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PubMed2000

Survey of patients after discontinuing venom immunotherapy.

BACKGROUND: Venom immunotherapy rapidly reduces the risk of a systemic sting reaction in adults from 30% to 70% to less than 2%. When venom immunotherapy is stopped after 5 years or longer, the risk of a systemic sting reaction is 5% to 15% during the first few years after stopping treatment. It is uncertain whether systemic sting reactions will occur more than 5 years after discontinuing venom immunotherapy and whether treatment can be safely stopped in some patients after less than 5 years. OBJECTIVE: The purpose of this study is to estimate the risk of systemic reaction to a sting 10 years after discontinuing treatment and the relative risk after 3 years of treatment compared with that after 5 years or more of treatment. METHODS: Among all patients who had venom immunotherapy at our center, we identified 395 patients who stopped treatment: some had dropped out of therapy early (6-24 months), some stopped after 3 to 4 years, and most completed 5 years or more of venom immunotherapy and were advised to stop by the allergist (many as part of our reported studies of discontinuing venom immunotherapy). RESULTS: Contact was made with 194 patients, including telephone interviews for sting history and requests to visit the office for skin testing and blood sampling. Of these patients, 74 had been included in our original study of patients who had 5 years or more of venom immunotherapy and had sting challenges after 1 to 5 years off venom immunotherapy, as previously reported. Of the 74 in that original study, 61 were reached for this survey, and 30 reported recent stings, with 5 systemic sting reactions. Another 133 patients who had stopped venom immunotherapy were reached: 82 had 5 or more years of venom immunotherapy, 20 had 3 to 4 years of venom immunotherapy, and 31 had less than 2 years of venom immunotherapy. Of 51 patients stung from this group, 27 had 5 or more years of venom immunotherapy (no systemic sting reactions), and 24 had less than 5 years of venom immunotherapy (3 systemic sting reactions). We have now observed a total of 113 patients who had 5 or more years of venom immunotherapy and were stung after stopping. Sixteen (14%) had systemic sting reactions; most were mild, but 4 were severe. Systemic sting reactions occurred in 12 (10.7%) of 112 patients stung in the first 4 years off venom immunotherapy and 5 (10%) of 50 stung more than 5 years off venom immunotherapy. In 4 of 8 patients with current systemic sting reactions, the skin test response was negative, although the venom-IgE response was positive at the previous encounter. All systemic sting reactions were similar in pattern and severity to prevenom immunotherapy reactions in the same patient. CONCLUSIONS: We conclude that the risk of systemic sting reactions when venom immunotherapy is stopped after 5 years or longer remains in the reported range of 5% to 15% in the 5 to 10 years after stopping venom immunotherapy. This risk of systemic sting reactions does not seem to decrease over time, unlike the progressive decline in immunologic markers (skin test and venom-IgE responses). To prospectively assess the risk of recurrent systemic sting reactions, there is a need for sting challenge studies of patients who have been off venom immunotherapy for 5 to 10 years and patients who have stopped venom immunotherapy after just 3 to 4 years treatment.

Adult↗
PubMedDate not supplied

[Preventive immunotherapy].

Allergen specific immunotherapy has been shown to be effective in rigorous double-blind placebo-controlled clinical trials in both children and adults A recent WHO position paper stated that immunotherapy is an effective treatment for patients with allergic rhinitis/conjunctivitis, allergic asthma and allergic reactions from stinging insects and is thought to be more effective in children than in adults. When speaking about children there are several questions that are important regarding the natural course of the disease. One of the most important is whether immunotherapy can prevent asthma, either by preventing sensitisation to allergens related to the development of asthma or by preventing the inflammation in the lungs caused by allergen exposure. Another point could be to establish the differences in the long term outcome of those patients treated with immunotherapy and medication during childhood, compared to the long term outcome of those with comparable asthma features who received only antiasthmatic medication The PAT study is a European multi-center study. The end-point is to show in what capacity allergen specific subcutaneous immunotherapy can prevent the development of asthma in children who only have rhinoconjunctivitis secondary to grass or birch pollen sensitisation. Two hundred and ten children aged from 5 to 13 years were included in the study. Children were randomised to the active treatment group receiving allergen specific immunotherapy with birch and/or timothy pollen allergen extract or to the control group receiving only pharmacotherapy. It is important to highlight that the main criteria to be included was that the children should never have had any asthmatic symptom. Immunotherapy has been effective in terms of decreasing significantly the amount of symptoms in the active group compared to the control one. It was safe with no serious adverse reactions and reduced the risk of the onset of asthma. After two years of treatment more children in the control group developed clinical asthma than in the active group: p = 0.004. Des Roches et al reported the results of a prospective non randomised trial of immunotherapy with Dermatophagoides pteronyssinus in 44 asthmatic children younger than six years of age who were sensitive only to dust mites. The purpose of the study was to assess whether immunotherapy could reduce the development of new sensitisation during a period of three years of follow up. Specific immunotherapy was given with only D. Pteronyssinus extract. All 22 children in the control group developed new sensitivities as determined by skin testing and in vitro tests, while 10 (45%) of 22 children who received mite immunotherapy did not develop additional sensitivities. The findings of this study suggests that immunotherapy may alter the natural course of the allergic sensitisation reducing the risk of developing new sensitisation in mono sensitive children. A limited number of studies have examined the long terms effects of immunotherapy on the clinical presentation of asthma and rhinoconjunctivitis, and have shown a long lasting efficacy decreasing the amount of symptoms 6-10 years after termination. In a retrospective study of children treated with immunotherapy during childhood for at least three years, that were re-evaluated in early adulthood, the control patients who were treated with medication and no immunotherapy suffered almost 3.5 times more symptoms than the active group treated with immunotherapy. The current findings suggest that immunotherapy should be considered earlier in the course of allergic disease to prevent progression or to prevent the development of new sensitisation. Further studies with long term follow up particularly in children could address this possibility.

