RESUMO
OBJECTIVE: To evaluate the outcome of children who received prolonged intravenous immunoglobulin (IVIg) replacement therapy early in life for X-linked agammaglobulinemia (XLA). STUDY DESIGN: We performed a retrospective study of the clinical features and outcome of patients with genetic and/or immunologic results consistent with XLA. Patients receiving IVIg replacement therapy within 3 months of the diagnosis and for at least 4 years between 1982 and 1997 were included. RESULTS: Thirty-one patients began receiving IVIg replacement therapy at a median age of 24 months and were followed up for a median time of 123 months. IVIg was given at doses >0.25 g/kg every 3 weeks, and mean individual residual IgG levels ranged from 500 to 1140 mg/dL (median, 700 mg/dL). During IVIg replacement, the incidence of bacterial infections requiring hospitalization fell from 0.40 to 0.06 per patient per year (P <. 001). However, viral or unidentified infections still developed, including enteroviral meningoencephalitis (n = 3) causing death in one patient, exudative enteropathy (n = 3), and aseptic arthritis (n = 1). At last follow-up, 30 patients were alive at a median age of 144 months (range, 58 to 253 months). Among 23 patients who were evaluated by respiratory function tests and computed tomography, 3 had an obstructive syndrome, 6 had bronchiectasis, and 20 had chronic sinusitis. CONCLUSION: Early IVIg replacement therapy achieving residual IgG levels >500 mg/dL is effective in preventing severe acute bacterial infections and pulmonary insufficiency. More intensive therapy may be required to fully prevent the onset of bronchiectasis, chronic sinusitis, and nonbacterial infections, particularly enteroviral infections, in all cases.
Assuntos
Agamaglobulinemia/genética , Agamaglobulinemia/terapia , Imunoglobulinas Intravenosas/uso terapêutico , Agamaglobulinemia/complicações , Agamaglobulinemia/imunologia , Criança , Pré-Escolar , Seguimentos , Ligação Genética , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Imunofenotipagem , Lactente , Infecções/etiologia , Estudos Retrospectivos , Cromossomo XRESUMO
A 2-year-old child had a metachromatic leukodystrophy-variant phenotype mainly involving the peripheral nervous system (PNS) that was caused by saposin-B deficiency. Bone marrow transplantation resulted in transient deterioration then continuous improvement of PNS functions. These findings were supported by nerve conduction velocity measurements, but the symptoms ultimately worsened. Magnetic resonance imaging showed persistent white matter lesions and progressive pontocerebellar atrophy.
Assuntos
Transplante de Medula Óssea , Glicoproteínas/deficiência , Leucodistrofia Metacromática/terapia , Encéfalo/patologia , Pré-Escolar , Humanos , Leucodistrofia Metacromática/patologia , Leucodistrofia Metacromática/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Condução Nervosa , Sistema Nervoso Periférico/fisiologia , Saposinas , Proteínas Ativadoras de EsfingolipídeosRESUMO
We report severe aplastic anemia of neonatal onset diagnosed in six girls between 1985 and 1995 in a single center. Initial blood cell counts (mean age 3.8 days old, 1 to 15 days) showed thrombocytopenia (six of six), anemia (four of six), and neutropenia (two of six). Neutrophil counts gradually decreased below 0.5 x 10(9)/L, and severe aplastic anemia occurred in three patients by 3 months of age and in all patients by 1 year of age. Lymphocyte number and functions were normal. In all children bone marrow biopsy showed hypocellularity for age and absence of fibrosis, blasts, lymphocytic infiltrates, and cytologic abnormalities. Blood and medullary cytogenetic studies were normal. A search for known constitutional, viral, or toxic causes was negative. Immunosuppressive therapy failed to restore hematopoiesis (three of six). Five children received a bone marrow transplantation at an average age of 9 months (range 2.7 to 29 months). One child is alive and well after a human leukocyte antigen-identical bone marrow transplantation, whereas the other four died. Both congenital onset and the high rate of familial involvement suggest that this condition may be inherited.
