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1.
Haematologica ; 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33440924

RESUMO

Pediatric-onset Evans syndrome (pES) is defined by both immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA) before the age of 18 years. There have been no comprehensive long-term studies of this rare disease, which can be associated to various immunopathological manifestations (IMs). We report outcomes of the 151 patients with pES and more than 5 years of follow-up from the nationwide French prospective OBS'CEREVANCE cohort. Median age at final follow-up was 18.5 (6.8-50.0) years and the median follow-up period was 11.3 (5.1-38.0) years. At 10 years, ITP and AIHA were in sustained complete remission in 54.5% and 78.4% of patients, respectively. The frequency and number of clinical and biological IMs increased with age: at 20 years old, 74% had at least one clinical cIM. A wide range of cIMs occurred, mainly lymphoproliferation, dermatological, gastrointestinal/hepatic and pneumological IMs. The number of cIMs was associated with a subsequent increase in the number of second-line treatments received (other than steroids and immunoglobulins; hazard ratio, 1.4; 95% confidence interval, 1.15-1.60; p = 0.0002, Cox proportional hazards method). Survival at 15 years after diagnosis was 84%. Death occurred at a median age of 18 (1.7-31.5) years, and the most frequent cause was infection. The number of second-line treatments and severe/recurrent infections were independently associated with mortality. In conclusion, longterm outcomes of pES showed remission of cytopenias but frequent IMs linked to high secondline treatment burden. Mortality was associated to drugs and/or underlying immunodeficiencies, and adolescents-young adults are a high-risk subgroup.

2.
Clin Nucl Med ; 45(1): e67-e68, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31348082

RESUMO

A 17-year-old girl underwent an F-DOPA brain PET/CT on a new high-resolution digital SiPM PET/CT (Vision600 Siemens) to explore a suspicion of recurrence of a pilocytic astrocytoma. This study showed a local recurrence, but a second intense focal uptake was visible above, more intense than striata. On fused MRI, this was the pineal gland considered as physiological. This physiological uptake, due to a pineal DOPA decarboxylase activity, has also been observed with this PET system in other patients with F-DOPA to explore movement disorders. New high-resolution PET can show uptake of small structures by being less dependent to partial volume effect.


Assuntos
Di-Hidroxifenilalanina/análogos & derivados , Glândula Pineal/diagnóstico por imagem , Glândula Pineal/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Adolescente , Astrocitoma/diagnóstico por imagem , Astrocitoma/patologia , Transporte Biológico , Di-Hidroxifenilalanina/metabolismo , Feminino , Humanos
3.
Biol Blood Marrow Transplant ; 25(4): 734-742, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30385256

RESUMO

We previously reported in a French prospective randomized study that transplantation of 2 unrelated cord blood (UCB) units instead of 1 unit does not decrease the risk of transplantation failure but may enhance alloreactivity. Here we evaluated the influence of pretransplantation minimal residual disease (MRD) on leukemia relapse and survival after single- versus double-UCB transplantation (UCBT). Among 137 children and young adults who underwent UCBT in this randomized study, 115 had available data on MRD assessment done immediately before initiation of the pretransplantation conditioning regimen. MRD was considered positive at a level of ≥10-4, which was the case of 43 out of 115 patients. Overall, the mean 3-year survival probability was 69.1 ± 4.4%, and it was not significantly influenced by the MRD level: 70.7 ± 5.4% in MRD-negative (<10-4) patients (n = 72), 71.1 ± 9.4% in MRD-positive patients with 10-4 ≤ MRD <10-3 (n = 26) and 58.8 ± 11.9% in MRD-positive patients with ≥10-3 (n = 17). In the MRD-positive group, the mean risk of relapse was significantly lower in the double-UCBT arm compared with the single-UCBT arm (10.5 ± 7.2% versus 41.7 ± 10.4%; P = .025) leading to a higher mean 3-year survival rate (82.6 ± 9.3% versus 53.6 ± 10.3%; P = .031). This difference was observed only in patients who had not received antithymocyte globulin during their conditioning regimen. In the MRD-negative group, there was no differencebetween the single- and the double-UCBT arms. We conclude that even in cases of positive pretransplantation MRD, UCBT in children and young adults with acute leukemia yields a high cure rate, and that a double-unit strategy may enhance the graft-versus-leukemia effect and survival in these patients.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Leucemia Mieloide Aguda/terapia , Adulto , Feminino , Humanos , Masculino , Estudos Prospectivos , Adulto Jovem
4.
Fundam Clin Pharmacol ; 32(3): 337-342, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29319893

