RESUMO
INTRODUCTION: The life expectancy of ß-thalassemia patients has increased over the last 20 years. In this study, we evaluated the current health status and quality of life of these patients managed in a reference center in Marseille. METHODS: This is a single-center, descriptive study conducted between June and August 2019 in patients over 18 years of age with ß-thalassemia major or intermedia. Clinical and paraclinical data were collected retrospectively and the SF-36 health survey questionnaire was proposed to each patient. RESULTS: 43 of 64 selected patients were included and divided into 2 groups: 35 patients with transfusion-dependent ß-thalassemia and 8 patients with non-transfusion-dependent ß-thalassemia. Liver iron overload is the most frequent complication, present in 80% of transfusion-dependent and 62.5% of non-transfusion-dependent patients. Cardiac iron overload is present only in the transfusion dependent ß-thalassemia group (20%). Hypogonadotropic hypogonadism remains the most common endocrine disorder (41.9%) followed by osteoporosis (37.2%). Among the 31 patients who completed the SF-36 questionnaire, physical and mental quality of life scores were lowered in transfusion dependent (respectively 42.7 and 46.8) as in non-transfusion-dependent patients (respectively 43.8 and 28.9). CONCLUSION: Despite an improvement in medical care, our patients with ß-thalassemia show an alteration in their quality of life that will need to be characterized in the entire French cohort.
Assuntos
Nível de Saúde , Qualidade de Vida , Talassemia beta , Humanos , Talassemia beta/terapia , Talassemia beta/epidemiologia , Talassemia beta/complicações , Talassemia beta/psicologia , França/epidemiologia , Masculino , Feminino , Adulto , Estudos Retrospectivos , Adulto Jovem , Pessoa de Meia-Idade , Transfusão de Sangue/estatística & dados numéricos , Sobrecarga de Ferro/epidemiologia , Sobrecarga de Ferro/etiologia , Inquéritos e Questionários , AdolescenteRESUMO
Little information is available on erythrocytapheresis in children with sickle cell disease, and no comparison has ever been made with manual exchanges in a long-term blood exchange program. We matched a historical cohort of five patients who received 60 erythrocytapheresis procedures with five who received 124 manual exchanges. Long-term erythrocytapheresis was feasible and well-tolerated even in children of low weight. In a long-term approach, automated exchanges were more efficient in maintaining a low HbS level, and exchanges could be spaced out. This approach appears especially useful in the cases where the HbS level must be maintained below 30%.
Assuntos
Anemia Falciforme/terapia , Transfusão de Eritrócitos , Adolescente , Anemia Falciforme/sangue , Criança , Pré-Escolar , Feminino , Hemoglobina Falciforme/metabolismo , Humanos , Masculino , Estudos Retrospectivos , Fatores de TempoRESUMO
Hereditary spherocytosis (HS) is the commonest inherited disorder of the erythrocyte membrane in Northern Europe and North America. It is marked by a regenerative anemia which varies widely from asymptomatic patients to severe hemolysis. In 75% of HS patients, inheritance is autosomal dominant. The diagnosis of HS is easily made when there are a family history, hemolytic anemia, reticulocytosis, spherocytes and increased hyperdense cells. Specialized testing to clarify the nature of membrane disorder is required when the film appearance is atypical without a positive family history, in the absence of a family history, in the newborn and before the splenectomy, to rule out the stomatocytosis which is contraindicated. The indication for splenectomy is dependent on the degree of anemia and its clinical manifestation.
