Long-term therapy of HIV-associated Kaposi''s sarcoma with recombinant interferon α-2a

Five young male patients with HIV-associated Kaposi's sarcoma (KS) were treated with recombinant interferon alpha 2a (rIFN-alpha-2a) over a period of 2-2.5 years. An IFN dose of 18 x 10(6) IU was given subcutaneously every day during the first 3 months of treatment and then on alternate days. Additional treatment with radiotherapy and laser therapy was given and, in some cases, isolated skin nodules were excised. Within 7 months of initiation of therapy one patient had a complete remission of his tumours, however, tumour progression recurred after the patient discontinued treatment. In another patient the tumour cleared within 9 months of rIFN therapy, and after 52 months he is still free of KS. The condition of a third patient tended to become stabilized during the first 6 months of therapy, but after 60 months there has been a slow progression. The fourth and fifth patients died 25 and 28 months, respectively, after the histological diagnosis of KS and the initiation of treatment. While on therapy with rIFN-alpha-2a, no life-threatening opportunistic infections occurred. The side-effects were mostly well tolerated, and no severe changes in haematological parameters were caused by the therapy.     

Response of severe systemic mastocytosis to interferon alpha

Six patients with documented systemic mast cell disease were enrolled in a 1-year, phase I study to determine the possible benefits of interferon alpha-2b (IFN-α). IFN-α therapy was begun at a dosage of 0.5 million units/day (MU/day) by subcutaneous injection and increased, as tolerated, to 3.0 MU/day. Subsequent dose modifications were made based on clinical tolerance and response. No immediate, adverse reactions to IFN-α occurred. Several patients showed symptomatic improvement. In two patients ascites resolved and did not recur. Two other patients reported improved energy levels and had decreased size of retroperitoneal, mesenteric and retrocrural nodes. One patient failed to benefit and died shortly after completing 12 months of therapy. Bone marrow mastocytosis decreased by 5% to 10% after 12 months of therapy with IFN-α. Although five of the six patients had a decrease in the urinary excretion of 1-methyl-4-imidazole acetic acid, serum tryptase values did not appreciably change in any patient. Side-effects from IFN-α included hypothyroidism, thrombocytopenia and depression. It is concluded that although treatment with IFN-α was associated with a decline in bone marrow mastocytosis and reduced excretion of histamine metabolites, prolonged therapy may be needed and dose-limiting side-effects are frequent.     

Classical form of Kaposi sarcoma: immunology and interferon therapy

T-lymphocytes and their subsets were determined in three patients with classical Kaposi's sarcoma. A reduction of pan-T-lymphocytes, including both a reduction of T-helper and T-suppressor cells, was found in one patient. None of the patients showed a reduction of the T-helper/T-suppressor cell ratio, as described in the lymphadenopathic disseminated type of Kaposi's sarcoma. Intradermal testing with tuberculin and trichophytin gave no indication of humoral immunodeficiency or anergy. In addition to electron beam irradiation, one female patient was treated with rIFN-alpha-interferon, 6 X 10(6) IU 3 times a week over a period of 3 months, and 18 X 10(6) IU 3 times weekly over 1 month. Under this therapy, irradiated as well as nonirradiated lesions become flatter, reduced in size and faded. The number of T-suppressor cells diminished.     

Intralesional human leukocyte interferon treatment alone or associated with IL-2 in non-AIDS related Kaposi's sarcoma.

Patients with classical European Kaposi's sarcoma were treated by intra- and peritumoral injections of human alpha leukocyte interferon (IFN) (12 cases) or, alternatively, with IFN and naturally synthesized IL-2 (8 cases). All the patients were HIV negative with tumors which had been present for at least six months. In each patient, one tumor received 1 ml (50,000 IU) IFN alone or alternatively associated with 1 ml IL-2 twice a week for 4-6 weeks; another nodule situated 10-12 cm away was considered as a control and remained uninjected. The clinical follow-up revealed that, in the same patient in the same anatomical area, the treated nodule was cured in all the investigated cases; the untreated one was not. These data strongly suggest that IFN is the factor responsible for the involution and final cure of these Kaposi tumors treated by perilesional inoculations. Association with IL-2 (and certainly also other interleukins) increases the beneficial clinical activation of the tumor involution. Histological examination showed that important histopathological changes occur in the treated nodules: complete disappearance of the Kaposi's aspect, fibrosclerous modifications progressively replacing the fibroblasts characteristic of Kaposi's sarcoma, abundant infiltrations of leukocytes, especially lymphocytes and necrotic patches, often with hemorrhagic centers. IL-2 association seems to especially induce this last type of histological phenomenon.     

