RESUMO
OBJECTIVE: To obtain a national overview of the epidemiology and management of invasive fungal infections (IFIs) in France for severely immunocompromised children who were treated for acute leukemia or had undergone allogeneic hematopoietic stem cell transplantation (a-HSCT). STUDY DESIGN: We performed a national multicenter retrospective study to collect epidemiologic data for proven and probable IFIs in children with acute leukemia under first- line or relapse treatment or who had undergone a-HSCT. We also conducted a prospective practice survey to provide a national overview of IFI management in pediatric hematology units. RESULTS: From January 2014 to December 2017, 144 cases of IFI were diagnosed (5.3%) in 2721 patients, including 61 cases of candidiasis, 60 cases of aspergillosis, and 23 cases of infection with "emergent" fungi, including 10 cases of mucormycosis and 6 cases of fusariosis. The IFI rate was higher in patients with acute myelogenous leukemia (12.9%) (OR, 3.24; 95% CI, 2.15-4.81; P < .0001) compared with the rest of the cohort. Patients undergoing a-HSCT had an IFI rate of only 4.3%. In these patients, the use of primary antifungal prophylaxis (principally fluconazole) was associated with a lower IFI rate (OR, 0.28; 95% CI, 0.14-0.60; P = 4.90 ×10-4) compared with a-HSCT recipients who did not receive antifungal prophylaxis. The main cause of IFI in children receiving prophylaxis was emergent pathogens (41%), such as mucormycosis and fusariosis, which were resistant to the prophylactic agents. CONCLUSIONS: The emerging fungi and new antifungal resistance profiles uncovered in this study should be considered in IFI management in immunocompromised children.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Hospedeiro Imunocomprometido , Infecções Fúngicas Invasivas/epidemiologia , Leucemia Mieloide Aguda/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Adolescente , Criança , Pré-Escolar , Feminino , França , Humanos , Incidência , Lactente , Recém-Nascido , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/terapia , Masculino , Estudos RetrospectivosRESUMO
OBJECTIVE: To describe 4 subgroups of pediatric patients treated with splenectomy, hydroxychloroquine, azathioprine, or rituximab as the first-option, second-line treatment for chronic immune thrombocytopenia. STUDY DESIGN: Selection of patients with chronic immune thrombocytopenia from the French national prospective cohort of pediatric autoimmune cytopenia OBS'CEREVANCE and VIGICAIRE study, treated by splenectomy, hydroxychloroquine, azathioprine, or rituximab as a first second-line treatment. RESULTS: For 137 patients, treated between 1989 and 2016, the median follow-up after diagnosis and after treatment initiation was 8.5 (2.8-26.4) years and 4.7 (1.1-25.1) years, respectively. Median age at diagnosis and at initiation of treatment were 9 (0.7; 16) and 12 (2; 18.1) years, respectively without significant difference between subgroups. For the whole cohort, 24-month event-free survival was 62% (95% CI 55; 71). It was 85% (95% CI 77; 95) for the 56 patients treated with splenectomy, 60% (95% CI 44; 84) for the 23 patients treated with rituximab, 46% (95% CI 30; 71) for the 24 patients treated with azathioprine, and 37% (95% CI 24; 59) for the 34 patients treated with hydroxychloroquine (log-rank P < .0001). For the splenectomy subgroup, being older than 10 years at splenectomy tended to improve event-free survival (P = .05). Female teenagers with antinuclear antibody positivity benefited from hydroxychloroquine therapy. CONCLUSIONS: This national study, limiting pitfalls in the analysis of the effects of second-line therapies, showed that splenectomy remains the treatment associated with the better response at 24 months.
Assuntos
Azatioprina/uso terapêutico , Hidroxicloroquina/uso terapêutico , Imunomodulação , Púrpura Trombocitopênica Idiopática/terapia , Rituximab/uso terapêutico , Esplenectomia , Adolescente , Criança , Pré-Escolar , Doença Crônica , Feminino , Humanos , Lactente , Masculino , Estudos ProspectivosRESUMO
OBJECTIVE: To evaluate the association between medical and social environmental factors and the risk of repeating a grade in childhood leukemia survivors. STUDY DESIGN: A cross-sectional study of childhood leukemia survivors, recruited through the LEA cohort (Leucémie de l'Enfant et de l'Adolescent [French Childhood Cancer Survivor Study for Leukemia]) in 2014. An adjusted logistic regression model was used to identify variables linked to repeating a grade after the diagnosis among the survivors, and the rates of repeating a grade were compared between the survivors and their siblings using a multilevel logistic regression model. RESULTS: The mean age at inclusion of the 855 participants was 16.2 ± 7.0 years, and the mean duration of follow-up from diagnosis to evaluation was 10.2 ± 6.2 years. After disease onset, 244 patients (28.5%) repeated a grade, with a median interval of 4 years (IQR, 2-8 years). Independent factors associated with repeating a grade were male sex (OR, 1.78; 95% CI, 1.21-2.60), adolescence (OR, 2.70; 95% CI, 1.63-4.48), educational support during the treatment period (OR, 3.79; 95% CI, 2.45-5.88), low parental education level (OR, 2.493; 95% CI, 1.657-3.750), and household financial difficulties (OR, 2.62; 95% CI, 1.607-4.28). Compared with siblings, survivors were at greater risk of repeating a grade (OR, 1.87; 95% CI, 1.48-2.35). CONCLUSIONS: The most vulnerable patients seemed to be adolescents and those with parents of low socioeconomic status. Improving the schooling career of leukemia survivors will require that the medical community more carefully consider the social status of patients.