Assuntos
Esferocitose Hereditária/diagnóstico , Esferocitose Hereditária/terapia , Criança , Colecistectomia , Membrana Eritrocítica/fisiologia , Transfusão de Eritrócitos , Eritropoetina , Humanos , Proteínas Recombinantes , Esferocitose Hereditária/genética , EsplenectomiaRESUMO
We compared late side effects and quality of life (QoL) in 430 survivors of childhood acute leukaemia based on whether they had undergone haematopoietic cell transplantation (n=142) or not (n=288). Mean age was 18.2 years and mean follow-up duration was 11.9 years. Multivariate logistic regression analyses were performed to compare the risk of each type of late effect in the two groups. Based on age, VSP-A or SF36 questionnaires were used to assess QoL. For each QoL dimension, multiple linear regression was done to construct models of association with the treatment group. Transplanted patients experienced more side effects, including height growth failure, gonadal dysfunction, hypothyroidism and cataract. Children and adolescents in the two treatment groups reported similar QoL levels for almost all dimensions except a better perception of school work by young transplanted children and more difficulties in relating to the medical staff for transplanted adolescents. In adults, two differences in physical domain of QoL were detected but the calculated effect sizes were less than 0.2 in each case, suggesting an uncertain clinical significance. In spite of a higher risk of physical adverse events in the transplanted group, very few clinically significant differences in QoL are detectable.
Assuntos
Nível de Saúde , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia/complicações , Leucemia/terapia , Sobreviventes , Adolescente , Catarata/etiologia , Criança , Seguimentos , Transtornos Gonadais/etiologia , Transtornos do Crescimento/etiologia , Humanos , Hipotireoidismo/etiologia , Modelos Lineares , Inquéritos e QuestionáriosRESUMO
Cord blood (CB) units are increasingly used for allogeneic transplantation. Cell dose, a major factor for CB selection, is evaluated before freezing by each CB bank, using various techniques. This may introduce variability and affect the prediction of cell recovery after thawing, or haematopoietic reconstitution. Forty-two children were transplanted at the same institution with unrelated CB units. All units were thawed and evaluated at the same cell therapy facility, using standard procedures. We investigated: (i) factors that affect cell loss after thawing, and (ii) the importance of CD34(+) cell doses. Prefreeze and post-thaw CD34(+) cell doses were statistically correlated, thus suggesting that variability in numeration techniques used by different CB banks does not compromise the biological and clinical value of these figures. CD34(+) cell recovery appeared to be correlated with the absolute number of CD34(+) cells per frozen bag. Infused CD34(+) is the cell dose that better correlates with platelet reconstitution delay; in addition, when using a quartile comparison, haematopoietic recovery appeared to be related with prefreeze and post-thaw CD34(+) cell doses. We conclude that enumeration of CD34(+) cells in CB units is of biological significance, and may help select CB units and identify patients at risk of delayed recovery.
Assuntos
Antígenos CD34/sangue , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Neoplasias/terapia , Antígenos CD/sangue , Técnicas de Cultura de Células/normas , Criança , Transplante de Células-Tronco de Sangue do Cordão Umbilical/normas , Sangue Fetal , Transplante de Células-Tronco Hematopoéticas/normas , Humanos , Imunossupressores/uso terapêutico , Cinética , Contagem de Leucócitos , Contagem de Plaquetas , Reprodutibilidade dos Testes , Estudos Retrospectivos , Condicionamento Pré-Transplante , Transplante Homólogo , Irradiação Corporal TotalRESUMO
Measurement of serum ferritin (SF) is currently the laboratory test recommended for diagnosing iron deficiency. In the absence of an associated disease, a low SF value is an early and highly specific indicator of iron deficiency. The WHO criteria proposed to define depleted storage iron are 12µg/L for children under 5 years and 15µg/L for those over 5 years. A higher threshold of 30µg/L is used in the presence of infection or inflammation. Iron deficiency anemia, with typical low mean corpuscular volume and mean corpuscular hemoglobin, is only present at the end stage of iron deficiency. Other diagnostic tests for iron deficiency including iron parameters (low serum iron, increased total iron-binding capacity, low transferrin saturation) and erythrocyte traits (low mean corpuscular volume, increased zinc protoporphyrin) provide little additional diagnostic value over SF. In children, serum soluble transferrin receptor (sTfR) has been reported to be a sensitive indicator of iron deficiency and is relatively unaffected by inflammation. On the other hand, sTfR is directly related to extent of erythroid activity and not commonly used in clinical practice. In population surveys, approaches based on combinations of markers have been explored to improve the specificity and sensitivity of diagnostic. In addition to Hb value determination, a combination of parameters (among transferrin saturation, zinc protoporphyrin, mean corpuscular volume or serum ferritin) was generally used to assess iron deficiency. More recently sTfR/ ferritin index were evaluated, sTfR in conjunction with SF allowing to better distinguishing iron deficiency from inflammatory anemia. Also, hepcidin measurements appeared an interesting marker for diagnosing iron deficiency and identifying individuals in need of iron supplementation in populations where inflammatory or infectious diseases are frequently encountered. Reticulocyte Hb content (CHr) determination is an early parameter of iron deficiency erythropoiesis. CHr can be measured with several automated hematology analyzers and so, used for individual's iron status assessment. In addition to Hb concentration determination, individual's iron status is commonly assessed in the pediatric clinical practice by the SF measurement accompanied by the determination of C-reactive protein for detection of a simultaneous acute infection and/or inflammation.