Assuntos
Anemia Aplástica/epidemiologia , Anemia Aplástica/diagnóstico , Anemia Aplástica/genética , Anemia Aplástica/terapia , Biópsia , Contagem de Células Sanguíneas , Transfusão de Sangue , Medula Óssea/patologia , Transplante de Medula Óssea , Feminino , Hematopoese/fisiologia , Humanos , Lactente , Recém-Nascido , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Human immunodeficiency virus type 2 infection is rare in children. This virus can be acquired through transfusion and also by the maternofetal route, especially when the mother becomes infected during pregnancy. Diagnosis based on specific serologic tests is simple after the age of 18 months. In the perinatal period, however, viral isolation by culture or polymerase chain reaction DNA amplification or both appears to be less sensitive than in the case of human immunodeficiency virus type 1. Disease progression is far slower than with human immunodeficiency virus type 1, but severe immunodeficiency can occur.
Assuntos
Soropositividade para HIV/sangue , HIV-2/isolamento & purificação , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Adolescente , Criança , Pré-Escolar , Infecções por Deltaretrovirus/sangue , Infecções por Deltaretrovirus/transmissão , Ensaio de Imunoadsorção Enzimática , Soropositividade para HIV/transmissão , Humanos , Lactente , Recém-Nascido , Reação em Cadeia da PolimeraseRESUMO
We studied the propagation and the impact of zidovudine prevention on the human immunodeficiency virus-1 transmission rate from infected mothers to their infants in the French nationwide prospective cohort. Infection was diagnosed in the children on the basis of at least two positive human immunodeficiency virus-1 polymerase chain reaction tests, culture, or both. The transmission rate among treated women was compared with that among untreated women during the same period and with that among women enrolled in the cohort since 1986. The impact of zidovudine was analyzed according to the women's clinical and biologic characteristics, the mode of delivery, and use of zidovudine therapy before the pregnancy. Nearly 90% of women were treated as soon as the second half of 1994. In 1994 and 1995, 80% of mother-child pairs received at least one of the three phases of preventive treatment. Among the 663 mothers enrolled during these 2 years, only six refused the treatment. Zidovudine treatment was associated with a reduction in the transmission rate of nearly two-thirds, from 14% +/- 6% to 5% +/- 2% (p < 0.01). The degree of reduction was not influenced by the maternal CD4+ cell count or p24 antigenemia at delivery. Zidovudine treatment of the mother before the pregnancy considerably reduced the impact of preventive therapy; the transmission rate was significantly higher among pretreated mothers (20% versus 5%, p < 0.01) even after adjusting for maternal CD4+ cell count. Zidovudine prevention is now widely used in France and has had a major impact on the epidemiology of mother-child human immunodeficiency virus transmission. This justifies a policy of offering human immunodeficiency virus screening to all women before or shortly after the diagnosis of pregnancy.
Assuntos
Síndrome da Imunodeficiência Adquirida/prevenção & controle , Fármacos Anti-HIV/uso terapêutico , Soropositividade para HIV/tratamento farmacológico , Soropositividade para HIV/transmissão , HIV-1 , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/tratamento farmacológico , Zidovudina/uso terapêutico , Síndrome da Imunodeficiência Adquirida/epidemiologia , Estudos de Coortes , Intervalos de Confiança , Feminino , França/epidemiologia , Soropositividade para HIV/imunologia , Humanos , Recém-Nascido , Análise Multivariada , Razão de Chances , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Estudos Prospectivos , Medição de RiscoRESUMO
Congenital erythropoietic porphyria (Gunther disease) is a rare metabolic disorder caused by uroporphyrinogen III synthetase deficiency. We report the case of a 2-year-old girl with a severe form of this disease who received HLA-identical bone marrow transplantation from her heterozygous sister. Two transplantations were necessary to obtain full hematopoietic chimerism. Correction of the enzyme deficiency was confirmed by measuring erythrocyte uroporphyrinogen III synthetase activity. The patient's clinical condition improved dramatically, and she is well 1 year after the second transplantation, with no further treatment. Although long-term efficacy remains to be confirmed, we conclude that allogeneic bone marrow transplantation can cure patients with congenital erythropoietic porphyria.