Adolescent↗
PubMed2006

The effects of grass pollen allergoid immunotherapy on clinical and immunological parameters in children with allergic rhinitis.

Allergoid immunotherapy is a new form of allergen immunotherapy allowing safe administration of high allergen doses. There is limited information on the effects of allergoid immunotherapy in children with allergic rhinitis. To investigate the immunological and clinical effects of allergoid immunotherapy in children with allergic rhinitis due to grass pollen allergy. Children with allergic rhinitis were assigned to allergoid immunotherapy (n = 27) or control (n = 26, no immunotherapy) groups. Children in the immunotherapy group received seven injections of grass pollen allergoid immunotherapy before grass pollen season and continued to receive maintenance immunotherapy for 27 months. All patients were offered a pharmacotherapy regimen to be used on demand during the pollen seasons. Clinical and laboratory parameters were compared between the immunotherapy and control groups. The rhinoconjunctivitis symptom-medication score and asthma symptom score were lower in the immunotherapy group after 1 yr of maintenance immunotherapy (p < 0.01 for both). Skin test reactivity and nasal reactivity as determined by nasal provocation testing for grass pollen were significantly decreased after 1 yr of immunotherapy (p < 0.001 for both). The seasonal increase in bronchial reactivity and nasal lavage eosinophil cationic protein levels were prevented after the first year of immunotherapy (p < 0.05 for both). The seasonal increase in immunoglobulin (Ig)E decreased (p < 0.05) and grass-specific IgG, IgG(1) and IgG(4) increased significantly already at the end of the seven-injection build-up therapy (p < 0.001, for all). Interleukin (IL)-4 levels in the culture supernatants showed a steady decline from baseline at first and second year of immunotherapy (p < 0.001) but remained unchanged in the control group. Allergoid immunotherapy is an effective method in the treatment of grass pollen-induced allergic rhinitis in children and prevents the seasonal increase in bronchial hyper-reactivity. Changes in specific IgE and IgG levels and decreased IL-4 production in peripheral blood mononuclear cell culture supernatants may account for the observed clinical effects.

Adolescent↗
PubMedDate not supplied

[New administration routes for immunotherapy].

Specific immunotherapy represents the turning point of the treatment of allergic illnesses and this, together with avoiding the allergen, currently constitutes the only etiologic treatment available. When conditions are optimum, which include showing the etiologic importance of the allergen, the availability of quality allergenic extracts and the correct monitoring of the patient, immunotherapy with subcutaneous injections is a safe and efficient treatment. As in any other treatment, subcutaneous immunotherapy is not exempt from possible adverse reactions related to its administration, although when the recommended guidelines are followed, these reactions tend to be predominantly local, of little intensity and easy to control. Over the last 15 years, especially in Europe, there has been an increased interest in the use of local applications, not injections, in immunotherapy and we are looking, above all, to increase the safety and the patients acceptance. The alternative applications to injected immunotherapy that have been studied and used to date are: oral, sublingual, nasal and bronchial. In the World Health Organisation position papers (WHO), from the European Academy of Allergies and Clinical Immunology (EAACI) and the European Society of Paediatric Allergy and Clinical Immunology (ESPACI), bronchial immunotherapy is not recommended, due to the fact that its efficiency is not sufficiently documented and the there is a risk involved with severe side effects of an asthmatic nature. Nasal immunotherapy is not considered to be suitable for clinical use on children and oral immunotherapy is not considered to be suitable for clinical use on children and oral immunotherapy is not recommended, except as part of controlled studies, due to the risk of side effects and insufficient documentation that guarantees the efficiency. Currently, in clinical practice, it apears that a progressive interest has been detected in sublingual immunotherapy and in our country this is being used more and more, which means that the current level of our knowledge on this terapeutical method should be reviewed. In order to consider sublingual immunotherapy as a valid alternative, taking the bassis of its action mechanisms as a starting point, a greater safety in its administration should be checked, its clinical efficiency demonstrated and this efficiency should at least be comparable to that obtained using subcutaneous immunotherapy. The action mechanism of sublingual immunotherapy is unknown. Experiments using allergenic extracts marked with radioactive isotopes administered sublingually do not indicate any absorption through the oral mucous, which is reassuring in the sense that no systematic adverse reactions are feared, but on the other hand we are faced with serious doubts concerning the basis for this type of immunotherapy administration. Sublingual immunotherapy, especially when the treatment is exclusively sublingual (where the dose is subsequently spat out), is a safe treatment according to what can be deduced from the clinical tests and the pharmacovigilance studies published, although the sublingual means of administration with a subsequent ingestion of the dose can give rise to adverse systematic reactions, such as urticaria and asthma. From the experience gained since this method has been used, to date there have been no reported serious systematic reactions that are life threatening. The analysis of the results of the double-blind control clinical tests published to date, lead us to the same conclusion as the WHO, the EAACI and the ESPACI position papers, in the sense that there is not sufficient evidence available to recommend the use of sublingual immunotherapy on children, except when it is part of a controlled study. (ABSTRACT TRUNCATED)