Assuntos
Anemia Ferropriva/diagnóstico , Deficiências de Ferro , Biomarcadores/sangue , Criança , Ferritinas/sangue , Hemoglobinas/metabolismo , Hepcidinas/sangue , Humanos , Inflamação/diagnóstico , Proteínas de Membrana/genética , Protoporfirinas/sangue , Receptores da Transferrina/sangue , Reticulócitos/metabolismo , Serina Endopeptidases/genética , Talassemia beta/sangue , Talassemia beta/diagnósticoRESUMO
From 1989 to 1998, 341 children were included in the French multicentric LAME (Leucémie Aiguë Myéloblastique Enfant) trials. A total of 309 children were registered in the LAME 89/91 protocol. This intensive regimen included an induction phase (mitoxantrone plus cytarabine), two consolidation courses, one containing timed-sequential high-dose cytarabine, asparaginase and amsacrine; 276 (90%) achieved a CR. The 5-year overall survival (OS) and event-free survival (EFS) were 60+/-4 and 48+/-4%, respectively. From 1997, timed-sequencing of the LAME SP induction chemotherapy led to an unacceptable frequency of consolidation delay; future improvements are unlikely to come from further increases in intensity. The role of allogenic bone-marrow transplantation from an HLA-identical sibling in CR1 was examined. The disease-free survival (DFS) was 52+/-4% for non-allografted patients and 57+/-7% for allografted patients (P=NS); a better OS for allografted patients was shown and could be related either to allo-BMT early in CR1 or to a second allo-BMT in CR2. For the complete responders after consolidation therapy, the 5-year OS was significantly better in patients randomized for no maintenance therapy (MT-) than in patients randomized for MT (77.6+/-8 vs 59+/-8%; P=0.05), while the 5-year DFS was not significantly different. Exposure to low-dose MT might contribute to clinical drug resistance and treatment failure in relapsing patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos Antineoplásicos/normas , Leucemia Mieloide Aguda/terapia , Adolescente , Transplante de Medula Óssea , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Seguimentos , França , Humanos , Lactente , Recém-Nascido , Leucemia Mieloide Aguda/mortalidade , Indução de Remissão , Medição de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: We retrospectively analyzed the outcome of children with acute myeloid leukemia (AML) in first complete remission (CR) who received HLA-identical bone marrow transplantation (BMT) in 13 French transplant centers. PATIENTS AND METHODS: Seventy-four children were treated from June 1979 through December 1990. The conditioning regimen included total-body irradiation (TBI) in 54 cases and busulfan in 20. Prophylaxis of graft-versus-host disease (GVHD) consisted of cyclosporine (CycloA) plus methotrexate (MTX) for 38 patients, MTX for 17, CycloA for 18, and T depletion without other prophylaxis for one. The mean value of the interval from diagnosis to transplantation was 167 days. RESULTS: Sixteen patients died of transplant-related complications, 12 relapsed, and 46 are alive in continuous remission with a median follow-up of 46 months. We examined results obtained over three successive periods: 1979 to 1982 (n = 14 children), 1983 to 1986 (n = 29), and 1987 to 1990 (n = 31). Probabilities of event-free survival (EFS) were 43%, 48%, and 82% for the three successive periods, respectively (P < .02). This improvement in EFS was linked to a decreased risk of transplant-related mortality: 36%, 36%, and 3%, respectively (P < .01). Other factors associated with a better EFS in the univariate analysis were a short time interval from diagnosis to transplant (< 120 days), the absence of significant (grade > or = 2) acute GVHD, and the absence of chronic GVHD. In the multivariate analysis, two factors had a favorable impact on long-term survival: the year of transplantation (years 1987 to 1990 v others) and the absence of acute GVHD. CONCLUSION: The outcome for children receiving allogeneic BMT in first CR of AML has improved in France during recent years.