Assuntos
Transplante de Medula Óssea , Porfiria Eritropoética/terapia , Pré-Escolar , Feminino , Humanos , Porfiria Eritropoética/diagnóstico , ReoperaçãoRESUMO
We retrospectively analyzed the outcome of bone marrow transplantation (BMT) performed in 26 patients with Wiskott-Aldrich syndrome (WAS) in one center. Twenty-eight transplantation procedures were performed. Ten unselected patients received unmanipulated marrow from a donor with genetically identical human leukocyte antigen (HLA). Eight patients were cured and survive 1.5 to 16.5 years after BMT. One patient successfully received a T-cell-depleted marrow from a matched unrelated donor. Sixteen patients were selected to receive a related HLA partially incompatible BMT because of the occurrence of life-threatening complications from the WAS (i.e., refractory thrombocytopenia, autoimmunity including vasculitis and sepsis). All but one received T-cell-depleted marrow after a conditioning regimen of busulfan and cyclophosphamide. One patient had two BMTs. Engraftment occurred in 12 of 17 attempts. The addition of monoclonal antibodies to lymphocyte function-associated antigen-1 and CD2 molecules appeared to improve engraftment. Six patients were long-term survivors, whereas others died of viral infections (n = 7), among which Epstein-Barr virus-induced B-lymphocyte proliferative disorder was predominant. Delay in development of full T- and B-cell functions accounted for severe infectious complications. These results confirm the excellent outcome of HLA genetically identical BMT in WAS, whereas BMT from HLA partially incompatible donors should be strictly restricted to patients with severe complications of WAS.
Assuntos
Transplante de Medula Óssea , Síndrome de Wiskott-Aldrich/terapia , Adolescente , Anticorpos Monoclonais/uso terapêutico , Doenças Autoimunes/complicações , Linfócitos B/imunologia , Bussulfano/uso terapêutico , Antígenos CD2/uso terapêutico , Criança , Pré-Escolar , Ciclofosfamida/uso terapêutico , Sobrevivência de Enxerto , Antígenos HLA/genética , Infecções por Herpesviridae , Herpesvirus Humano 4 , Humanos , Imunossupressores/uso terapêutico , Lactente , Depleção Linfocítica , Antígeno-1 Associado à Função Linfocitária/uso terapêutico , Estudos Retrospectivos , Sepse/complicações , Taxa de Sobrevida , Linfócitos T/imunologia , Trombocitopenia/complicações , Resultado do Tratamento , Vasculite Leucocitoclástica Cutânea/complicaçõesRESUMO
We report the outcome of allogeneic bone marrow transplantation (BMT) in nine consecutive patients with Omenn syndrome treated between 1980 and 1989. Five patients received unmanipulated marrow from a related matched donor, and four received T cell-depleted marrow from a haploidentical donor. The patients were conditioned with cyclophosphamide (200 mg/kg) and, except in one case, busulfan (16 mg/kg). Antithymocyte globulin and etoposide were given to three patients each; three recipients of T cell-depleted haploidentical marrow also received intravenous injections of an anti-leukocyte function-associated antigen type 1 antibody as graft rejection prophylaxis. All the patients were fed parenterally for 1 to 5 months before BMT to improve nutritional status and received topical corticosteroids (n = 8), systemic steroids (n = 2), etoposide (n = 1), or cyclosporine (n = 1) to control T-cell activation. Engraftment occurred in four of five recipients of human leukocyte antigen (HLA)-identical marrow and three of four recipients of HLA-haploidentical marrow. One patient died with cytomegalovirus infection. The other six patients are alive 4 to 11 years after BMT, with full chimerism in all but one case. Chronic graft-versus-host disease persists in one patient; the other five survivors have fully restored immune function and have no manifestations of Omenn syndrome, including failure to thrive. We conclude that both HLA-identical and haploidentical BMT can cure Omenn syndrome, provided that parenteral nutrition and immunosuppressive therapy are given before transplantation.