Kaposi肉瘤患者血清人类疱疹病毒8型的检测

目的：了解干扰素治疗Kaposi肉瘤近期疗效及其对血清HHV-8 DNA检测的影响。方法：主要应用干扰素治疗4例无明显内脏损害的新疆经典型Kaposi肉瘤患者，同时在治疗前后采用PCR法检测血清HHV-8 DNA特异性片段。结果：4例患者经干扰素治疗45d后，均有不同程度的近期疗效，主要表现在皮损色泽变暗、结节和斑块变软、变平，部分小结节消退，且均无新皮损发生。但淋巴水肿无明显改观。血清HHV-8 DNA特异性片段经PCR检测，治疗后全部转阴。结论：干扰素治疗可有效地清除Kaposi肉瘤患者血清中HHV-8感染，能缓解病情，防止Kaposi肉瘤多灶病状的发生。     

Ambulatory treatment of metastatic melanoma associating subcutaneous dacarbazine, interferon α and interleukin-2

Background Recent studies have shown that interleukin–2 (IL2) is less toxic when administered subcutaneously than intravenously. Moreover interferon α and Dacarbazine could increase the efficiency of IL2. Patients and methods Nineteen ambulatory patients with metastatic melanoma (1 stage 111 and 18 stage IV) were treated with an association of dacarbazine 400 mg/m², interferon α_2a (Roferon) 9 × l0⁶ IU 3 times per week administered subcutaneously and recombinant interleukin-2 (IL–2) (Eurocetus) 3 × 10⁶ IU five days per week for two weeks per month subcutaneously. The treatment consisted of 2 induction cures separated by a one-month interval followed by evaluation studies. Results At the end of the induction phase. 2 complete and 3 partial responses (response rate 26.2%) were observed. These responses were obtained in patients with sinus (1 case), skin (3 cases), lymph node (2 cases), bone (1 case) and liver (I case) targets. The mean response period was 10 months for the 2 complete responses. No patients had grade 4 toxicity, and treatment was stopped for only one patient. Painful subcutaneous nodules frequently (23%) formed at the injection site. Conclusion The association of subcutaneously administered dacarbazine, interferon α and IL2 would thus seem of interest for the treatment of metastatic melanoma. Moreover, toxicity is tolerable and compatible with ambulatory treatment ensuring the patient a decent quality of life.     

Successful treatment of verruca plantaris with a single sublesional injection of interferon-α2a

Background.  Interferons are molecules with antiviral effects, which have been used for the treatment of verruca for many years.
Aims.  To determine if sublesional interferon (IFN)-α injection offers an effective alternative treatment for common warts.
Methods.  We compared the results of single-dose sublesional IFN application in different types of verruca and with placebo for the treatment of single verruca plantaris lesions. In total, 53 patients (mean age 22.6 years) were enrolled in the study. Of these, 45 patients received a single sublesional injection of 4.5 MU IFN-α2a (three study groups), and eight patients with single verruca plantaris lesions were injected with physiological saline as placebo (control group). As local anaesthesia, liquid nitrogen was sprayed only on to the injection site for 3–4 s. The injection was made directly under the lesion through the border of the lesion, at with approximately a 45° angle from healthy skin.
Results.  At the 12-month follow-up in the group of patients with single verruca plantaris, there were 19 complete cures (7.2%) and 2 partial responses (8.3%), and 3 patients (12.5%) had no response. In the control group, only 2 patients (25%) had a partial response to treatment.
Conclusions.  These results suggest that a single sublesional dose of 4.5 MU IFN-α may be of value in the treatment of patients with verruca, especially in those with single verruca plantaris lesions.     