Assuntos
Transplante de Medula Óssea , Leucemia Mieloide/cirurgia , Doença Aguda , Adolescente , Análise de Variância , Transplante de Medula Óssea/efeitos adversos , Criança , Pré-Escolar , Ciclosporina/uso terapêutico , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Lactente , Masculino , Metotrexato/uso terapêutico , Análise de Regressão , Estudos Retrospectivos , Transplante Homólogo , Resultado do TratamentoRESUMO
PURPOSE: To analyze the French experience of chemotherapeutic preparation before human leukocyte antigen (HLA)-identical bone marrow transplantation (BMT) in children with acute myeloblastic leukemia (AML) in first complete remission (CR). PATIENTS AND METHODS: The data base used for this study was a French BMT registry for childhood AML. Twenty-three children were conditioned with busulfan and 120 mg/kg cyclophosphamide (Bu-Cy 120 group). Nineteen received busulfan and 200 mg/kg cyclophosphamide (Bu-Cy200 group). During the same time period, 32 patients were prepared with total-body irradiation (TBI group) most often in combination with 120 mg/kg of cyclophosphamide. RESULTS: The probability of relapse was 54%, 13%, and 10% for the Bu-Cy120, Bu-Cy200, and TBI groups, respectively (P < .05 in the univariate analysis, log-rank test, 2 df). In the multivariate analysis, a conditioning regimen with Bu-Cy120 was significantly associated with a higher risk of relapse (P = .02; relative risk, 3.62). The probability of transplant-related mortality (TRM) was 0% for Bu-Cy120, 5% for Bu-Cy200, and 10% for TBI. Kaplan-Meier estimations of event-free survival (EFS) were 46% +/- 24%, 82% +/- 18%, and 80% +/- 14%, respectively, for the three groups, with median follow-up durations of 28 months (range, 3 to 78), 31 months (4 to 68), and 48 months (2 to 73). In the multivariate analysis, two factors adversely affected EFS: a conditioning regimen with Bu-Cy120 (P = .07) and a long interval from diagnosis to BMT (> or = 120 days, P = .08). CONCLUSION: Bu-Cy120 is a well-tolerated preparation, but results in a high risk of relapse for children with AML in first CR. This high risk of relapse is not observed when the dose of cyclophosphamide is increased to 200 mg/kg.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Leucemia Mieloide Aguda/terapia , Irradiação Corporal Total , Bussulfano/administração & dosagem , Criança , Pré-Escolar , Terapia Combinada , Ciclofosfamida/administração & dosagem , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Recidiva , Indução de Remissão , Taxa de SobrevidaRESUMO
PURPOSE: The French Society of Pediatric Oncology MDH82 study demonstrated the effectiveness of 20 Gy irradiation of involved fields after doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or mechlorethamine, vincristine, procarbazine, and prednisone/ABVD chemotherapy in children with localized Hodgkin's disease (HD). The response to primary chemotherapy was the only predictor of survival. To reduce long-term treatment complications without compromising efficacy, the MDH90 study was based on a new chemotherapy regimen devoid of both alkylating agents and anthracycline, followed by 20 Gy of radiotherapy (RT) for good responders. PATIENTS AND METHODS: From January 1990 to July 1996, 202 children were enrolled from 30 institutions. Good responders to four cycles of vinblastine, bleomycin, etoposide (VP16), and prednisone (VBVP) were given 20 Gy of RT and no further therapy. Poor responders were given vincristine, procarbazine, prednisone, and doxorubicin. After a second evaluation, good responders were given 20 Gy of RT, and poor responders were given 40 Gy of RT. RESULTS: One hundred seventy-one patients (85%) were good responders to VBVP, 27 (15%) were poor responders, and four did not respond. With a median follow-up of 74 months (range, 25 to 117 months), the 5-year overall survival rate (mean +/- SD) is 97.5% +/- 2.1%, and the event-free survival rate (mean +/- SD) is 91.1% +/- 1.8%. Significant predictors of worse event-free survival in multivariate analysis were hemoglobin < 10.5 g/L, "b" biologic class, and nodular sclerosis. CONCLUSION: These results suggest that most children with clinical stage I and II HD can be treated with chemotherapy devoid of alkylating agents and anthracycline, followed by low-dose RT.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Adolescente , Bleomicina/administração & dosagem , Criança , Pré-Escolar , Terapia Combinada , Dacarbazina/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Doença de Hodgkin/patologia , Humanos , Masculino , Prednisona/administração & dosagem , Dosagem Radioterapêutica , Resultado do Tratamento , Vimblastina/administração & dosagemRESUMO
