RESUMO
An apheresis registry is a part of each learned apheresis society. The interest in this is obvious, in terms of knowledge of the practice of apheresis, adverse events, and technical issues. However, because of the weight of data entry it could never be exhaustive and some data will be missing. While continuing our registry efforts and our efforts to match with other existing registries, we decided to extend the data collection to a medico-economic database that is available in France, the Programme de Médicalisation du Système d'Information (PMSI) that has covered reimbursement information for each public or private hospital since 2007. It contains almost all apheresis procedures in all apheresis fields, demographic patient data, and primary and related diagnoses, among other data. Although this data does not include technical apheresis issues or other complications of the procedures, its interest is great and it is complementary to the registry. From 2003-2014, we have recorded 250,585 apheresis procedures, for 48,428 patients. We showed that the data are reliable and exhaustive. The information shows a perfect real life practice in apheresis, regarding indications, the rhythm and the duration of apheresis treatment. This prospective data collection is sustainable and allows us to assess the impact of healthcare guidelines. Our objective is to extend the data collection and match it to other existing databases; this will allow us to conduct, for example, a cohort study specifically for ECP.
Assuntos
Remoção de Componentes Sanguíneos/economia , Seguro Saúde/tendências , Remoção de Componentes Sanguíneos/métodos , França , Humanos , Sistema de RegistrosAssuntos
Fotoferese/tendências , Ficusina/uso terapêutico , História do Século XX , História Antiga , Humanos , Tolerância Imunológica , Imunidade Celular , Linfoma Cutâneo de Células T/tratamento farmacológico , Fotoferese/história , Fotoferese/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Síndrome de Sézary/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia , Linfócitos T Reguladores/efeitos dos fármacosRESUMO
DHAP regimen is commonly used in patients with lymphoma. It is routinely used in combination with the monoclonal anti-CD20 antibody rituximab (R-DHAP), particularly for peripheral blood stem cell (PBSC) mobilization. The aim of this study was to assess the impact of rituximab on PBSC mobilization in patients with lymphoma receiving DHAP chemotherapy. We retrospectively reviewed the data of patients treated by DHAP or R-DHAP regimens as PBSC mobilization protocol between July 1998 and June 2005. Sixty-nine patients were included in the study: 21 in the DHAP group and 48 in the R-DHAP group. Both groups were not statistically different in term of clinical and biological presentation of the disease. The first cytapheresis was performed at day 10 in the R-DHAP group versus day 11 in the DHAP group. In contrast, the number of circulating CD34(+) cells was higher, but not significant, in the R-DHAP group than the DHAP group, namely 9.7x10(6) CD34(+) cells/kg and 6.1x10(6) CD34(+) cells/kg, respectively. Finally, the complete remission status at time of harvest was the only one factor associated with poor mobilization on multivariate analysis. In conclusion, our results show that rituximab does not impair PBSC collection.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Antígenos CD20/química , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Linfoma/tratamento farmacológico , Linfoma/terapia , Células-Tronco/metabolismo , Adulto , Idoso , Anticorpos Monoclonais/química , Anticorpos Monoclonais Murinos , Cisplatino/uso terapêutico , Citarabina/uso terapêutico , Dexametasona/uso terapêutico , Feminino , Humanos , Linfoma/mortalidade , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , RituximabRESUMO
Plasma therapy consists in bringing to a patient in need - in general suffering a severe, resistant to current therapy, and even lethal infection - plasma or specific, fractioned, antibodies, along with other immunoglobulins and possibly healing factors that can be obtained from immunized blood donors; donors (voluntary and benevolent) can be either actively immunized individuals or convalescent persons. Plasma therapy has been used since the Spanish flu in 1917-1918, and regularly then when viral epidemics threatened vulnerable populations, the last reported occurrence being the 2013-2015 Ebola virus outbreak in West Africa. The precise action mechanism of plasma therapy is not fully delineated as it may function beyond purified, neutralizing antibodies.