Assuntos
Transplante de Medula Óssea , Imunodeficiência Combinada Severa/terapia , Bussulfano/administração & dosagem , Bussulfano/uso terapêutico , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Feminino , Rejeição de Enxerto/prevenção & controle , Doença Enxerto-Hospedeiro/tratamento farmacológico , Antígenos HLA/sangue , Haplótipos , Humanos , Imunoglobulinas/sangue , Masculino , Estado Nutricional , Estudos Retrospectivos , SíndromeRESUMO
Thirty-three children vertically infected with human immunodeficiency virus type 1 (HIV-1), who were born before 1985, were followed in a single center, and had reached the age of 6 years, were studied and tested for school achievement. Of these 33 children, 24 were also tested for cognitive abilities, fine motor and language skills, and emotional adaptation. Of the 33 patients, 22 (67%) had normal school achievement at a mean age of 9.5 +/- 1.6 years. The mean IQ was 95 +/- 11, but 54% of the patients (13/24) had abnormal results on visual-spatial and time orientation tests, 44% had speech and/or language delay or articulation disorders, and 29% of the children and 42% of the parents had psychoaffective disturbances of intermediate or high severity. Normal school performance was positively correlated with results of the different cognitive tests and to a lesser extent with the absence of psychoaffective symptoms, but was independent of the mode of maternal infection or the parents' educational level. Children with normal school achievement had a higher percentage of circulating CD4+ lymphocytes during the course of infection. We conclude that children whose HIV-1 infection is maternally acquired have better cognitive abilities and school achievement than was initially thought, and that the percentage of circulating CD4+ lymphocytes during the first years of life appears to be predictive of future school adaptation or cognitive abilities.
Assuntos
Síndrome da Imunodeficiência Adquirida/psicologia , Cognição , HIV-1 , Transmissão Vertical de Doenças Infecciosas , Síndrome da Imunodeficiência Adquirida/imunologia , Síndrome da Imunodeficiência Adquirida/transmissão , Contagem de Linfócito CD4 , Criança , Transtornos do Comportamento Infantil/etiologia , Linguagem Infantil , Avaliação Educacional , Feminino , Humanos , Inteligência , Estudos Longitudinais , Mães , Destreza Motora , Testes PsicológicosRESUMO
We conducted a prospective, open study of oral itraconazole therapy (5 and then 10 mg/kg per day) to assess tolerance and potential efficacy in preventing fungal infections in patients with chronic granulomatous disease. Thirty-two patients were enrolled in one center between 1985 and 1991. Tolerance was excellent in all cases. Poor compliance was suspected in three cases. Two patients were excluded from efficacy analysis because itraconazole was used as part of therapy for pulmonary aspergillosis. Of 30 patients, 3 developed a fungal (Aspergillus) lung infection, an incidence 3.4/100 patient-years versus 11.5 in a historical control group that did not receive any prophylaxis (p = 0.13) and 9.55 in a historical group of patients who received daily ketoconazole prophylaxis (p = 0.19). The percentage of patients infected with Aspergillus was significantly different: 10% in the itraconazole group versus 34.4% in the untreated group (p = 0.013). These results require further evaluation through a comparative randomized trial to assess the possible benefit of itraconazole prophylaxis in patients with chronic granulomatous disease.