Administration, Intranasal↗
PubMed1997

Discontinuation of yellow jacket venom immunotherapy: follow-up of 75 patients by means of deliberate sting challenge.

BACKGROUND: Venom immunotherapy is effective in preventing systemic reactions in patients with a history of an anaphylactic reaction to Hymenoptera stings. It is uncertain how long venom immunotherapy should be continued. OBJECTIVE: We evaluated whether the duration of venom immunotherapy given to yellow jacket-sensitive patients related to the risk of an anaphylactic reaction to a later sting. METHODS: Seventy-five yellow jacket-sensitive patients (29 male and 46 female) received a median number of three in-hospital sting challenges from a live insect in 3 subsequent years after discontinuation of venom immunotherapy. An anaphylactic reaction to one or more of the sting challenges was considered a relapse. We analyzed whether patients with and patients without a relapse differed in terms of gender, age, preimmunotherapy skin test data, preimmunotherapy level of venom-specific IgE, severity of the field-sting reaction that preceded immunotherapy, severity of the reaction to the sting challenge that preceded immunotherapy, adverse reactions to immunotherapy, changes in IgE and IgG4 levels during immunotherapy, duration of immunotherapy, and presence of venom-specific IgE after cessation of therapy. RESULTS: Venom immunotherapy was given for a median duration of 40 months (range, 7 to 120 months). Relapses were observed in six patients. In two of them, a rather severe anaphylactic reaction was observed after the second sting challenge. No relation was found between duration of venom immunotherapy and relapse risk. The relapse rate was higher among patients with high levels of specific IgE before and after immunotherapy. During therapy, the mean level of specific IgE decreased. This decline persisted in the 3 following years. No relapses of sting reactions were observed among patients without detectable specific IgE. CONCLUSION: Discontinuation of venom immunotherapy appears safe for patients with pretreatment IgE antibodies if these antibodies can no longer be detected during immunotherapy. For the remaining patients, a treatment period of 3 years may suffice. After discontinuation of immunotherapy, a clinical sting challenge can be considered to estimate the patient's current grade of hypersensitivity.

Adolescent↗
PubMed1999

Utilization and cost of immunotherapy for allergic asthma and rhinitis.

BACKGROUND: Allergic rhinitis and asthma are important sources of morbidity among adults and children. Although immunotherapy is sometimes used to treat these conditions, there is little information on its use, adherence, or cost in the general population. OBJECTIVE: We sought to characterize the recipients of immunotherapy for allergic rhinitis and/or asthma with respect to their immunotherapy and utilization of health care services. METHODS: A combination of automated and manually extracted data was used to identify HMO members with diagnoses of allergic rhinitis or asthma who were treated with immunotherapy. Costs associated with immunotherapy and related care were examined by linear regression. Proportional hazards and Kaplan-Meier plots were used to evaluate duration of therapy. RESULTS: Of the 122,196 persons with a diagnosis of asthma or rhinitis, 2,667 were also treated with immunotherapy. Eligibility criteria were satisfied by 603 individuals who had 28,266 encounters for immunotherapy (median 48). Most patients (>80) were treated with multiple allergens; ragweed was the most common single allergen administered. Thirty-three percent of patients with sufficient observation time completed the intended course of 61 immunotherapy treatments. Females and younger patients had shorter durations of immunotherapy. The most common reason for discontinuation of therapy was patient's decision (54%). Immunotherapy costs were related most strongly to costs for care of rhinitis and asthma. Prescription drugs accounted for more than 50% of the non-immunotherapy costs; hospitalizations accounted for less than 20%. CONCLUSIONS: Approximately 2% of HMO members with an asthma or rhinitis diagnosis received immunotherapy. Although screened to optimize compliance, most patients did not complete immunotherapy. Costs of non-immunotherapy care were higher for individuals who completed immunotherapy which is consistent with more severe disease in this group.