Assuntos
Imunização Passiva/métodos , Infecções/terapia , Plasma , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/sangue , Anticorpos Antivirais/uso terapêutico , Convalescença , Surtos de Doenças , Previsões , Humanos , Imunização Passiva/tendências , Plasma/imunologia , Viroses/epidemiologia , Viroses/terapiaRESUMO
Various studies have reported that primary human immunodeficiency viruses seem to be more refractory to neutralization by HIV-positive sera than T cell line-adapted strains. In this study we also show that adaptation of the HIV-1SF-2 strain, produced in PBMCs, to the cell line CEM-SS renders this isolate sensitive to neutralization by almost all the sera tested. Further neutralization studies should thus focus on the development of an assay involving primary isolates in order to detect antibodies having a neutralizing activity in vivo. Neutralization protocols currently use either an antibody end-point dilution assay, which combines a fixed inoculum of virus with serial dilutions of antibody, or an infectivity reduction assay, which uses serial dilutions of virus with a single dilution of antibody. We have developed an assay designed for studying the neutralization of primary isolates that combines these two approaches. Performing the assay on PBMCs allows all primary isolates to be analyzed, not just those multiplying in T cell lines. The neutralizing titer measured on PBMCs for human HIV-positive sera is low, but reproducible and independent of the virus titer in a given experiment. It can be increased about five-fold by changing the temperature and duration of virus-serum interaction (overnight at 4 degrees C instead of 1 hr at 37 degrees C). These results emphasize the need for a relevant neutralization assay involving primary isolates and primary cells for a better understanding of the role of humoral response in HIV infection.
Assuntos
Anticorpos Anti-HIV/sangue , HIV-1 , Testes de Neutralização/métodos , Sequência de Aminoácidos , Animais , Linfócitos T CD4-Positivos , Células Cultivadas , Clonagem Molecular , Proteína gp120 do Envelope de HIV/genética , Soropositividade para HIV/imunologia , Humanos , Soros Imunes , Leucócitos Mononucleares , Dados de Sequência Molecular , Pan troglodytes , Fragmentos de Peptídeos/genética , RNA Viral/genética , Alinhamento de Sequência , Análise de Sequência de DNA , Replicação ViralRESUMO
A live recombinant canarypox vector expressing HIV-1 gpl20 MN tm/gag/protease LAI (ALVAC-HIV, vCP205) alone or boosted by a p24E-V3 MN synthetic peptide (CLTB-36) was tested in healthy volunteers at low risk for HIV infection for their safety and immunogenicity. Both antigens were well tolerated. ALVAC-HIV (vCP205) induced low levels of neutralizing antibodies against HIV-1 MN in 33% of the volunteers. None of them had detectable neutralizing antibodies against a nonsyncytium-inducing HIV-1 clade B primary isolate (Bx08). After the fourth injection of vCP205, CTL activity was detected in 33% of the volunteers and was directed against Env, Gag, and Pol. This activity was mediated by both CD4+ and CD8+ lymphocytes. On the other hand, the CLTB-36 peptide was poorly immunogenic and induced no neutralizing antibodies or CTLs. Although the ALVAC-HIV (vCP205) and CLTB-36 prime-boost regimen was not optimal, further studies with ALVAC-HIV (vCP205) are warranted because of its clear induction of a cellular immune response and utility as a priming agent for other subunit antigens such as envelope glycoproteins, pseudoparticles, or new peptides.
Assuntos
Vacinas contra a AIDS/efeitos adversos , Vacinas contra a AIDS/imunologia , Avipoxvirus/imunologia , Anticorpos Anti-HIV/biossíntese , HIV-1/imunologia , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/imunologia , Adulto , Sequência de Aminoácidos , Avipoxvirus/genética , Feminino , Vetores Genéticos , Anticorpos Anti-HIV/sangue , Proteína do Núcleo p24 do HIV/química , Proteína do Núcleo p24 do HIV/imunologia , Proteína gp120 do Envelope de HIV/efeitos adversos , Proteína gp120 do Envelope de HIV/química , Proteína gp120 do Envelope de HIV/imunologia , Humanos , Esquemas de Imunização , Imunização Secundária , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Peptídeos/síntese química , Peptídeos/química , Peptídeos/imunologia , Linfócitos T/imunologia , Linfócitos T Citotóxicos/imunologiaRESUMO
BACKGROUND AND METHODS: We investigated extracorporeal photochemotherapy--which consists of the collection of blood mononuclear cells by means of a cell separator, their exposure to ultraviolet A light in the presence of a photoactivatable molecule such as 8-methoxypsoralen, and their intravenous reinjection into the patient--for the treatment of an acute lung rejection episode in a severely infected patient, assuming that its mechanism of action is an immunomodulation rather than an actual immunosuppression. RESULTS: Three weeks after the simultaneous beginning of antiinfectious and extracorporeal photochemotherapy treatments, the patient improved clinically. Acute lung rejection was no longer detectable histologically 4 weeks after the beginning of extracorporeal photochemotherapy. Twenty-two months after the beginning of extracorporeal photochemotherapy (47 months after transplantation), the patient was living a normal life. CONCLUSIONS: We believe this treatment may be considered for further studies not only in acute lung rejection therapy when intensive immunosuppression is contraindicated but also as a means of rejection prevention.