干扰素中和抗体对重组α干扰素治疗尖锐湿疣疗效的影响

目的观察干扰素中和抗体(NA)对重组α干扰素(IFN-α)治疗尖锐湿疣疗效的影响及临床意义。方法86例尖锐湿疣患者治疗前采用抗病毒生物中和法测定NA阴性者,经微波或CO2激光治疗后给予局部干扰素治疗,每次3×106IU,每周2次,疗程3~9个月(平均6个月),疗程中定期测定NA。结果86例患者治疗后NA阳性11例(12.79%),其中治疗后3,4,5,6及6个月后检出分别是1,2,3,2例及3例。NA阳性组HPV复发率(72.72%)高于NA阴性组(25.33%);临床治愈率(27.27%)低于NA阴性(74.67%),两组差异有显著性(P<0.01)。结论IFN-α治疗尖锐湿疣NA阳性率不高,但NA可以影响IFN-α的疗效。     

Panniculitis after subcutaneous injection of interferon beta in a multiple sclerosis patient

BACKGROUND: Interferons are used in the immune therapy of multiple sclerosis, Kaposi's sarcoma, hepatitis and melanoma based on their antiviral, immunoregulatory and antitumor activities. We report a rare side effect observed during treatment of multiple sclerosis with subcutaneous interferon beta injections. OBSERVATIONS: A 44-year-old patient diagnosed with multiple sclerosis received immune therapy with 6 Mio IU recombinant interferon-beta (IFN-beta) every other day. After 4 years of subcutaneous interferon injections painful indurations appeared directly at and adjacent to the injection sites on the thighs, arms and abdomen. Pain in the thighs made walking almost impossible and required therapy with opiates. After changing to another interferon-beta medication the symptoms improved. Subsequent treatment with doxycycline for 3 weeks was of no additional benefit. CONCLUSIONS: Panniculitis at the injection sites is a rare event but has a significant impact on the quality of life during interferon therapy.     

Long-term effects of interferon alpha 2A treatment in Behçet's disease

BACKGROUND: Between May 1995 and April 1996, 20 patients with Beh?et's disease were successfully treated with interferon alpha(2a) (IFN-alpha(2a)) 9 million IU/day three times a week and 16 patients with colchicine 1.5 mg/day orally for 3 months. OBJECTIVE: To study the long-term effects of IFN treatment in Beh?et's disease. METHODS: Between the years of 1996 and 1999, the patients were followed up every 3 months or whenever indicated. Retrospective evaluation was performed. RESULTS: In 56% of the patients with complete remission or partial remission at the end of IFN-alpha(2a) treatment, long-term remissions ranging from 36 to 48 months were observed. CONCLUSION: IFN-alpha(2a) treatment is an effective treatment modality in Beh?et's disease with the advantage of inducing prolonged remissions.     

Facial kaposi's sarcoma. Palliative treatment with cryotherapy, intralesional chemotherapy, low-dose roentgen therapy and camouflage]

Facial Kaposi's sarcoma is a severe psychological problem for HIV-infected patients if systemic chemotherapy or interferon therapy is not possible. To help these patients, it is important to offer a palliative treatment that is suitable for outpatients and is not complicated by severe side-effects but still yield satisfactory cosmetic results. A total of 65 patients with 216 facial Kaposi's sarcomas were treated with cryosurgery (92 tumours, 29 patients), intralesional chemotherapy with vincristine (28 tumours, 12 patients), radiotherapy (87 tumours, 15 patients) and camouflage (multiple tumours, 9 patients). Cryosurgery is the treatment of choice for small (less than 1 cm) macular or slightly nodular Kaposi's sarcoma. Larger nodular tumours are better treated by intralesional chemotherapy (single doses of 0.01-0.1 mg vincristine per tumour) or low-dose radiotherapy (3-4 x 4 Gy). These palliative treatment methods are not indicated in cases of rapid tumour progression and dissemination; in such cases, camouflage (covering the tumours with water-resistant make-up) is helpful as a local palliative measure.     

A patient with plaque-stage mycosis fungoides has successfully been treated with long-term administration of IFN-γ and has been in complete remission for more than 6 years

Summary We report the successful treatment of a patient with plaque-stage mycosis fungoides with long-term and intravenous administration of recombinant human interferon-γ (IFN-γ) and discuss the possible mechanisms of this therapy.
A 55-year-old female patient had been resistant to existing treatments and had suffered repeated exacerbations over a 5-year period. Four weeks after initiation of 2 × 10⁶U/day of IFN-γ. a > 10% decrease in the affected surface area was noted. Twenty-two weeks after the administration of 228 × 10⁶U of IFN-γ, complete remission (CR) was obtained. The CR continued for 13 weeks, but this was followed by an exacerbation. The second CR was obtained after the IFN-γ dosage was increased to 16 × 10⁶U/week. The dosage was then gradually reduced by 2–4 × 10⁶U every 2 or 3 months. She was treated with a total dose of 2814 × 10⁶ of IFN-γ. She has been followed up for more than 6 years, and there has been no recurrence of mycotic skin lesions nor any visceral involvement. During therapy, no serious side-effects were noted.
Long-term administration of IFN-γ is useful for the treatment of patients with intractable mycosis fungoides. A gradual decrease in the dose of IFN-γ is important for maintaining remission.     