PURPOSE: To clarify treatment strategy for lymphocyte-predominant Hodgkin's lymphoma (LPHL), the French Society of Pediatric Oncology initiated a prospective, nonrandomized study in 1988. Patients received either standard treatment for Hodgkin's lymphoma or were not treated beyond initial adenectomy. PATIENTS AND METHODS: From 1988 to 1998, 27 patients were available for study. Twenty-four patients were male, and median age was 10 years (range, 4 to 16 years). Twenty-two, two, and three patients had stage I, II, and III disease, respectively. Thirteen patients (stage I, n = 11; stage III, n = 2) received no further treatment after initial surgical adenectomy (SA). Fourteen patients received combined treatment (CT; n = 10), involved-field radiotherapy alone (n = 1), or chemotherapy alone (n = 3). The two groups were comparable for clinical status, treatment, and follow-up. RESULTS: Twenty-three of 27 patients achieved complete remission (CR). With a median follow-up time of 70 months (range, 32 to 214 months), overall survival to date is 100%, and overall event-free survival (EFS) is 69% +/- 10% (SA, 42% +/- 16%; CT, 90% +/- 8.6%; P <.04). If we considered only the patients in CR after initial surgery (n = 12), EFS was no longer significantly different between the two groups. Patients with residual mass after initial surgery (n = 15) had worse EFS if they did not receive complementary treatment (P <.05). CONCLUSION: Although based on a small number of patients, our study showed that (1). no further therapy is a valid therapeutic approach in LPHL patient in CR after initial lymph node resection, and (2). complementary treatment diminishes relapse frequency but has no impact on survival.
Assuntos
Doença de Hodgkin/terapia , Excisão de Linfonodo , Adolescente , Criança , Pré-Escolar , Terapia Combinada , Feminino , Doença de Hodgkin/patologia , Humanos , Masculino , Recidiva Local de Neoplasia , Estudos Prospectivos , Indução de Remissão , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: To evaluate growth, thyroid function, puberty, cardiac function, and the incidence of cataracts in children who received allogeneic bone marrow transplantation (BMT) for acute myeloblastic leukemia (AML) in first complete remission (CR) after a preparation with or without total-body irradiation (TBI). PATIENTS AND METHODS: Among 45 children studied, 26 received busulfan-cyclophosphamide (Bu-Cy) in preparation for transplantation and 19 received TBI. TBI was fractionated in nine cases and delivered as a single dose in 10. Four children in the Bu-Cy group and none in the TBI group had received prior cranial radiation. The mean follow-up duration after BMT was 5.9 years for the whole group. RESULTS: The mean cumulative changes in height SD score (SDS) were -0.86 at 3 years and -1.56 at 5 years in the TBI group, whereas these changes were only -0.05 and -0.17 in the Bu-Cy group (P < .01 at 3 and 5 years). The 6-year probability of hypothyroidism was 9% +/- 8% in the Bu-Cy group and 43% +/- 15% after TBI (P < .02). Pubertal development after Bu-Cy was assessable in two girls and five boys: both girls had primary ovarian failure, whereas Leydig cell function appeared to be preserved in the five boys. One child who had received anthracycline when he was less than 1 year old developed cardiac dysfunction 4 years after Bu-Cy. The 6-year probability of cataracts was 70% +/- 13% in the TBI group and 0% after Bu-Cy. CONCLUSION: The use of Bu-Cy represents an alternative transplant cytoreductive regimen for children with AML in first CR, which can reduce the risk of posttransplant growth impairment, thyroid dysfunction, Leydig cell damage, and the incidence of cataracts.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Leucemia Mieloide Aguda/terapia , Puberdade/efeitos dos fármacos , Condicionamento Pré-Transplante/métodos , Adolescente , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Feminino , Crescimento/efeitos dos fármacos , Crescimento/efeitos da radiação , Humanos , Lactente , Leucemia Mieloide Aguda/radioterapia , Masculino , Irradiação Corporal TotalRESUMO