RESUMO

Ifosfamide (IFA) is a potent alkylating antitumoral agent, but its use is limited by neurological side effects. IFA is a racemic mixture of two enantiomeric forms, R-IFA and S-IFA with a stereoselective metabolism by CYP3A4 and CYP2B6, leading either to bioactive or to toxic pathways. In three consecutive cases of pediatric patients who exhibited IFA-induced encephalopathy (IIE), genotyping of clinically relevant single-nucleotide polymorphisms associated with decreased CYP3A4 and CYP2B6 activities was performed. Genetic investigations revealed the presence of CYP2B6 rs4803419 (C>T) in one patient while the two others carried the CYP2B6*6 allelic variant. All patients carried CYP3A4 wild-type genotype (CYP3A4*1/*1). Because CYP2B6-deficient alleles may be responsible for an increased conversion of S-IFA into neurotoxic metabolites, screening for CYP2B6 polymorphisms may help to avoid IIE and improve clinical outcomes.


Assuntos
Antineoplásicos Alquilantes/efeitos adversos , Neoplasias Ósseas/tratamento farmacológico , Encefalopatias/induzido quimicamente , Encefalopatias/genética , Citocromo P-450 CYP2B6/genética , Ifosfamida/efeitos adversos , Osteossarcoma/tratamento farmacológico , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Administração Intravenosa , Adolescente , Antineoplásicos Alquilantes/metabolismo , Encefalopatias/diagnóstico , Encefalopatias/tratamento farmacológico , Criança , Citocromo P-450 CYP2B6/metabolismo , Feminino , Predisposição Genética para Doença , Humanos , Ifosfamida/metabolismo , Masculino , Azul de Metileno/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Farmacogenética , Fenótipo , Fatores de Risco , Resultado do Tratamento
5.
J Hematol Oncol ; 10(1): 102, 2017 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-28482908

RESUMO

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT), the most widely used potentially curable cellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening complications: graft versus host disease (GVHD) and infections especially viral infections refractory to antiviral drugs. Adoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We report here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell (ADV-VST) infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted with umbilical cord blood (UCB). METHODS: Fourteen patients were eligible and 11 patients received infusions of ADV-VST generated by interferon (IFN)-γ-based immunomagnetic isolation from a leukapheresis from their original donor (42.9%) or a third party haploidentical donor (57.1%). One patient resolved ADV infection before infusion, and ADV-VST could not reach release or infusion criteria for two patients. Two patients received cellular immunotherapy alone without antiviral drugs as a pre-emptive treatment. RESULTS: One patient with adenovirus infection and ten with adenovirus disease were infused with ADV-VST (mean 5.83 ± 8.23 × 103 CD3+IFN-γ+ cells/kg) up to 9 months after transplantation. The 11 patients showed in vivo expansion of specific T cells up to 60 days post-infusion, associated with adenovirus load clearance in ten of the patients (91%). Neither de novo GVHD nor side effects were observed during the first month post-infusion, but GVHD reactivations occurred in three patients, irrespective of the type of leukapheresis donor. For two of these patients, GVHD reactivation was controlled by immunosuppressive treatment. Four patients died during follow-up, one due to refractory ADV disease. CONCLUSIONS: Adoptive transfer of rapidly isolated ADV-VST is an effective therapeutic option for achieving in vivo expansion of specific T cells and clearance of viral load, even as a pre-emptive treatment. Our study highlights that third party haploidentical donors are of great interest for ADV-VST generation in the context of UCB transplantation. (N° Clinical trial.gov: NCT02851576, retrospectively registered).