Assuntos
Circulação Extracorpórea , Rejeição de Enxerto/tratamento farmacológico , Transplante de Coração-Pulmão , Hipertensão Pulmonar/cirurgia , Terapia PUVA , Separação Celular , Terapia Combinada , Humanos , Imunossupressores/uso terapêutico , Ativação Linfocitária/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Recidiva , Linfócitos T/efeitos dos fármacosRESUMO
The purification and analysis of IgGs from sera of HIV-1-infected and non infected individuals are reported. The effect of antibodies purified from sera of infected individuals on antigen-induced T cell proliferation was investigated in relation to their possible involvement in an autoimmune reaction in AIDS, in view of the previously unravelled striking peptide similarities between HIV-1 gp120 and the immunoregulatory CD4 and Fas molecules. However, our data do not allow definite conclusions to be drawn. The necessity of purifying antibodies against specific peptides to show their direct effect on T-cell activation is further stressed.
Assuntos
Síndrome da Imunodeficiência Adquirida/imunologia , Infecções por HIV/imunologia , HIV-1 , Imunoglobulina G/imunologia , Autoimunidade , Antígenos CD4/imunologia , Proteína gp120 do Envelope de HIV/imunologia , Soronegatividade para HIV/imunologia , Humanos , Imunoglobulina G/isolamento & purificaçãoRESUMO
Extracorporeal photochemotherapy (ECP) has been shown to be effective in variety of pathologic diseases such as Sezary syndrome, autoimmune diseases, organ graft rejection and graft versus host disease. However, its mechanism of action has remained elusive. Understanding of its mechanisms may be useful to identify the best indications, treatment regimes and to optimize the ECP technique. The first step of the ECP procedure is collection of peripheral mononuclear cells. In this step, several cell environment changes occur. These conditions have been suggested to increase monocyte activation and possibly drive dendritic cell differentiation. The second step of ECP is the cell radiation by UVA in presence of 8-MOP which is presumed to induce cell membrane damage, DNA crosslinking and binding to a variety of cytosolic proteins leading to apoptosis, modification of membrane antigenicity and antigen presenting cell activation. The third step of ECP is the reinfusion of the treated cells to the patient. While it is unclear what exactly occurs in vivo, it is thought that DCs play a critical role by inducing an immunological response against pathogenic cells. The immature DC, activated by ECP, phagocytizes and internalizes the apoptotic cells; processes the antigens and increases the synthesis of class I and II Major Histocompatibility Complex (MHC) molecules. The peptides associated with class II MHC are presented to the CD4+ T helper cells. The final maturation of DC is completed in vivo with the help of these activated T helper cells using a variety of mechanisms including CD40 ligation. Finally, the mature DCs fully loaded with pathogenic T cell peptides migrate to secondary lymphoid organs stimulate the naive CD8+ T cells and induce a cytotoxic response (Th1 immune response) directed against pathogenic clones (tumoral cells of Sezary syndrome). Clinical and haematological improvement after ECP in Sezary syndrome is associated with a shift in Th1/Th2 balance and the increase of Th1 cytokines and IL12. ECP can also down regulate the allo or autoimmune response and induces tolerance by regulatory T cells. The clinical response to ECP in patients with chronic GvHD is associated with increase in NK cells and a shift from DC1 to DC2 and a shift from predominantly Th1 to Th2 immune response. Recruitment and involvement of other immune cells in the mechanism of ECP have been suggested and merit more studies. This immunostimulatory capacity of ECP is the most probable hypothesis of its mechanism but further investigations are necessary to determine the precise players important for this activity.