Treatment of basal cell carcinoma with intralesional interferon

Eight patients with basal cell carcinomas were treated with recombinant alpha-2 interferon. Each patient had a biopsy-proved basal cell carcinoma of the nodular or superficial type that was injected intralesionally three times a week for 3 weeks (9 total injections) with 1.5 X 10(6) IU (0.15 ml) of alpha-2 interferon per injection (total dose, 13.5 X 10(6) IU). Excisional biopsy 2 months after completion of therapy revealed no evidence of basal cell carcinoma in any patient. Minimal side effects were observed. In these eight patients alpha-2 interferon was therefore an effective and safe modality of treatment. The encouraging results of this pilot study suggest that additional evaluation of interferon in the treatment of basal cell carcinoma is warranted.     

Hemorrhagic Kaposi sarcoma. Successful treatment with IFN-alpha

A 76-year-old woman with atypical hemorrhagic Kaposi sarcoma is presented. The patient was treated with recombinant interferon alpha-2b (3,000,000 IU) subcutaneously, three times weekly for 6 months and twice weekly as maintenance dose for 14 months with excellent response and no recurrence after a 7 years of follow-up.     

Intralesional recombinant alpha 2B interferon in the treatment of human papillomavirus-associated cervical intraepithelial neoplasia.

Twenty-four patients with human papillomavirus (HPV)-associated cervical intraepithelial neoplasia (CIN); of whom 13 had CIN 1, 8 had CIN 2, and 3 had CIN 3; were treated with recombinant alpha 2b interferon (IFN) by intraperilesional injections. The dosage given was 3 x 10(6) international units per day, 3 days per week for 3 weeks. In situ hybridization was carried out for HPV types 6/11 and 16/18. One year after treatment, complete response was observed in 8 (33%) cases, partial regression in 14 (58%) cases, persistence in 2 (8%) cases (in which case traditional surgical therapy was performed), and progression in none of the cases. Adverse effects (asthenia, fever, chills, and headache) were observed in 20 (83%) cases. None of the patients had myelodepression. Intraperilesional treatment of HPV-associated CIN with recombinant alpha 2B IFN does not appear to be a valid substitute for traditional treatment, but it could be considered in certain cases when surgery is not advised.     

Disseminated mucocutaneous Kaposi sarcoma in AIDS. Clinical and therapeutic experiences in 13 patients

Since 1980 a new epidemic form of disseminated mucocutaneous Kaposi's sarcoma (KS) with a progressive clinical course has been observed in populations at risk. Since 1982, 13 cases of AIDS-associated KS have been seen in our department; all of them were in young homosexual males with circulating HIV antibodies and a reduction in the ratio of T-helper to T-suppressor lymphocytes (0.05-1.3). Following systemic treatment with recombinant alpha A-interferon (rIFN-alpha A) over a period of 6 months (18 million IU/day for 3 months; later 18 million IU/3 X weekly) together with other concomitant measures (superficial X-ray radiation, argon laser radiation, surgical excision of isolated lesions) we registered complete remission of the remaining lesions in 2 cases, progression of the disease in 4 cases, and at least temporary stabilization of the disease in 7 cases. In 4 patients opportunistic infections occurred during rIFN treatment: Pneumocystis carinii pneumonia (PCP) with lethal outcome in 2 cases, atypical mycobacteriosis in 2 cases, and Legionella pneumoniae infection in 1 case. Two additional deaths were registered due to PCP appearing during the post-treatment period. Life-threatening virus infections were not observed during rIFN treatment. Out of 9 patients receiving prophylactic trimethoprim/sulfamethoxazole medication, only 1 developed allergic exanthema as a result of this drug combination. Occasionally, rIFN-induced leukopenia was seen and pronounced thrombocytopenia appeared in 1 patient during treatment. Overall, systemic rIFN therapy was well tolerated; its long-term administration in patients with AIDS-associated mucocutaneous KS seems to be well justified according to these preliminary observations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Combination therapy with interferon alfa 2a and PUVA in cutaneous T-cell lymphoma]