Assuntos
Aspergilose/prevenção & controle , Doença Granulomatosa Crônica/complicações , Itraconazol/uso terapêutico , Cetoconazol/uso terapêutico , Pneumopatias Fúngicas/prevenção & controle , Administração Oral , Aspergilose/sangue , Aspergilose/epidemiologia , Aspergilose/etiologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Incidência , Lactente , Itraconazol/farmacocinética , Pneumopatias Fúngicas/sangue , Pneumopatias Fúngicas/epidemiologia , Pneumopatias Fúngicas/etiologia , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
We carried out a retrospective analysis of 117 patients with severe combined immunodeficiency who were examined in a single center between Jan. 1, 1970, and Jan. 1, 1992, for the purpose of evaluating disease onset, progression, and outcome. The frequency of case referral increased from 8 from 1970 to 1975 to 56 from 1986 to 1991. The most frequent phenotype was T-/B+ (absence of T lymphocytes and presence of B lymphocytes) (n = 51); there were 36 cases of alymphocytosis, 16 of adenosine deaminase deficiency, 13 of Omenn syndrome, and 1 of reticular dysgenesis. Protracted diarrhea and lung infections were the main infectious complications; infection with bacillus Calmette-Guérin occurred in 10 of 28 vaccinated patients, but none of the six recipients of oral polio vaccine subsequently had poliomyelitis. The presence of maternal T cells was suspected or proved in half the patients with alymphocytosis or T-B+ severe combined immunodeficiency but did not occur in the other forms of the disease. Of the 117 patients, 22 died before transplantation could be performed. Adenosine deaminase deficiency and Omenn syndrome were more frequently associated with death before hematopoietic stem cell transplantation was possible. Fetal liver transplantation was successful in 1 of 10 cases. The survival rate among the 30 recipients of bone marrow with identical human leukocyte antigens (HLA) was 80%, with a median follow-up of 129 months; 23 of 25 patients recovered full immune function. The survival rate among the 50 recipients of HLA-haploidentical T cell-depleted bone marrow was 56%, with a mean follow-up of 35 months. Of the latter patients, 10 (35%) still require immunoglobulin substitution. There has been a trend toward improvement in the survival rate of haploidentical bone marrow recipients, presumably because of more effective infection-control measures and better transplantation strategy.
Assuntos
Imunodeficiência Combinada Severa/epidemiologia , Transplante de Medula Óssea , Feminino , Transplante de Tecido Fetal , Humanos , Imunofenotipagem , Incidência , Lactente , Recém-Nascido , Transplante de Fígado , Masculino , Prevalência , Estudos Retrospectivos , Imunodeficiência Combinada Severa/imunologia , Imunodeficiência Combinada Severa/terapia , Análise de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
2'3'-Dideoxyinosine (didanosine) is a nucleoside analog active in vitro against human immunodeficiency virus. Few data are available regarding its use for the treatment of children. In a single-center, randomized, open-label trial, we compared two dosages of didanosine (120 vs 270 mg/m2 per day) for at least 6 months in 34 children infected with human immunodeficiency virus who had become resistant to or were intolerant of zidovudine. Serum levels of didanosine 1 hour after administration were significantly different in the two groups and remained stable with time. There was a significant reduction in human immunodeficiency virus-p24 antigenemia and quantitative cellular viremia with time but no difference between the two groups. The intensity of the biologic response, however, was significantly higher in the patients who had more than 50 CD4+ cells 10(6)/L at inclusion. No pancreatic or neurologic toxic effects were observed. In five children, liver function abnormalities developed that are unusual in this setting, and the death of one child from unexplained hepatocellular failure suggests that didanosine may be hepatotoxic. Three of these five children had preexisting liver disease. Although no definite conclusion can be made as to the optimal dose, there were no major differences between the two administration schedules in terms of biologic effects and tolerability.