Adolescent↗
PubMed1998

Allergen-specific immunotherapy for allergic rhinitis: a new insight into its clinical efficacy and mechanism.

Immunotherapy has been used widely for allergic diseases for more than 90 years but, in the opinion of many physicians, it is still a controversial form of treatment. The exact mechanism of action of immunotherapy remains to be determined. In the present study, we review the clinical efficacy and mechanism of action of immunotherapy for allergic rhinitis. Recent double-blind placebo-controlled studies have demonstrated the clinical efficacy of immunotherapy for allergic rhinitis. This therapeutic method has several advantages over conventional pharmacological treatment. Immunotherapy is inferior to pharmacological treatment in the short term, but in the long term it is substantially superior with respect to clinical efficacy. Immunotherapy has the potential permanently to alleviate the abnormal immunological responses of allergic rhinitis and to cure the nasal symptoms in the long term, even after discontinuation of injections. In addition, immunotherapy can prevent the onset of new sensitizations in allergic patients and may prevent the progression of rhinitis to asthma. It may therefore be possible for immunotherapy to alter the natural history of allergic sensitization and its clinical manifestation. These lines of clinical evidence could affect strategies of long-term therapy for allergic rhinitis. Modern molecular biological techniques have suggested that immunotherapy may affect allergen-induced TH responses or cytokine profiles, but there is no general agreement among investigators. However, IL-5 is likely to be the most important cytokine involved in the clinical efficacy of immunotherapy, and the suppression of allergen-induced IL-5 synthesis is most likely to be involved in the mechanism of immunotherapy. Our recent investigations, focusing on specific IgE and IgG4 responses, suggest that immunotherapy-induced changes in these specific antibodies play a clinical role and are involved in the mechanism of action of immunotherapy. It is probable that immunotherapy modulates and affects many different immunological and non-immunological phenomena to produce clinical efficacy and that clinical improvement is a consequence of different mechanisms over time.

Allergens↗
PubMed2003

Allergen-specific conventional immunotherapy decreases immunoglobulin E-mediated basophil histamine releasability.

BACKGROUND: Allergen-specific immunotherapy has proven to be clinically effective in the treatment of patients with atopic asthma; however, the mechanisms are still unclear. Several noted immunological changes include an increase of the allergen-specific IgG antibody, a reduction in the allergen-specific IgE antibody subsequent to transient increase, an allergen-specific T cell shift in cytokine production from Th2 to Th1, and a decrease in quantity and activity of basophils and mast cells. OBJECTIVE: To analyse the changes of basophil histamine release in response to IgE-mediated and non-IgE-mediated stimuli before and after conventional house-dust mite immunotherapy in children who suffer from atopic asthma. METHODS: Fourteen Dermatophagoides farinae (Df) sensitive asthmatic children with conventional immunotherapy were examined. Basophil histamine releasability was measured 0 months (just before immunotherapy), 4 months and 9 months after immunotherapy. Basophils were stimulated with Df and goat anti-human IgE antibody as IgE-mediated stimuli; and formyl-Met-Leu-Phe (fMLP) and calcium ionophore A23187 as non-IgE-mediated stimuli. Accordingly, the asthma symptom score was used to assess clinical outcome and the skin test reactivity to Df was measured. RESULTS: In contrast to pre-immunotherapy activity, 4 and 9 months after immunotherapy there were significant decreases in histamine release by Df and by anti-IgE antibody. The histamine release by fMLP and by calcium ionophore showed no significant changes after immunotherapy. Histamine release by Df demonstrated significant correlation to that by anti-IgE antibody and by fMLP, yet there was no observable correlation between histamine release by Df and by calcium ionophore. The asthma symptom score decreased significantly 4 and 9 months after immunotherapy and showed significant correlation with histamine release by Df. The skin test reactivity (allergen/histamine ratio) remained constant 4 months after immunotherapy, but decreased significantly 9 months after immunotherapy. CONCLUSION: Basophils have the potential to play an important role in the early clinical improvement of conventional immunotherapy in children with atopic asthma, which may be a result of the decreased IgE-mediated histamine releasability during immunotherapy.

Adolescent↗
PubMed1996

Rush immunotherapy: experience with a one-day schedule.