UNLABELLED: Evans' Syndrome (ES) is defined as the combination of immune thrombocytopenia (ITP) and autoimmune haemolytic anemia (AIHA), in the absence of any known underlying etiology. Pathophysiology, epidemiology and outcome remain unclear. POPULATION: Thirty-six children (20 male, 16 female), who were diagnosed in the SHIP french centres (Société d'hématologie et d'immunologie pédiatrique) between 1990 and 2002 with ES, were included in this retrospective study. RESULTS: Median age at diagnosis was 4 years. In 21 children, ES occurred in the setting of consanguinity, family history of autoimmune/inflammatory disease, associated autoimmune disorder or immunoregulatory abnormalities (serum imunoglobulins, peripheral blood lymphocytes subsets, low level of the C3-C4 complement components, nuclear antibodies). Several successive treatments were used in this serie (median: 3, range: 0-10) including corticosteroid therapy (35/36), intravenous immunoglobulins (32/36), immunosuppressive agents (14/36), splenectomy (9/36) and anti CD 20 monoclonal antibodies (6/36). Patients with a low level of serum immunoglobulins were more often non-responders to corticosteroidtherapy/intravenous immunoglobulins and required more frequently further therapy (P=0.03). Three patients died (intracranial bleeding, N=2, Guillain-Barre syndrome; N=1). CONCLUSION: ES was a severe, life-threatening disease, requiring aggressive immunosuppressive therapy in as many as half the patients. Our forthcoming study aims to (i) describe homogeneously-studied and prospectively-analysed cohort of childhood ES, (ii) separate ES from specific immune deficiency (especially fas gene mutations), generalised autoimmune/inflammatory disorders and genetic diseases, (iii) identify well-defined ES subsets, (iv) establish prognostic factors and optimal treatment within these subsets.
Assuntos
Anemia Hemolítica Autoimune/patologia , Púrpura Trombocitopênica Idiopática/patologia , Adolescente , Corticosteroides/uso terapêutico , Idade de Início , Anemia Hemolítica Autoimune/tratamento farmacológico , Anemia Hemolítica Autoimune/genética , Anemia Hemolítica Autoimune/imunologia , Criança , Pré-Escolar , Estudos de Coortes , Consanguinidade , Feminino , França , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Masculino , Prognóstico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/genética , Púrpura Trombocitopênica Idiopática/imunologia , Estudos Retrospectivos , Índice de Gravidade de Doença , SíndromeRESUMO
OBJECTIVE: To assess the efficacy of combination therapy that includes ritonavir in HIV-1 infected children. DESIGN: A monocentric retrospective study. PATIENTS AND METHODS: Twenty-two children with a minimum follow-up of 6 months under triple therapy including ritonavir were analysed for treatment efficacy. At entry, all the patients were protease inhibitor naive and all but two had received previous antiretroviral therapy during a median period of 5 years. Their initial median CD4+ lymphocyte count and viral load were 121 x 10(6)/l and 5.08 log10 copies/ml, respectively. Clinical and biological evaluation included clinical assessment every 6 weeks and determination of CD4 cell count and HIV-RNA concentration every 3 months. RESULTS: Median length of follow-up on triple therapy was 15 months (range: 7-21 months). Neither progression in the CDC classification nor death occurred. No significant change in mean weight SD scores was noted when baseline values were compared with values obtained after 1 year of triple therapy. Median CD4 count increases were of 210 x 10(6)/l, 415 x 10(6)/l, and 472 x 10(6)/l cells at 6, 12, and 18 months, respectively. Among the patients baseline characteristics, neither age nor initial CD4 cells count influenced the magnitude of immunologic improvement. There were median decreases of 1.14, 0.95, and 1.5 log10 per ml of plasma in the concentration of viral RNA at 6, 12, and 18 months respectively. Seven patients maintained an undetectable viral load when under treatment. The introduction of at least one new reverse transcriptase inhibitor at the initiation of triple therapy correlated significantly with a greater viral suppression. CONCLUSION: Despite variable viral response, antiretroviral-experienced HIV-infected children demonstrated a substantial CD4 cell increase during a median period of 15 months of ritonavir containing combination therapy.