Assuntos
Fotoferese/métodos , Apoptose , Linfócitos T CD4-Positivos/metabolismo , Antígenos CD40/biossíntese , Linfócitos T CD8-Positivos/metabolismo , Membrana Celular/metabolismo , Reagentes de Ligações Cruzadas/farmacologia , DNA/metabolismo , Células Dendríticas/metabolismo , Regulação para Baixo , Doença Enxerto-Hospedeiro/sangue , Humanos , Leucócitos Mononucleares/metabolismo , Metoxaleno/farmacologia , Modelos Biológicos , Células Th1/metabolismo , Células Th2 , Raios UltravioletaRESUMO
Extracorporeal photochemotherapy (EPC) has been used to treat cutaneous T-cell lymphomas as well as a number of immune-mediated disorders. Seven patients above 50 years of age with refractory rheumatoid arthritis (RA) were treated by EPC. Mononuclear cells were harvested, exposed to ultraviolet A light in the presence of 8-methoxypsoralen, then reinfused into the patient. This procedure was repeated eight times over a three-week period. Improvements in clinical parameters were seen in every case as early as the second week and persisted throughout the duration of EPC. Improvements for more than three months were observed in two patients. C-reactive protein levels declined during the treatment period. No adverse reactions were recorded. The mechanism of action of EPC in RA requires elucidation and a controlled study is needed to confirm the efficacy of this technique.
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Artrite Reumatoide/tratamento farmacológico , Fotoferese , Resultado do Tratamento , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Ancestim (r-MetHuSCF) is available in France for compassionate use in patients who are candidates for high-dose chemotherapy and autologous transplantation, and who failed in previous attempts at mobilization and collection. We report here data from 513 adult patients who benefited from this program, between January 1998 and July 2007. Given with systematic premedication, ancestim was generally well tolerated, although severe but not life-threatening adverse events were reported in 12 individuals. Overall, a graft was obtained or completed for 235 patients (46%). The median number of collected CD34+ cells was 3.00 × 10(6)/kg (range: 0.03-39.50). The target threshold of 2 × 10(6) CD34+ cells/kg was reached in 161 patients (31%). Factors associated with collection were diagnosis of myeloma, no previous autologous transplant, no more than one previous failed attempt and a mobilization regimen including cytotoxic agents. A total of 207 patients (40%) proceeded to high-dose chemotherapy and autologous transplantation. The median time to reach 0.5 × 10(9)/L neutrophils and 20 × 10(9)/L platelets was 12 (6-40) and 13 (0-31) days, respectively. We conclude that a combination of ancestim with filgrastim successfully mobilized CD34+ cells in peripheral blood, and allowed adequate collection in preparation for autologous transplantation in approximately one-third of poorly mobilizing patients.
Assuntos
Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Neoplasias/patologia , Fator de Células-Tronco/análogos & derivados , Adolescente , Adulto , Ensaios de Uso Compassivo , Filgrastim , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Humanos , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/cirurgia , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Fator de Células-Tronco/efeitos adversos , Fator de Células-Tronco/uso terapêutico , Transplante Autólogo , Adulto JovemRESUMO
In order to assess the prognostic value of inhibitory anti-ADAMTS13 antibodies in thrombotic thrombocytopenic purpura (TTP), we performed a multicentre prospective study of 33 adult patients with idiopathic acquired TTP. Patients were treated with high-dose plasma infusion and therapeutic plasma exchange. Patients without (group 1, n = 12) and with (group 2, n = 21) detectable inhibitory anti-ADAMTS13 antibodies were compared for clinical presentation, treatment and outcome. Both groups were comparable for clinical presentation. All patients in group 1 achieved a sustained complete remission within a median of 7 d [95% confidence interval (CI), 4-18], which required a median plasma volume of 235 ml/kg (range, 131-1251). In group 2, 17 patients achieved a durable complete remission within a median of 23 d (95% CI, 11-32) (P = 0.001). Median plasma volume was 718 ml/kg (range, 219-3107) (P = 0.02). In group 2, there was a trend for more episodes of flare-up than in group 1 (13 vs. 3, respectively, P = 0.07). Four patients, all from group 2, died (P = not significant). The relapse rate was comparable between both groups. We suggest that TTP with detectable inhibitory anti-ADAMTS13 antibodies displays a worse prognosis, relative to a delayed platelet count recovery, a higher plasma volume requirement to achieve complete remission, and a trend for more frequent episodes of flare-up.