INTRODUCTION: Rush immunotherapy is a method for rapidly desensitizing patients to inhalant allergens. The frequency of systemic reactions during rush immunotherapy is similar to conventional immunotherapy when premedication is used. The most rapid protocol for rush immunotherapy reported to date requires one and one-half days which is inconvenient to patients and clinic schedules. To improve this situation and decrease the cost of giving rush immunotherapy, we have developed a 1-day protocol. METHODS: for this ongoing study, 22 allergic patients received rush immunotherapy consisting of eight injections over six hours followed by two hours of observation in an outpatient clinic. Five had rhinitis and the rest has asthma, seven of whom were steroid-dependent. All were premedicated with astemizole, ranitidine, and prednisone for three days including the day of rush immunotherapy, and peak expiratory low rates were monitored. RESULTS: Systemic reactions were seen in five of 22 (23%). They occurred following the sixth injection (1), seventh injection (2), or the final one (2) and consisted primarily of rhinitis or pulmonary symptoms with one episode of mild anaphylaxis. A systemic reaction was seen in only one steroid-dependent asthmatic patient. A local reaction preceded a systemic reaction in only one patient. All but three reached a maintenance dose in one day. All systemic reactions responded to epinephrine and all patients could go home after rush immunotherapy. Only one patient had a systemic reaction during the three months after rush immunotherapy. CONCLUSION: One day rush immunotherapy is tolerated by most patients with a systemic reaction rate comparable to conventional immunotherapy. All patients were able to reach a maintenance dose months sooner than weekly schedules. With refinement of this procedure, rush immunotherapy may become a widely used method for desensitizing patients with inhalant allergens, and could make immunotherapy less expensive and more convenient.

Adolescent↗
PubMed1998

A comparative study of the clinical efficacy of immunotherapy and conventional pharmacological treatment for patients with perennial allergic rhinitis.

This study was designed to compare the clinical outcome of prolonged immunotherapy for perennial allergic rhinitis with that of pharmacological treatment. Patients with perennial allergic rhinitis due to Dermatophagoides farinae (D. farinae) were divided into two groups; a pharmacotherapy group and an immunotherapy group. The pharmacotherapy group was treated with conventional pharmacological treatment using antihistamine tablets and topical steroid sprays and the immunotherapy group was treated with D. farinae extracts for 5 successive years. None of symptom scores at enrollment differed significantly between the groups. At 6 months and 1 year after the start of treatment the rate of decrease in each score was significantly greater in the pharmacotherapy group than in the immunotherapy group. The rate of decrease in sneezing scores, but not in the other scores, at 2 years after the start of treatment was also greater in the pharmacotherapy group than in the immunotherapy group. However, at 3 years the rate of decrease in any of the scores did not differ significantly between groups. The differences between the groups became clear-cut again after 5 years of treatment, when the rate of decrease in all of the scores was significantly greater in the immunotherapy group than in the pharmacotherapy group. Therefore, short-term treatment with pharmacological agents is probably superior to immunotherapy but, in the long-term, immunotherapy is apparently superior to pharmacological treatment with respect to clinical efficacy. In addition, prolonged immunotherapy provided long-term clinical efficacy and might provide a long-standing cure even after discontinuation of the therapy. In a questionnaire interview, approximately half of patients were very satisfied with prolonged immunotherapy and three-quarters were fairly satisfied or more. Additionally, the magnitude of improvement in nasal stuffiness contributed significantly and exclusively to the patient evaluation of immunotherapy. We propose that prolonged immunotherapy is never inferior to anti-allergenic pharmacological treatment and that it is possible to achieve long-term clinical efficacy or long-standing cure even after the discontinuation of immunotherapy, and that patients with perennial allergic rhinitis will be very satisfied with this prolonged therapeutic technique if nasal stuffiness is considerably alleviated.

Adolescent↗
PubMed2004

Breast cancer immunotherapy.

Breast cancer is a leading cause of cancer-related deaths in women worldwide. Although tumorectomy, radiotherapy, chemotherapy and hormone replacement therapy have been used for the treatment of breast cancer, there is no effective therapy for patients with invasive and metastatic breast cancer. Immunotherapy may be proved effective in treating patients with advanced breast cancer. Breast cancer immunotherapy includes antibody based immunotherapy, cancer vaccine immunotherapy, adoptive T cell transfer immunotherapy and T cell receptor gene transfer immunotherapy. Antibody based immunotherapy such as the monoclonal antibody against HER-2/neu (trastuzumab) is successfully used in the treatment of breast cancer patients with over-expressed HER-2/neu, however, HER-2/neu is over-expressed only in 25-30% of breast cancer patients. Cancer vaccine immunotherapy is a promising method to treat cancer patients. Cancer vaccines can be used to induce specific anti-tumor immunity in breast cancer patients, but cannot induce objective tumor regression. Adoptive T cell transfer immunotherapy is an effective method in the treatment of melanoma patients. Recent advances in anti-tumor T cell generation ex vivo and limited clinical trial data have made the feasibility of adoptive T cell transfer immunotherapy in the treatment of breast cancer patients. T cell receptor gene transfer can redirect the specificity of T cells. Chimeric receptor, scFv(anti-HER-2/neu)/zeta receptor, was successfully used to redirect cytotoxic T lymphocyte hybridoma cells to obtain anti-HER-2/neu positive tumor cells, suggesting the feasibility of treatment of breast cancer patients with T cell receptor gene transfer immunotherapy. Clinical trials will approve that immunotherapy is an effective method to cure breast cancer disease in the near future.