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Ritonavir/uso terapêutico , Adolescente , Fármacos Anti-HIV/efeitos adversos , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Seguimentos , Infecções por HIV/imunologia , Infecções por HIV/virologia , Inibidores da Protease de HIV/efeitos adversos , Humanos , Lamivudina/efeitos adversos , Lamivudina/uso terapêutico , Masculino , Inibidores da Transcriptase Reversa/efeitos adversos , Ritonavir/efeitos adversos , Estavudina/efeitos adversos , Estavudina/uso terapêutico , Zidovudina/efeitos adversos , Zidovudina/uso terapêuticoRESUMO
Although clinical experience and in vitro data provide evidence of an anti-leukemic activity of T cells, there are few examples of recognition of leukemic cells by tumor-specific T cells in vitro. Tumor antigens encoded by the MAGE genes are useful tools to study this recognition. We tested the sensitivity to recognition and lysis by anti-MAGE CTL clones of MAGE-A1 positive cell lines HL60 and K562, after transfection with an HLA-A1 construct, and of fresh leukemic blasts from 10 HLA-A2 patients, after incubation with a peptide encoded by gene MAGE-A3. The presentation of MAGE antigens by leukemic cell lines and fresh leukemic blasts induced TNF secretion and cytotoxicity by MAGE-specific CD8(+) CTL clones. The amount of peptide presented by the leukemic blasts, more than the level of expression of HLA class I, adhesion or costimulatory molecules, was the major limiting factor for recognition. These data indicate that leukemic cells may be targeted by T cells showing specificity for a leukemia antigen.
Assuntos
Leucemia/imunologia , Linfócitos T Citotóxicos/imunologia , Antígenos de Neoplasias , Células HL-60 , Antígeno HLA-A1/fisiologia , Antígeno HLA-A2/fisiologia , Humanos , Células K562 , Antígenos Específicos de Melanoma , Proteínas de Neoplasias/imunologia , TransfecçãoRESUMO
We report a clinically isolated toxoplasma pneumonitis in a child treated by HLA haplo-mismatched BMT. Conditioning consisted of TBI, cytarabine and melphalan. The BM graft was T-depleted and the boy received iv moAb antiLFA1 and antiCD2. The clinical course of pneumonitis was characterised by an early onset (day 28) and a rapidly overwhelming course. Donor and recipient had pre-graft IgG Ab against toxoplasma without IgM. These Abs had completely disappeared from the serum of the patient at the time of pneumonitis. PCR amplification detected the B1 gene of Toxoplasma gondii in the patient's PBMC from day 28.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Pneumopatias Parasitárias/etiologia , Toxoplasmose/etiologia , Animais , Pré-Escolar , Teste de Histocompatibilidade , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Transplante HomólogoRESUMO
We evaluated the long-term side-effects of allogeneic BMT performed early in the course of childhood acute leukaemia (first complete remission and interval between diagnosis and BMT not exceeding 6 months). Thirteen patients fulfilled these criteria. Conditioning regimens included TBI in eight cases. Evaluation of growth and pubertal development, ophthalmological examination, assessment of thyroid, cardiac and pulmonary functions were performed. Neuropsychological evaluation included IQ score, memory tests and cranial MRI. Median follow-up after BMT was 5 years (range 2-10 years). Growth was normal in seven patients. Six patients experienced a decrease in SD score for height (range -0.1 to -1.9). Four children were evaluable for puberty: pubertal development was normal in three children and delayed in one case. Thyroid and left ventricular function were normal in all cases. Three patients had mild abnormalities of pulmonary function. In two patients cataracts were noted 7 and 10 years after fTBI. Mean full-scale IQ score was 102. Memory tests, performed in 12 cases, were in the normal range for 11 patients. In our study, frequency and severity of long-term side-effects following BMT for leukemia appeared lower than usually reported. A possible explanation is that children were transplanted very early in the course of their disease with neither cranial irradiation nor long exposure to chemotherapy prior to transplant.