Assuntos
Didanosina/administração & dosagem , Infecções por HIV/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Feminino , HIV/isolamento & purificação , Proteína do Núcleo p24 do HIV/análise , Infecções por HIV/microbiologia , Humanos , Lactente , Masculino , ViremiaRESUMO
Graft rejection is the major cause of failure of HLA mismatched bone marrow transplantation because of residual host immunity. we have proposed to use a monoclonal murine antibody specific for the LFA-1 molecule (25-3) to prevent graft failure in HLA mismatched bone marrow transplantation (BMT). The rationale for this approach is three fold: LFA-1 deficient patients (3/3) do not reject HLA mismatched BMT; anti LFA-1 blocka in vitro the induction of T cell responses and T/ non T cytotoxic functions; LFA-1 is not expressed by other cells than leucocytes. We have accordingly treated twenty two patients with inherited diseases and 8 with leikemia. The bone marrow was T cells depled by E rosetting of Campath antibody. The antibody was given at days -3, -1, +1, +3, +5 at dose of .1 mg/kg/d for the first 9 and then .2mg/kg/d from day -3 to +6. Engraftment occured in 23/30 patients as shown by at least HLA typing. Hematological recovery was rapid, GVH was limited. Side effects of antibody infusion included fever and possibly an increased incidence of early bacteral infection (sepsis, 1 death). Immunological reconstitution occured slowly leading in six cases to EBV-induced B cell poliferation (1 death and in two others to transient auto immune hemolytic anemia. There has been only one secondary graft rejection. Sisteen patients are alive 3 to 26 months post transplant with functional grafts. Although the number of patients treated is still low the absence of late rejection so far, gives hope for long term maintenance of the graft using anti LFA-1. Since the antibody is an IgG 1 unable to bind human complement, and since it is known to inhibit phagocytosis, there is a good suggestion that 25-3 act through functional blocking of host T and non T luymphocytes at both induction and effector levels.
Assuntos
Humanos , Células da Medula Óssea/citologia , Anticorpos Monoclonais , Antígeno-1 Associado à Função Linfocitária , Afinidade de AnticorposRESUMO
We performed a longitudinal study (mean follow-up 19.5 months, range 3 to 42 months) in 18 consecutive children with clinical symptoms of LAV/HTLV III infection. Twelve patients were born to mothers infected with LAV/HTLV III, and six were infected by blood products administered during the first weeks of life. Immunologic studies included lymphocyte markers, in vitro responses to mitogens and antigens with corresponding skin tests, and antibody response with isoagglutinins, post-vaccination antibodies, and Candida. A serologic profile of antibody to GP110, P18, and P25 LAV/HTLV III antigens by radioimmunoprecipitation assay was also performed. The antigen-induced proliferative responses were normal in 10 patients who had a stable course, but were profoundly impaired in eight others who died or had poor condition with opportunistic infections. These in vitro measurements were well correlated with antigen skin tests. An abnormal antibody response to antigens, a low level of isoagglutinins, and a peculiar profile of LAV/HTLV III antibodies were also frequently observed in these eight patients. These measurements appear to be of prognostic value because they were noticed soon after onset of clinical symptoms.
Assuntos
Síndrome da Imunodeficiência Adquirida/imunologia , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/mortalidade , Síndrome da Imunodeficiência Adquirida/transmissão , Anticorpos Antivirais/análise , Formação de Anticorpos , Pré-Escolar , Homólogo 5 da Proteína Cromobox , Insuficiência de Crescimento/etiologia , Humanos , Imunidade Celular , Lactente , Estudos Longitudinais , Ativação Linfocitária , Infecções Oportunistas/etiologia , Prognóstico , VacinaçãoAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Doenças Linfáticas/terapia , Pré-Escolar , Teste de Histocompatibilidade , Humanos , Doenças Linfáticas/genética , Doenças Linfáticas/imunologia , Masculino , Fagocitose , Transplante HomólogoRESUMO
On the basis of four cases of patients with persistent lymphadenopathy and at risk for acquired immune deficiency syndrome (AIDS), (3 Haitians, one haemophiliac), histopathologic features of lymph node biopsy in AIDS are recalled. Two main types of alterations of lymph node architecture--follicular hyperplasia or lymphoid depletion--can be associated with interfollicular lesions: vascular proliferation, numerous plasma cells, epithelioid reaction that may reflect an infectious process. Alterations of T-cell subsets distribution were also analyzed using immunocytochemical labelling of frozen sections from lymph nodes. In all four cases, T4 (helper)--lymphocytes were markedly depleted, whereas they normally represent the majority of lymph node T cells. They were replaced by prominent T8 (cytotoxic, suppressor)-cells, particularly inside the follicle. T8 lymphocytes are usually rare in this latter area. The fine analysis of these abnormalities is useful in prodromal or mild forms of AIDS.