Adoptive Transfer↗
PubMed1998

Clinical role of soluble adhesion molecules during immunotherapy for perennial allergic rhinitis.

BACKGROUND: Soluble forms of intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) have recently been identified in serum samples from atopic patients, but their clinical significance in the treatment of allergic diseases remains to be established. OBJECTIVE: To study the clinical roles of serum sICAM-1 and sVCAM-1 during immunotherapy for perennial allergic rhinitis. DESIGN: Our study included 30 nonatopic volunteers and 60 patients with perennial allergic rhinitis due to Dermatophagoides farinae. The 60 patients had been treated for variable periods (7.3+/-3.0 years [mean+/-SD]) with immunotherapy using a standardized D. farinae antigen. Serum samples were collected from each patient before and after immunotherapy to determine sICAM-1 and sVCAM-1 with sandwich enzyme-linked immunosorbent assays. RESULTS: Serum levels of sICAM-1 in the patients before immunotherapy were higher than those in the nonatopic volunteers (P<.001). The levels of sICAM-1 in the patients' serum samples were decreased significantly after immunotherapy (P<.001), and the percentage of the decrease in the sICAM-1 levels was significantly correlated with the duration of immunotherapy (P=.04) and with the percentage of the decrease in symptom scores (P<.001). The levels of sVCAM-1 in the serum samples from the patients with severe symptoms were significantly higher before immunotherapy than those in the nonatopic volunteers (P=.002) and were significantly decreased after immunotherapy (P=.05). However, the percentage of the decrease in the sVCAM-1 levels was not correlated with the duration of immunotherapy (P=.89) or with the percentage of the decrease in symptom scores (P=.89). CONCLUSION: Decrease in serum sICAM-1 levels during immunotherapy is probably involved in the working mechanisms of immunotherapy, but modulation of serum sVCAM-1 levels is not likely related to the clinical effect of immunotherapy.

Adult↗
PubMed2006

Immunotherapy with dendritic cells and CpG oligonucleotides can be combined with chemotherapy without loss of efficacy in a mouse model of colon cancer.

Although immunotherapy has shown promising results in the treatment of cancer, clinical studies assessing immunologic approaches in patients with advanced cancer will seldom be conducted in the absence of conventional treatment strategies such as chemotherapy. Here we investigate the combination of chemotherapy with CpG oligonucleotide and dendritic cell-based immunotherapy in the C26 mouse model of colon carcinoma. The coinjection of antigen-pulsed, mature dendritic cells and CpG oligonucleotides together with a peritumoral injection of CpG oligonucleotides elicits a CD8 T-cell response resulting in tumor rejection and long-term protection in the C26 model. Tumor-bearing mice were treated weekly for 4 weeks by this immunotherapy protocol, by 5-fluorouracil plus leucovorin or irinotecan, or by the combination of immunotherapy and chemotherapy. We observed that immunotherapy was more effective in reducing tumor growth and increasing survival than 5-fluorouracil or irinotecan. Immunotherapy was well tolerated, whereas therapeutic doses of 5-fluorouracil or irinotecan were associated with dose-limiting toxicity. Furthermore, the efficacy of immunotherapy combined with either 5-fluorouracil or irinotecan was similar to that of immunotherapy alone. Addition of immunotherapy to either 5-fluorouracil or irinotecan treatment strongly decreased the toxicity of chemotherapy. Immunotherapy both with and without chemotherapy generated a memory immune response, leading to tumor rejection in mice rechallenged with C26 tumor cells up to several months after treatment. In summary, immunotherapy with a combination of dendritic cells and CpG oligonucleotides is superior to chemotherapy in the C26 tumor model. This immunotherapy protocol can be combined with current chemotherapy agents with no loss in therapeutic activity.

Animals↗
PubMedDate not supplied

[Evaluation of the pediatric aspects of the WHO document and meta-analysis of immunotherapy].