Assuntos
Previsões , Nível de Saúde , Leucemia/epidemiologia , Qualidade de Vida , Medição de Risco/métodos , Adolescente , Criança , Estudos Transversais , Feminino , Seguimentos , França/epidemiologia , Humanos , Incidência , Masculino , Fatores de Risco , Fatores Socioeconômicos , Taxa de Sobrevida/tendências , Adulto JovemRESUMO
OBJECTIVE: To study the risk of catheter-associated thrombosis (CAT) between peripherally inserted central catheters (PICCs) and tunneled central venous catheters in children with leukemia. STUDY DESIGN: We analyzed all PICCs and conventional tunneled catheters placed in patients aged <18 years and admitted to our institute for leukemia treatment between February 2008 and April 2014. Cases of symptomatic CAT were confirmed by ultrasound and treated with low-molecular-weight heparin. RESULTS: During the study period, 157 PICCs and 138 conventional tunneled catheters were placed in 192 patients with leukemia. CAT incidence was 1.5% (n = 2) in the conventional tunneled catheter group and 10.2% (n = 16) in the PICC group. The OR for CAT occurrence after PICC vs conventional tunneled catheter placement was 5.6 (95% CI, 1.2-26.5). CONCLUSION: Our results suggest that the use of PICCs in children with leukemia increases the risk of CAT in comparison with the use of conventional tunneled catheters. Further randomized controlled studies are needed to characterize this risk and to better define indications.
Assuntos
Cateterismo Venoso Central/efeitos adversos , Cateterismo Periférico/efeitos adversos , Cateterismo Periférico/instrumentação , Cateteres Venosos Centrais/efeitos adversos , Leucemia/terapia , Trombose Venosa/epidemiologia , Criança , Feminino , Humanos , Incidência , Masculino , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVES: To investigate the associations between several sickle cell disease genetic modifiers (beta-globin haplotypes, alpha-thalassemia, and glucose-6-phosphate dehydrogenase deficiency) and the level of oxidative stress and to evaluate the association between oxidative stress and the rates of vaso-occlusive events. STUDY DESIGN: Steady-state oxidative and nitrosative stress markers, biological variables, genetic modulators, and vaso-occlusive crisis events requiring emergency admissions were measured during a 2-year period in 62 children with sickle cell anemia (58 SS and 4 Sß0). Twelve ethnic-matched children without sickle cell anemia also participated as healthy controls (AA) for oxidative and nitrosative stress level measurement. RESULTS: Oxidative and nitrosative stress were greater in patients with sickle cell anemia compared with control patients, but the rate of vaso-occlusive crisis events in sickle cell anemia was not associated with the level of oxidative stress. The presence of alpha-thalassemia, but not glucose-6-phosphate dehydrogenase deficiency or beta-globin haplotype, modulated the level of oxidative stress in children with sickle cell anemia. CONCLUSION: Mild hemolysis in children with alpha-thalassemia may limit oxidative stress and could explain the protective role of alpha-thalassemia in hemolysis-related sickle cell complications.
Assuntos
Anemia Falciforme/genética , Anemia Falciforme/fisiopatologia , Predisposição Genética para Doença , Estresse Oxidativo , Índice de Gravidade de Doença , Adolescente , Anemia Falciforme/diagnóstico , Criança , Pré-Escolar , Feminino , Seguimentos , Marcadores Genéticos , Humanos , Modelos Lineares , Masculino , Estudos Retrospectivos , Fatores de RiscoRESUMO
Umbilical cord blood (UCB) from an human leucocyte antigen (HLA)-identical sibling can be used for transplantation of patients with malignant and non-malignant diseases. However, the low cellular content of most UCB units represents a limitation to this approach. An option to increase cell dose is to harvest bone marrow (BM) cells from the same donor and infuse them along with the UCB. We studied 156 children who received such a combined graft between 1992 and 2011. Median age was 7 years and 78% of patients (n = 122) were transplanted for non-malignant diseases, mainly haemoglobinopathies. Acute leukaemia (n = 26) was the most frequent malignant diagnosis. Most patients (91%) received myeloablative conditioning. Median donor age was 1·7 years, median infused nucleated cell dose was 24·4 × 10(7) /kg and median follow-up was 41 months. Sixty-days neutrophil recovery occurred in 96% of patients at a median of 17 d. The probabilities of grade-II-IV acute and chronic graft-versus-host disease (GVHD) were 19% and 10%, respectively. Four-year overall survival was 90% (68% malignant; 97% non-malignant diseases) with 3% probability of death. In conclusion, combined UCB and BM transplantation from an HLA-identical sibling donor is an effective treatment for children with malignant and non-malignant disorders with high overall survival and low incidence of GVHD.