Assuntos
Infecções por Adenovirus Humanos/terapia , Adenovírus Humanos/imunologia , Imunoterapia Adotiva/métodos , Subpopulações de Linfócitos T/transplante , Viremia/terapia , Infecções por Adenovirus Humanos/sangue , Infecções por Adenovirus Humanos/prevenção & controle , Adolescente , Adulto , Aloenxertos , Criança , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Humanos , Separação Imunomagnética , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Interferon gama/metabolismo , Leucaférese , Masculino , Especificidade do Receptor de Antígeno de Linfócitos T , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Doadores de Tecidos , Transplante Haploidêntico , Resultado do Tratamento , Carga Viral , Ativação Viral , Adulto Jovem
6.
Br J Haematol ; 177(5): 751-758, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28444729

RESUMO

Childhood autoimmune haemolytic anaemia (AIHA) requires second-line immunosuppressive therapy in 30-50% of cases. It appears that rituximab is indicated in such circumstances. This prospective national study reports the practice, efficacy and tolerance of rituximab in children with isolated AIHA and AIHA in the setting of Evans syndrome (ES). Sixty-one children were given rituximab between 2000 and 2014. The median interval from diagnosis to rituximab was 9·9 [interquartile range (IQR) 1·6-28·5] months. Forty-six patients responded (75%) and the 6-year relapse-free survival (RFS) was 48%. Twenty patients relapsed at a median interval of 10·8 (IQR 3·9-18·7) months, rituximab allowed steroid withdrawal in 44/61 (72%) of children. In isolated AIHA, complete response and 6-year RFS were significantly higher than in ES (P < 0·05). Ten out of 61 patients were infants, seven of who responded with a 6-year RFS of 71%. Among patients without immunoglobulin substitution before rituximab, 4 are still receiving substitutions. Five patients died, including one potentially attributable to rituximab. This large observational series of childhood AIHA established the rituximab benefit-risk ratio, allowing steroid withdrawal, with 37% of long-term responders, mainly in isolated AIHA. All subgroups of patients drew benefit. Our long-term results indicate the baseline to be challenged by new treatment approaches.


Assuntos
Anemia Hemolítica Autoimune/tratamento farmacológico , Hematínicos/uso terapêutico , Rituximab/uso terapêutico , Adolescente , Transfusão de Sangue/estatística & dados numéricos , Criança , Pré-Escolar , Substituição de Medicamentos , Feminino , França , Humanos , Masculino , Estudos Prospectivos , Esteroides/uso terapêutico , Resultado do Tratamento
7.
Blood ; 127(26): 3450-7, 2016 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-27099151

RESUMO

Transplantation of 2 unrelated cord blood (UCB) units instead of 1 has been proposed to increase the cell dose. We report a prospective randomized study, designed to compare single- vs double-UCB transplantation in children and young adults with acute leukemia in remission or myelodysplasia. Eligible patients had at least two 4-6 HLA-identical UCBs with >3 × 10(7) nucleated cells/kg for the first and >1.5 × 10(7) for the second. The primary end point was the 2-year cumulative incidence of transplantation strategy failure, a composite end point including transplant-related mortality (TRM), engraftment failure, and autologous recovery. Randomized patients who did not proceed to transplantation due to refractory disease were considered transplantation failures. A total of 151 patients were randomized and included in the intent-to-treat analysis; 137 were transplanted. Double-UCB transplantation did not decrease transplantation strategy failure (23.4% ± 4.9% vs 14.9% ± 4.2%). Two-year posttransplant survival, disease-free survival, and TRM were 68.8% ± 6.0%, 67.6% ± 6.0%, and 5.9% ± 2.9% after single-unit transplantation compared with 74.8% ± 5.5%, 68.1% ± 6.0%, and 11.6% ± 3.9% after double-unit transplantation. The final relapse risk did not significantly differ, but relapses were delayed after double-unit transplantation. Overall incidences of graft-versus-host disease (GVHD) were similar, but chronic GVHD was more frequently extensive after double-UCB transplantation (31.9% ± 5.7% vs 14.7% ± 4.3%, P = .02). In an exploratory subgroup analysis, we found a significantly lower relapse risk after double-unit transplantation in patients receiving total body irradiation without antithymocyte globulin (ATG), whereas the relapse risk was similar in the group treated with busulfan, cyclophosphamide, and ATG. Single-UCB transplantation with adequate cell dose remains the standard of care and leads to low TRM. Double-unit transplantation should be reserved for patients who lack such units. This trial was registered at www.clinicaltrials.gov as #NCT01067300.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Leucemia/terapia , Síndromes Mielodisplásicas/terapia , Condicionamento Pré-Transplante/métodos , Doença Aguda , Adolescente , Adulto , Soro Antilinfocitário/administração & dosagem , Criança , Pré-Escolar , Doença Crônica , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Leucemia/mortalidade , Masculino , Síndromes Mielodisplásicas/mortalidade , Taxa de Sobrevida , Irradiação Corporal Total , Adulto Jovem
8.
Front Pediatr ; 3: 79, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26484337