Assuntos
Proteínas ADAM/imunologia , Autoanticorpos/sangue , Púrpura Trombocitopênica Trombótica/terapia , Proteína ADAMTS13 , Adulto , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Troca Plasmática , Contagem de Plaquetas , Prognóstico , Estudos Prospectivos , Púrpura Trombocitopênica Trombótica/sangue , Púrpura Trombocitopênica Trombótica/imunologia , Recidiva , Indução de Remissão , Resultado do TratamentoRESUMO
Extracorporeal photochemotherapy (ECPC) has been investigated experimentally and in clinical conditions in transplant rejection treatment and prevention. Repeated injections of photochemically modified syngeneic alloreactive T cells prior to transplant significantly delay rejection in a mouse skin graft model as well as in a heterotopic heart transplant model in rats. In the latter, we found this effect to be dependent on 3 main parameters, i.e., treatment intensity (number of injections), schedule (injections before and after transplant), and associated immunosuppression (because there is no detectable effect in animals without immunosuppression). In human beings, ECPC was first used for the treatment of acute rejection episode after heart transplantation. At least 2 studies provided evidence that ECPC is as effective as high dose corticosteroids in controlling moderate acute rejections, and several case reports showed that ECPC could be effective in recurrent and/or steroid resistant rejections. ECPC has also been investigated in an open trial to prevent rejection episodes after heart transplantation in patients at high risk of acute rejection because of human leukocyte antigen (HLA) immunization and/or a second or third transplant and found to be successful. In heart transplant recipients at standard risk of rejection episodes, a small scale randomized trial showed a reduction in both rejection episodes and infections in the ECPC treated vs. the standard group. Beyond these studies and other isolated case reports, several large scale randomized trials in heart, lung, and even kidney transplantations (some of them already ongoing), will enable us to define the role of ECPC in the management of transplant recipients.
Assuntos
Rejeição de Enxerto , Transplante de Coração , Transplante de Pulmão , Fotoquimioterapia , Animais , Transplante de Coração/imunologia , Humanos , Transplante de Pulmão/imunologia , Resultado do TratamentoRESUMO
Extracorporeal photochemotherapy (ECP) consists of collection of mononuclear cells, their irradiation with UV-A light in the presence of a photoactivable molecule--8-methoxy-psoralen (8-MOP) being the most widely used--and their reinjection into a patient. Two technical approaches have been developed. The photopheresis procedure involves four steps: (i) 8-MOP is given to the patient orally, 2 h before collection of white blood cells; (ii) a discontinuous flow cell separator (UVAR, Therakos, West Chester, PA, U.S.A.) is used for cell collection. The final product (740 mL) has a hematocrit of 4.5 +/- 1.7%); (iii) irradiation, performed with the same UVAR apparatus, begins before all the cells are collected, and lasts for 180 min after collection; and (iv) after irradiation, the buffy-coat is reinjected into the patient. We developed a technique summarized as follows: (i) mononuclear cell collection is performed using the Spectra (Cobe, Denver, CO, U.S.A.) cell separator, which provides a highly enriched mononuclear cell concentrate (always > 90% purity), in a small volume < 150 mL, subsequently adjusted to 300 mL for irradiation. Hematocrit of the final product is always < 2%. (ii) Soluble 8-MOP is added to the mononuclear cell concentrate at a final concentration of 200 ng/mL. (iii) Mononuclear cell concentrate is transferred in an EVA plastic bag (Macopharma, Tourcoing, France) to ensure an efficient irradiation with a UV irradiator (Vilber Lourmat, Marne-la-Vallée, France). (iv) After irradiation at 2 J/cm2 (time < 20 min), the cells are reinfused into the patient. Experimental and clinical data suggest that ECP has potential applications in the treatment of connective tissue disorders, such as systemic sclerosis and rheumatoid arthritis. Although encouraging data have been obtained, further clinical trials are warranted to establish the role of this therapy in these indications.