In spite of the existence of numerous scientific studies on the beneficial effect of immunotherapy with specific allergens in the treatment of allergic diseases, their results have not been easily accepted as the methodology and the valuation of the studies have been very heterogeneous. Over the last few years the meta-analysis technology has been developed as a useful tool to globally value the results on the different research studies related to a specific problem. When meta-analyse are carried out correctly, they are accepted as an optimum way to express the results obtained from the different studies from a common view point. In 1995 Abramson MJ, Puy RM and Weiner INI published the first meta-analysis on the efficiency of immunotherapy with specific allergens in the treatment of asthma. The same authors continued to carry out systematic reviews of this theme, and their results were published in the Cochrane Library Document. In october 1999 the latest meta-analysis on immunotherapy in asthma, also carried out by Abramson et al was published in Allergy. In this study 62 investigations published from 1954 to 1998 were included. None of the meta-analyses published to date have separately analysed the studies carried out on children, nor have special considerations been made with respect to the 105 patients who were of paediatric age. The first meta-analysis studies, as well as the ones carried out in 1999, only value random clinical tests, in which there is a valuation of the evolution of asthma and in which mite, pollen, animal, fungi or epithelial allergenic vaccinations are used. Only the subcutaneous administration of the vaccine was allowed. Although this meta-analysis has not been designed to obtain specific conclusions of the effectiveness of immunotherapy in children, probably of conclusions of some of the sections can be applied to the children and/or adolescent population. The authors point out, by valuing the results of the effect of immunotherapy on the clinical evolution, that the studies carried out on children were more homogenous than on adults, which means that their significance on this population is more important. Approximately 50% of the studies that evaluate the clinical evolution, the medicines taken and the specific BHR study with allergens, included children and/or adolescents. It is very probable that these conclusions can be applied to the population between 5 and 18 years old that suffer from allergic asthma, but it is clear that a meta-analysis of the efficiency of immunotherapy in paediatrics is needed. Recently regulations on immunotherapy have been published that appeared after the immunotherapy experts from the World Health Organisation met in Geneva in 1997 (1). The recommendations for immunotherapy in children are clear and similar to those applied to adults: 1. Rhonoconjunctivitis and allergic asthma mediated by IgE. 2. Serious anaphylactic reactions caused by hymenoptera bites. 3. The same diagnosis and treatment considerations recommended are applied to children as well as adults. It is not indicated for allergies to food substances and atopic dermatitis. The patients age is another factor to be considered and, except in the case of allergy to hymenoptera poison, when the patient is under 5 it is a relative counter indication to administer immunotherapy. In general it is admitted that immunotherapy is more efficient on children than on adults, but more studies need to be carried out on the efficiency and safety on children under 5. The early treatment with immunotherapy in children who suffer from allergic respiratory illnesses can have an important significance, as this type of treatment could have a preventive nature as it prevents the rhinitis developing into asthma, as well as the beneficial effect that has been shown on children with allergic asthma.

Adolescent↗
PubMed2005

Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis.

BACKGROUND: Rush immunotherapy (RIT) presents an attractive alternative to standard immunotherapy. However, RIT carries a much greater risk of acute allergic reactions, including anaphylaxis. OBJECTIVES: We hypothesized that omalizumab, a humanized monoclonal anti-IgE antibody, would be effective in enhancing both safety and efficacy of RIT. METHODS: Adult patients with ragweed allergic rhinitis were enrolled in a 3-center, 4-arm, double-blind, parallel-group, placebo-controlled trial. Patients received either 9 weeks of omalizumab (0.016 mg/kg/IgE [IU/mL]/mo) or placebo, followed by 1-day rush (maximal dose 1.2-4.0 mug Amb a 1) or placebo immunotherapy, then 12 weeks of omalizumab or placebo plus immunotherapy. RESULTS: Of the 159 patients enrolled, 123 completed all treatments. Ragweed-specific IgG levels increased >11-fold in immunotherapy patients, and free IgE levels declined >10-fold in omalizumab patients. Patients receiving omalizumab plus immunotherapy had fewer adverse events than those receiving immunotherapy alone. Post hoc analysis of groups receiving immunotherapy demonstrated that addition of omalizumab resulted in a 5-fold decrease in risk of anaphylaxis caused by RIT (odds ratio, 0.17; P = .026). On an intent-to-treat basis, patients receiving both omalizumab and immunotherapy showed a significant improvement in severity scores during the ragweed season compared with those receiving immunotherapy alone (0.69 vs 0.86; P = .044). CONCLUSION: Omalizumab pretreatment enhances the safety of RIT for ragweed allergic rhinitis. Furthermore, combined therapy with omalizumab and allergen immunotherapy may be an effective strategy to permit more rapid and higher doses of allergen immunotherapy to be given more safely and with greater efficacy to patients with allergic diseases.

Adolescent↗
PubMed1996

Serum levels of soluble interleukin-2 receptor in patients with perennial allergic rhinitis before and after immunotherapy.

BACKGROUND: Interleukin-2 receptor (IL-2R) exists in soluble form in sera, and the rate of release of the soluble form of IL-2R (soluble IL-2R) reflects T cell activation in vivo. Since T lymphocytes play a central role in respiratory allergic disorders, the measurement of serum levels of soluble IL-2R may be useful in analyzing the disease state of allergic disorders. OBJECTIVE: To investigate the serum concentrations of soluble IL-2R in 48 patients with perennial allergic rhinitis and 14 nonatopic healthy controls, with special reference to the possible changes following long-term immunotherapy. METHODS: This retrospective study included 48 patients who had had variable periods of long-term immunotherapy with Dermatophagoides farinae extracts. The duration of immunotherapy ranged from 5 to 15 years. Serum samples were collected twice from each patient, before the initiation of immunotherapy and at the time of clinical assessment of immunotherapy. All the serum samples were simultaneously used for determination of soluble IL-2R concentrations, by the use of an enzyme-linked immunosorbent assay. To serve as controls, 14 nonallergic subjects of the same age range and sex were chosen. RESULTS: Patients with allergic rhinitis before immunotherapy had significantly higher serum levels of soluble IL-2R than nonatopic subjects. Elevated serum levels of soluble IL-2R decreased significantly following immunotherapy and the serum levels of soluble IL-2R in patients with allergic rhinitis after immunotherapy were not statistically different from those of nonatopic subjects. In addition, the percent decrease in serum soluble IL-2R correlated significantly with the duration of immunotherapy. CONCLUSIONS: Hyperactivity of helper T cells of atopic patients is altered after long-term immunotherapy, and such immunoregulatory changes could be theoretically involved in the mechanisms of immunotherapy.