RESUMO

Evans syndrome (ES) is a rare autoimmune disorder whose long-term outcome is not well known. In France, a collaborative pediatric network set up via the National Rare Disease Plan now provides comprehensive clinical data in children with this disease. Patients aged less than 18 years at the initial presentation of autoimmune cytopenia have been prospectively included into a national observational cohort since 2004. The definition of ES was restricted to the simultaneous or sequential association of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP). Cases were deemed secondary if associated with a primitive immunodeficiency or systemic lupus erythematosus. In December 2014, we analyzed the data pertaining to 156 children from 26 centers with ES whose diagnosis was made between 1981 and 2014. Median age (range) at the onset of cytopenia was 5.4 years (0.2-17.2). In 85 sequential cases, the time lapse between the first episodes of AIHA and ITP was 2.4 years (0.1-16.3). The follow-up period as from ES diagnosis was 6.5 years (0.1-28.8). ES was secondary, revealing another underlying disease, in 10% of cases; various associated immune manifestations (mainly lymphoproliferation, other autoimmune diseases, and hypogammaglobulinemia) were observed in 60% of cases; and ES remained primary in 30% of cases. Five-year ITP and AIHA relapse-free survival were 25 and 61%, respectively. Overall, 69% of children required one or more second-line immune treatments, and 15 patients (10%) died at the age of 14.3 years (1.7-28.1). To our knowledge, this is the first consistent long-term clinical description of this rare syndrome. It underscores the high rate of associated immune manifestations and the burden of long-term complications and treatment toxicity. Future challenges include (1) the identification of the underlying genetic defects inducing immune dysregulation and (2) the need to better characterize patient subgroups and second-line treatment strategies.

9.
Pediatr Blood Cancer ; 62(10): 1733-8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25893277

RESUMO

BACKGROUND: Rhabdomyosarcoma (RMS) occasionally occurs in a context of a predisposition syndrome. The most common predisposition syndromes include germline TP53 mutations and constitutive alterations in RAS pathway activation, such as Costello syndrome, Noonan syndrome and neurofibromatosis type 1. We report a national retrospective series of 16 RMS occurring in neurofibromatosis type 1 (NF1) patients during childhood, within a 20-year period. RESULTS: The mean age at diagnosis of the cancer was 2.5 years. All were embryonal subtype. Most tumours developed in the pelvis. One was metastatic. Chemotherapy and radiotherapy were normally scheduled without any specific toxicity. The 5-year event-free survival and overall survival were 67% and 87%, respectively. Long-term sequel related to chemotherapy consisted in two chronic tubulopathies, hence not obviously different from non-NF1 patients. No second cancer was reported so far with a median follow-up of 9.7 years. The genomic analysis performed on six samples revealed the abnormalities commonly observed in sporadic RMS: gain of chromosome 2 (5/6), 8 (6/6) and chromosome 11p loss of heterozygosity (5/6). Interestingly, we identified small deletions in tumour suppressor genes that may synergize with NF1 inactivation. CONCLUSIONS: Patients with neurofibromatosis are prone to develop embryonal-type RMS that require the same treatment as sporadic cases.


Assuntos
Neurofibromatose 1/complicações , Rabdomiossarcoma/complicações , Pré-Escolar , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rabdomiossarcoma/genética , Rabdomiossarcoma/mortalidade
10.
Bull Acad Natl Med ; 197(4-5): 877-86; discussion 886, 2013.
Artigo em Francês | MEDLINE | ID: mdl-25518156

RESUMO

The toxicity of cancer therapies can affect all organs and tissues. Some treatments damage spermatogonial stem cells (SSCs), with a risk of infertility. Storage and reimplantation of frozen testicular tissue is a recent approach tofertilitypreservationfor young boys. However, thawed frozen prepubertal testicular tissue must undergo a maturation process to restore sperm production. This process, currently being studied in animal models, can be achieved by in vivo transplantation of SSCs into seminiferous tubules or by testicular grafting, possibly following in vitro maturation.