Assuntos
Doenças do Tecido Conjuntivo/terapia , Fotoferese/métodos , Animais , Artrite Reumatoide/terapia , Estudos de Avaliação como Assunto , Humanos , Escleroderma Sistêmico/terapiaRESUMO
Extracorporeal photochemotherapy is a recently developed immunomodulator treatment against heart and lung graft rejection. The recipient's mononuclear cells are screened and irradiated with UV-A in the presence of 8-methoxy-psoralene (8-MOP), then reinjected. We treated 4 patients who had begun to reject their heart and/or lung grafts, with this technique, using one session per week for 4 weeks, followed by one session every 2 weeks for 2 months, then one session per month. In all cases, extracorporeal photochemotherapy appeared to improve the clinical and biological status of these patients. Episodes of rejection which could not be reversed with immunosuppressor treatment alone were controlled.
Assuntos
Rejeição de Enxerto/terapia , Transplante de Coração/efeitos adversos , Transplante de Coração-Pulmão/efeitos adversos , Transplante de Pulmão/efeitos adversos , Fotoferese , Adolescente , Adulto , Seguimentos , Rejeição de Enxerto/prevenção & controle , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Passive immunotherapy in human immunodeficiency virus (HIV) infection is based on transfusions of plasma that is rich in HIV antibodies. STUDY DESIGN AND METHODS: To verify whether the clearance of transfused antibodies will maintain an elevated titer of specific antibodies between biweekly transfusions of plasma, the titers of anti-HIV-1 in plasma and in transfusion recipients were measured. Samples from 12 recipients were analyzed by automated scanning of Western blot, before transfusion and at Days 2, 7, and 14 after transfusion. RESULTS: The p24 antibody became detectable or higher than the baseline after transfusion and remained detectable until the second transfusion. Anti-p24 titers were variable and dependent on the antibody titer of the transfused plasma and the baseline p24 antigen titer. CONCLUSION: Biweekly transfusion of plasma with a high anti-HIV titer maintains a high anti-p24 titer between transfusions in AIDS patients treated with passive immunotherapy.
Assuntos
Síndrome da Imunodeficiência Adquirida/terapia , Anticorpos Anti-HIV/sangue , Imunoterapia Adotiva , Síndrome da Imunodeficiência Adquirida/imunologia , Proteína do Núcleo p24 do HIV/sangue , Proteína do Núcleo p24 do HIV/imunologia , HumanosRESUMO
BACKGROUND AND OBJECTIVES: In human immunodeficiency virus (HIV) infections, passive immunotherapy can be carried out through infusions of virus-inactivated plasma from symptomless HIV-infected persons with abundant HIV antibodies. MATERIALS AND METHODS: We carried out a prospective, randomized, double-blind, controlled, passive immunotherapy study, which compared two groups. One received plasma rich in HIV antibodies, the other a standard seronegative plasma. RESULTS: Measurement of the plasma HIV RNA load showed in both groups a significant decrease in the mean viral copy number at the end of the first month, followed by an increase at the third month. Beyond the third months, a significant decrease in viral load was observed only in the treatment group. A significant difference in favor of the treatment group was observed for plasma viremia by HIV culture. For the cytokines involved in the viral replication and for the immune activation markers such as neopterin and beta 2-microglobulin, the biological analysis in plasma failed to show a significant difference in either group. Clinically, the treatment group benefited by delay in the appearance of the first AIDS-defining event and reduction in the cumulative incidence of such events. CONCLUSION: One possible interpretation is that passive immunotherapy affects plasma viral load, but there is no evidence that HIV-specific antibodies are exclusively responsible for the observed effects.
