12.4 months, and the progression-free survival was 23. 4+/-12.2 months. Four patients died of causes unrelated to CTCL and two patient died of CTCL. Median survival time was 26 months. No severe side effects were noted. ECP is a safe alternative therapy for CTCL. In particular when combined with IFN alpha it can induce long-term remissions.

Biosurgery in wound healing--the renaissance of maggot therapy.

Chronic wounds are a challenge for modern health care. A basic principle of treatment is the removal of sloughy, necrotic, devitalized tissue to prevent wound infection and delayed healing. Biosurgery (syn. maggot or larval therapy) is a promising adjunct to the whole spectrum of topical treatment methods, in particular for debridement. The term 'biosurgery' describes the use of living maggots on wounds to remove devitalized tissue, decrease the risk of infection and improve wound healing. The present paper gives a brief review of history, entomology, biochemistry and medical indications of biosurgery and the practical handling of maggots. We also provide some clinical data from the literature and our own experience in a wound care unit. Biosurgery is an effective and safe treatment option for debridement and disinfection.

Extracorporeal photochemotherapy in cutaneous lupus erythematosus.

We report two female subjects with therapy-resistant cutaneous lupus erythematosus (LE), one with subacute cutaneous and the other chronic discoid LE, both treated with extracorporeal photochemotherapy (ECP). The responses after six and eight cycles of ECP led to a prolonged remission of 18 and 11 months, respectively. ECP seems to be a treatment option for patients not responding to or showing unwanted side-effects during conventional standard therapy.

[Progressive systemic sclerosis - treatment results of extracorporeal photopheresis]. / Progressive systemische Sklerodermie. Behandlungsergebnisse unter extrakorporale Photopherese.

The treatment of progressive systemic sclerosis (PSS) is still unsatisfactory. We report on clinical, laboratory and immunological findings in 26 patients with PSS (6 males, 20 women) treated with extracorporeal photopheresis (ECP) for 8 cycles in a nonrandomized, uncontrolled study. ECP was performed on two consecutive days once a month. 8-methoxypsoralen concentrations in plasma and buffy coat were monitored by HPLC. We performed a standardized examination programme and determined parameters of inflammation and immune function. Global assessment revealed a partial remission in 18 patients, a stable disease in 8 patients and a slight progression in one patient. In the peripheral blood count a significant increase of CD3-positive NK cells was noted (p=0.03) although the leukocyte count decreased from 2,255 to 1,156 cells/microl. There was a non-significant decrease of elastase (102. 9 vs. 90.4 ng/ml), sulfidoleukotriens (2,255.4 vs. 1,688.9 pg/ml), ICAM-1 (301.9 vs. 276.6 ng/ml), soluble IL-2 receptor (609.0 vs. 422. 3 U/ml), and IL-10 (164.7 vs. 138.7 pg/ml). IL-6 and IL-8 did not show significant changes. The ECP treatment of patients with PSS shows immunomodulatory effects changing levels of pro-inflammatory and cytokine substances. Even after 8 cycles partial remission or stable disease is seen in patients as shown by global assessment and certain clinical symptoms. On the other hand, sufficient data on the long-term outcome are still missing.

Short-time extracorporeal photochemotherapy in the treatment of drug-resistant autoimmune bullous diseases.

BACKGROUND: Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are potentially severe diseases. In drug-resistant PV and pemphigus foliaceus, long-term adjuvant treatment with extracorporeal photochemotherapy (photopheresis, ECP) has been reported to induce remission. Only limited numbers of patients have been reported so far. No information about the effectiveness in drug-resistant BP is available. PATIENTS AND METHODS: Seven patients with drug-resistant autoimmune bullous diseases have been referred to the photopheresis center of Jena (3 x PV, 3 x BP, 1 x pemphigus foliaceus). The age ranged from 31 to 85 years. ECP was performed on 2 consecutive days once a month. Oral 8-methoxypsoralen was used as photosensitizer. Previous immunosuppressive treatment with either prednisolone or prednisolone/ azathioprine was continued. RESULTS: Complete remission (absence of skin or mucous membrane lesions) was achieved in the 6 patients with PV and BP after 1-4 cycles. In the patient suffering from pemphigus foliaceus, a partial remission (> 50% improvement) was observed; in all except this patient, the immunosuppressive treatment could be tapered. Long-term remission was achieved. No severe side effects were observed. The treatment was well tolerated. CONCLUSIONS: Short-time ECP is an effective and safe adjuvant treatment for patients with drug-resistant autoimmune bullous diseases. It can induce remission and allows dose tapering of the immunosuppressive drugs.

Plasma and buffy coat concentration of 8-methoxypsoralen in patients treated with extracorporeal photopheresis.

Recently, a new therapy involving an extracorporal activation of orally administered 8-methoxypsoralen (8-MOP), photosensitizing furocoumarin, is established for the treatment of different skin diseases, extracorporeal photopheresis (ECP). The pharmacokinetic profile of 8-MOP has been pursued as part of a clinical study which should assess the efficacy of ECP in patients with progressive systemic sclerosis and cutaneous T-cell lymphoma. The enormous intra-individual variations proofed for plasma as well as buffy coat concentration are unfavourable for oral 8-MOP therapy. Therefore, the introduction of liquid 8-MOP formulation that allows the direct administration of the drug in to the treatment bag of the ECP device is challenging.

Drug monitoring of orally administered 8-methoxypsoralen in patients treated with extracorporeal photopheresis.

Recently extracorporeal photopheresis (ECP), a new therapy involving extracorporeal activation of orally administered 8-methoxypsoralen (8-MOP), has been established for the treatment of different skin diseases. The pharmacokinetic profile of 8-MOP has been pursued in a clinical study which aimed to assess the efficacy of ECP in patients with progressive systemic sclerosis and cutaneous T-cell lymphoma. However, the enormous intraindividual variations in plasma as well as buffy coat concentrations affect the efficacy of oral 8-MOP therapy. Therefore, the introduction of a liquid 8-MOP formulation enabling the direct administration of the drug into the treatment bag of the ECP device is challenging.