Eleven patients with cutaneous T-cell lymphoma stages Ib-IV a were treated with a combination of interferon alfa-2a and photochemotherapy. The diagnosis was confirmed by histological and immunohistological investigations. During the initial treatment, interferon alfa-2a was given at a maximum dose of 9 million IU 3 times a week. Few patients received for a short time 9 million IU daily s.c. The total dose amounted to an average of 125 million IU. Simultaneously, photochemotherapy with a maximum single dose of 2 J/cm2 was applied. The total dose ranged between 7 and 62.9 J/cm2, which corresponds to an average dose of 22.6 J/cm2. After achieving a complete or partial remission the dose of interferon was reduced to 1.5 or 3 million IU, which was then maintained for long-term treatment 2 or 3 times a week. Photochemotherapy was given twice weekly for a minimum of 2 months and then stopped, depending on the course of the disease. The success of therapy was judged from the clinical and histological picture. The combination treatment was well tolerated and led to complete remission in 5 patients (45%) and a partial remission in 6 patients (55%) after the initial therapy which lasted for an average of 48 days. During the follow-up period, which now amounts to 2-13 months with under 1.5 or 3 million IU interferon, three patients have shown disease progression. One patient responded well to newly applied photochemotherapy and in two patients local tumors regressed after radiation.     

Kaposi's sarcoma and its management by radiotherapy

Thirteen patients with Kaposi's sarcoma were treated by radiotherapy between 1975 and 1984. Five patients were kidney transplant recipients receiving immunosuppressive drugs, while eight patients had spontaneous Kaposi's sarcoma. Eleven patients were followed up for periods from two to 63 months (mean, 27 months). All patients had complete response throughout the period of follow-up except one patient who developed recurrence one year after completion of radiotherapy. There was no difference in the response between transplant recipients and patients with spontaneous disease. This response was also unrelated to the dose or type of radiation used. Radiotherapy has been found effective in the local control of Kaposi's sarcoma with complete relief of symptoms and minimal morbidity.     

Interferons in dermatology

Interferons are a large family of proteins and glycoproteins, naturally occurring or artificially produced by recombinant biotechnology. Their antiviral, antiproliferative, antitumoral, and immunomodulatory activities are induced by alterations in cell metabolism after binding to specific membrane receptors. Interferons have been used for the treatment of viral papillomas (e.g., verruca vulgaris and condyloma acuminatum), human immunodeficiency virus (HIV)-associated Kaposi's sarcoma and cutaneous tumors (e.g., melanoma, cutaneous T cell lymphoma, and basal cell carcinoma), and inflammatory dermatoses (e.g., Beh?et's syndrome and psoriatic arthropathy). Clinical trials have been performed worldwide with various regimens and have not always led to conclusive results. In our experience long-term therapy with high doses of subcutaneously injected, recombinant interferon-alpha-2a in patients with HIV-associated Kaposi's sarcoma induces a remission or stabilization of the disease. In malignant melanoma a low response rate is obtained in metastatic disease with the use of interferon as a single therapeutic agent. Combined with other antitumor agents, however, interferon seems to be a useful drug. Excellent control of Beh?et's disease has been obtained, and the treatment of condylomata acuminata has been effective.     

Granulocyte colony stimulating factor (G-CSF) in treatment of patients with HIV-associated mucocutaneous Kaposi sarcoma. Successful use in virus and drug-induced leukopenia]

Three patients with HIV-associated Kaposi sarcoma were treated with human recombinant granulocyte colony stimulating factor (G-CSF). They had all developed leucopenia during treatment with recombinant interferon-alpha-2a, in two cases combined with vincristine. In all three patients, there was an obvious rapid stimulation after s.c. injection of 300 or 150 micrograms G-CSF per day; the white blood count reached normal values within only a few days and partial transformation to leucocytosis took place. After discontinuation of G-CSF, leucocyte counts regressed rapidly to pretreatment levels. A dose of 150 micrograms of G-CSF twice to three times per week proved to be sufficient to keep the white blood cell count in the normal range allowing the treatment necessary for Kaposi sarcoma. G-CSF therapy had no serious side effects. One of the patients developed a tumour-like infiltration in his left upper jaw, which histologically simulated Burkitt's lymphoma and which regressed spontaneously after discontinuation of the G-CSF therapy. G-CSF plays an important role in the treatment of patients with HIV-associated Kaposi sarcoma and enables combined treatment with zidovudine, interferon, and cytostatic drugs.