Assuntos
Síndrome da Imunodeficiência Adquirida/terapia , Transfusão de Sangue , Anticorpos Anti-HIV/sangue , Imunização Passiva/métodos , Biomarcadores/sangue , Estudos Transversais , Método Duplo-Cego , Humanos , Interleucina-1/sangue , Interleucina-6/sangue , Estudos Prospectivos , Fator de Necrose Tumoral alfa/análise , Carga Viral , Microglobulina beta-2/análiseRESUMO
Recent studies have shown that transfusions of HLA-compatible donor lymphocytes may induce complete remission in marrow-grafted patients with relapses of acute myeloblastic leukemia (AML). We investigated the in vitro generation of antileukemia T-cell clones obtained from the peripheral blood mononuclear cells of a partially HLA-compatible donor (HLA-A2 and B7 molecules in common with the leukemic blasts) after stimulation with a pool of naturally processed peptides extracted from leukemic blast cells collected at diagnosis from a patient with hyperleucocytosis AML. We recovered a significant quantity of peptides that bound to the HLA-A2 or HLA-B7 molecules that were able to induce cytolytic T-lymphocyte (CTL) lines and clones specific for the eluted AML peptides and restricted to the HLA-A2 or B7 molecules. Such CTL line did not recognize the patient's nonleukemic cells, and one clone was able to interact with the leukemic blasts from which the naturally processed peptides had been eluted. Such T-cell clones might provide a rationale for the development of adoptive immunotherapy and could be used to improve the efficiency of HLA-compatible T-lymphocyte transfusions and the graft-versus-leukemia response in patients with AML.
Assuntos
Apresentação de Antígeno , Antígenos de Neoplasias/imunologia , Leucemia Mieloide Aguda/imunologia , Linfócitos T Citotóxicos/imunologia , Antígeno HLA-A2/imunologia , Antígeno HLA-B7/imunologia , Humanos , Leucemia Mieloide Aguda/patologia , Ativação Linfocitária , Peptídeos/imunologia , Células Tumorais CultivadasRESUMO
A randomized double-blind controlled trial was conducted to determine the efficacy of passive immunotherapy in the treatment of symptomatic human immunodeficiency virus (HIV) infection. This trial included 86 symptomatic patients randomized to receive plasma rich in anti-HIV-1 antibody or standard seronegative plasma. Each patient in both groups received a 300-ml infusion every 14 days over a 1-year period, and every 28 days thereafter, in addition to zidovudine and other conventional prophylactic treatments. Plasma donors were selected among symptomless seropositive individuals with a CD4 lymphocyte count > or = 400 x 10(6) cells per liter, a negative p24 antigen assay, and a high concentration of anti-p24 antibody. The plasmas were heat-inactivated before infusion. During the study period (day 28-day 365) scheduled by the protocol, clinical benefit from passive immunotherapy was observed in delaying the appearance of the first AIDS-defining event (P < 0.009) and reducing the cumulative incidence of such events, which was estimated 3-fold higher in the control group compared to the treatment group. Seven deaths occurred in the treatment group vs. 11 in the control group (P = 0.27). A total of 47 patients died or exhibited new AIDS-defining events, 18 in the treatment group and 29 in the control group (P = 0.009). No clinical benefit was observed after the 1-year period with infusions performed every 4 weeks. These results indicate a favorable effect of passive immunotherapy on the evolution of advanced AIDS.
Assuntos
Síndrome da Imunodeficiência Adquirida/terapia , Transfusão de Sangue , Anticorpos Anti-HIV/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Adulto , Método Duplo-Cego , Feminino , Soronegatividade para HIV , Humanos , Imunoterapia Adotiva , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To evaluate the feasibility, safety, and efficacy of intensified-dose cyclophosphamide (ID-CYC), followed by granulocyte colony-stimulating factor (G-CSF) administration for collection of peripheral blood hematopoietic stem cells (HSC), for patients with severe, refractory rheumatoid arthritis (RA). METHODS: Four patients with severe refractory RA were enrolled in this open study. They received a single infusion of CYC (4 gm/m2) at day 0 followed by G-CSF (5 microg/kg/day) from day 6 until the last day of leukapheresis (performed at the time of hematopoietic recovery) to harvest peripheral blood HSC. Patients were monitored for disease activity, adverse effects, and hematopoietic reconstitution following this procedure. RESULTS: For all patients, administration of ID-CYC induced an early, dramatic improvement of disease activity. Long-term followup indicates that partial disease relapse was observed for all patients. No adverse effect was directly attributable to the treatment procedure. For most patients, HSC collection was sufficient to provide a graft enriched in CD34+ cells by positive selection as well as an unselected rescue graft. CONCLUSION: Patients with severe, refractory RA can benefit from ID-CYC. This procedure, followed by G-CSF administration, appears safe and technically suitable. In addition, it allows immediate improvement of RA activity that can occasionally persist beyond 6 months.