Assuntos
Transplante de Medula Óssea , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/terapia , Leucemia/mortalidade , Leucemia/terapia , Condicionamento Pré-Transplante , Doença Aguda , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Doença Crônica , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Humanos , Lactente , Doadores Vivos , Masculino , Taxa de SobrevidaRESUMO
Neuropilins and semaphorins are known as modulators of axon guidance, angiogenesis, and organogenesis in the developing nervous system, but have been recently evidenced as also playing a role in the immune system. Here we describe the expression and role of semaphorin 3F (SEMA3F) and its receptor neuropilin-2 (NRP2) in human T cell precursors. NRP2 and SEMA3F are expressed in the human thymus, in both lymphoid and non-lymphoid compartments. SEMA3F have a repulsive effect on thymocyte migration and inhibited CXCL12- and sphingosine-1-phosphate (S1P)-induced thymocyte migration by inhibiting cytoskeleton reorganization prior to stimuli. Moreover, NRP2 and SEMA3F are expressed in human T-cell acute lymphoblastic leukemia/lymphoma primary cells. In these tumor cells, SEMA3F also blocks their migration induced by CXCL12 and S1P. Our data show that SEMA3F and NRP2 are further regulators of human thymocyte migration in physiological and pathological conditions.
Assuntos
Movimento Celular/genética , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Neuropilina-2/genética , Células Precursoras de Linfócitos T/metabolismo , Anticorpos Bloqueadores/imunologia , Anticorpos Bloqueadores/farmacologia , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Quimiocina CXCL12/farmacologia , Criança , Pré-Escolar , Expressão Gênica , Humanos , Lactente , Recém-Nascido , Lisofosfolipídeos/farmacologia , Proteínas de Membrana/metabolismo , Proteínas de Membrana/farmacologia , Microscopia Confocal , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/farmacologia , Neuropilina-2/imunologia , Neuropilina-2/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Esfingosina/análogos & derivados , Esfingosina/farmacologia , Timócitos/metabolismo , Timo/citologia , Timo/metabolismoRESUMO
Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a rare immunodeficiency disorder. We report three patients with WHIM syndrome who are affected by Tetralogy of Fallot (TOF). This observation suggests a possible increased risk of TOF in WHIM syndrome and that birth presentation of TOF and neutropenia should lead to suspect WHIM syndrome.
Assuntos
Síndromes de Imunodeficiência/complicações , Tetralogia de Fallot/etiologia , Verrugas/complicações , Adolescente , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/tratamento farmacológico , Síndromes de Imunodeficiência/genética , Masculino , Mutação , Linhagem , Doenças da Imunodeficiência Primária , Receptores CXCR4/genética , Tetralogia de Fallot/genética , Verrugas/diagnóstico , Verrugas/tratamento farmacológico , Verrugas/genética , Adulto JovemRESUMO
OBJECTIVE: To evaluate the effect of bone marrow transplantation in children with Hunter syndrome. STUDY DESIGN: Eight boys received a bone marrow graft between the ages of 3 and 16 years from 1990 to 2000. In 6 cases, the donor was a sibling with identical HLA status, in 1 case an unrelated donor with HLA-compatible, and in 1 case a mismatched unrelated donor. A complete multidisciplinary evaluation was performed yearly. RESULTS: Successful engraftment was achieved in all patients, with the proportion of donor cells reaching > or =95% 1 month after transplantation in all patients. Patients have been followed from between 7 and 17 years and all are still alive, except for 1 boy who died at the age of 10 from unrelated causes. Cardiovascular abnormalities stabilized in all patients, hepatosplenomegaly resolved, and joint stiffness improved, Perceptual hearing defects remained stable, and transmission hearing defects improved. Only 1 child required subsequent surgery to correct kyphosis. Neuropsychological outcome was variable and appeared to be related to the severity of the syndrome. CONCLUSIONS: Bone marrow transplantation is effective on the no neuropsychological symptoms of Hunter disease.