Assuntos
Transplante de Medula Óssea , Leucemia Mieloide/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Doença Aguda , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Crescimento , Humanos , Lactente , Leucemia Mieloide/fisiopatologia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologia , Puberdade/fisiologia , Indução de Remissão , Taxa de Sobrevida , Transplante HomólogoRESUMO
We report the outcome of 12 children who underwent unrelated cord blood transplant (U-CBT) in a single institution between February 1997 and July 1998. The 1 year event-free survival was 67% (95% CI of 26%). Four children died with infectious complication as cause of death in three cases. Immune reconstitution was studied during first year post transplant by assaying total lymphocyte counts, B cells, NK cells and T cell subsets in the eight disease-free surviving patients. We observed a prompt recovery of CD19+ cell number which was greater than 500/microl at 9 months for all patients except the one with severe cGVHD. B cells constituted the predominant lymphocyte subset at 6 and 9 months post transplant with normal or elevated B cell numbers according to normal paediatric range. We noted normal serum immunoglobulin levels at 6 months post transplant for IgA and IgM and at 9 months for IgG. The CD3+ cell count and particularly the CD3+CD8+ T cell subset remained depressed until 12 months post transplant. Six months after unrelated CBT, seven out of eight patients had less than 100 CD3+CD8+ cells/microl. CD3+CD4+ cell recovery was less impaired with all children achieving an absolute count of CD3+CD4+ cells greater than 200/microl during the first year in a median of 5 months. The percentage of NK cells was elevated during the first 6 months after CBT but their absolute count remained within the normal range. Bone Marrow Transplantation (2000) 25, 53-57.
Assuntos
Sangue Fetal , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Imunidade , Adolescente , Criança , Pré-Escolar , Transplante de Tecido Fetal , Teste de Histocompatibilidade , Humanos , Lactente , Transplante HomólogoRESUMO
INTRODUCTION: The Comoro archipelago is characterised by a high prevalence of red cell genetic disorders such as G6PD deficiency and haemoglobinopathies, being a region endemic for malaria. Over the last 15 years, the city of Marseilles in France has become the main destination for Comorian immigrants. This Comorian community includes patients with sickle cell disease, sickle cell/beta-thalassaemia trait, thalassaemias and G6PD deficiency. MATERIALS AND METHODS: Allele frequencies for haemoglobin S, beta-thalassaemia and G6PD deficiency were determined from neonatal and prenatal screenings of the Comorian community. Haemoglobin fractions were detected by isoelectrofocalisation, and the quantitation of HbS, HbA, HbA(2) and HbF was performed by cation exchange high performance liquid chromatography. The molecular study involved 31 alleles carrying the betaS mutation (Cd 6 [A-->T]), six beta-thalassaemic alleles and 17 G6PD-deficient alleles, selected from a group of carriers or affected subjects. RESULTS: Allele frequencies were 3% for haemoglobin S, 1% for beta-thalassaemia trait and 9.5% for G6PD deficiency. Molecular analysis had revealed that the African alleles are predominant, being present in almost all the subjects studied. Mediterranean alleles were found for all the beta-thalassaemia mutations and for three G6PD chromosomes out of 17. CONCLUSION: These data are consistent with the mixed Arab and African origin of the population of the Comoro Islands, and are of clinical interest in prenatal and newborn screening plans.