Adolescent↗
PubMed1997

Immunotherapy affects the seasonal increase in specific IgE and interleukin-4 in serum of patients with seasonal allergic rhinitis.

This study was designed to determine seasonal changes in cytokines, soluble CD23 and specific IgE in the serum of patients with seasonal allergic rhinitis, and the effect of immunotherapy on these seasonal changes. Fifty-four patients with seasonal allergic rhinitis caused by Japanese ceder pollens were divided into a medication group and an immunotherapy group. The patients of the medication group were treated with non-sedating antihistamines alone during the pollen season. The patients of the immunotherapy group had been treated for variable periods (mean, 5.0 +/- 3.2 years) with immunotherapy using japanese cedar pollen antigens. Serum samples were collected before and during the pollen season from each patient, to determine specific IgE, interleukin-4 (IL-4), interferon-gamma (IFN-gamma) and soluble CD23 levels in serum. A significant increase in specific IgE and IL-4 and a significant decrease in IFN-gamma were observed during the pollen season in the medication group. In contrast, in the immunotherapy group, none of specific IgE, IL-4 and IFN-gamma was significantly changed following natural exposure to pollens. However, these effects were not significant in patients undergoing immunotherapy for 3 or fewer years. Seasonal rates of increase in specific IgE and IL-4 differed significantly between good responders and poor responders to immunotherapy, but seasonal rates of decrease in IFN-gamma did not. A seasonal rate of increase in soluble CD23 was significantly correlated with a seasonal rate of increase in specific IgE, in both the medication and the immunotherapy groups. The seasonal rate of increase in soluble CD23 was significantly smaller in the good responders than in the poor responders to immunotherapy. In conclusion, pollen immunotherapy reduces the seasonal increase in specific IgE, IL-4 and soluble CD23 in serum, and in addition switches the seasonal preferential activation of Th-2 cells to reciprocal activation of Th-1 cells with treatment over several years. It is likely that the mechanisms responsible for the clinically beneficial effects of immunotherapy principally involve the modulation of Th-2 rather than Th-1 cytokines.

Adult↗
PubMed1979

Immunotherapy of melanoma.

Malignant melanoma is a disease characterized by clinical evidence of host defense, possibly immunologically mediated. It is a disease which tends to be refractory to both radiotherapy and chemotherapy. Immunotherapy has been used in three phases of the disease. 1. Intralesional immunotherapy with a nonspecific immune adjuvant in patients with local intradermal or soft tissue recurrence. This treatment produces approximately 15% regression of both injected and uninjected lesions, and about 60% regression of injected lesions only. Both clinical and laboratory evidence suggests that this regression is immunologically mediated. 2. Patients with surgical removal of all clinically demonstrable tumor, either primary disease alone or regional node recurrence, active nonspecific, and specific, immunotherapy has been used in an adjuvant setting. There is considerable controversy about the benefits accruing to such immunotherapy, but most large scale prospective and randomized studies have suggested that if benefit does result it is modest in degree and probably cannot be measured in terms of increase in cure rate. 3. Immunotherapy has also been used as a nonspecific active adjuvant to single drug or polychemotherapy in patients with disseminated melanoma. Whereas complete response rate may be slightly increased by this maneuver there is no convincing evidence that immunotherapy markedly increases the total objective response rate to polychemotherapy, and survival is only marginally superior when immunotherapy is added to chemotherapy in this setting. Further studies need to be done with active specific immunotherapy with tumor cell membrane extracts; as an adjuvant in patients with minimal body burden of tumor cells; and to study the inaction between chemotherapy and immunotherapy in this disease. Furthermore, studies of chemically defined fractions of either bacterial cell wall or tumor cell extracts must be evaluated both in terms of their ability to augment cell mediated immune responses in the melanoma patient, and also in terms of their ability to induce objective benefit for the patient. The possible use of immunotherapy in patients with primary melanoma has been briefly explored but needs further study. Possible additive effects with radiotherapy and immunotherapy should also be looked at in this disease utilizing high dose fractions and other new forms of radiotherapeutic technique.

Adjuvants, Immunologic↗