Assuntos
Criopreservação , Preservação da Fertilidade/métodos , Infertilidade Masculina/prevenção & controle , Reimplante , Testículo/cirurgia , Adolescente , Animais , Antineoplásicos/efeitos adversos , Criança , Pré-Escolar , Criopreservação/métodos , Humanos , Lactente , Infertilidade Masculina/etiologia , Masculino , Neoplasias/terapia , Radioterapia/efeitos adversos , Túbulos Seminíferos , Espermatogônias , Testículo/efeitos dos fármacos , Testículo/efeitos da radiação , Transplante Autólogo , Transplante Heterotópico
11.
Thromb Res ; 128(3): 261-7, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21507465

RESUMO

BACKGROUND: Complications of bone marrow transplantation (BMT) are usually considered to be related to the secretion of inflammatory cytokines, which generate membrane microparticles rich in procoagulant phospholipids (PPL) from different cellular origins and release of endothelial proteins such as thrombomodulin (TM). The use of soluble TM quantified by ELISA (TM:Ag) as a marker of endothelial injury is complex in children since it is age-dependent. MATERIALS AND METHODS: Using a functional assay which quantifies the activity of sTM activity (TMa), we performed a pilot study to analyze the ratio TMa/TM:Ag in a control group of 25 healthy children, 8 children with autologous and 16 children with allogeneic BMT. In this last group, 8 experienced BMT complications. In addition, we used a functional assay which quantifies PPL. RESULTS: In healthy children the ratio TMa/TM:Ag was independent of age and stable in children with a favorable outcome but significantly (p<0.05) reduced by the use of antithymocyte globulin during the conditioning regimen, and regularly decreased in children with BMT complications. Surprisingly, low plasma PPL levels were associated with a poor outcome. CONCLUSION: The ratio TMa/TM:Ag could constitute a marker of endothelium injury, and its follow-up could be of interest for an early discrimination of children with high risk of complications during allogeneic BMT. The decrease of PPL could be also another marker of a poor evolution and deserves further investigations.


Assuntos
Transplante de Medula Óssea/efeitos adversos , Fosfolipídeos/sangue , Trombomodulina/sangue , Adolescente , Biomarcadores/sangue , Fatores de Coagulação Sanguínea/metabolismo , Plaquetas/metabolismo , Plaquetas/patologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino
12.
Bull Cancer ; 98(2): 209-16, 2011 Feb.
Artigo em Francês | MEDLINE | ID: mdl-21382773

RESUMO

BACKGROUND AND METHODOLOGY: The paediatric rare tumours group from the Société française des cancers de l'enfant makes syntheses and guidelines for diagnosis and treatment for localized paediatric inflammatory myofibroblastic tumours according to international articles. MAIN UPDATING: All ages are concerning. Localizations are ubiquitous, more frequently in the superior and inferior airway. Histology showed a majority of fusiform cells, corresponding to myofibroblastic cells and an inflammatory infiltrate. Inflammatory myofibroblastic tumour diagnosis should only be confirmed in the absence of sarcoma molecular markers. CONCLUSIONS: Distinction between inflammatory myofibroblastic tumour and sarcoma is essential due to the different care. The curative treatment of inflammatory myofibroblastic tumour consists on surgery with before or after corticotherapy. In case of unresectability, chemotherapy may be helpful to avoid mutilating surgery.


Assuntos
Granuloma de Células Plasmáticas/diagnóstico , Granuloma de Células Plasmáticas/terapia , Criança , França , Granuloma de Células Plasmáticas/patologia , Humanos
13.
Biol Blood Marrow Transplant ; 16(3): 430-4, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19883775

RESUMO

Peripheral blood stem cell transplantation (PBSCT) is an alternative to bone marrow transplantation (BMT). Although CD4(+)CD25(+)CD127(lo) regulatory T cells (Tregs) have been shown to play important roles in the control of T cell reactivity, the Treg contents of both graft types have not been analyzed comparatively to date. We report herein that Treg frequencies are significantly reduced in PBSC compared to BM transplants. Furthermore, most Tregs from PBSC transplants are CD62L(lo), a phenotype reported to have poor suppressor activity. Both granulocyte-colony stimulating factor (G-CSF) administration and leukapheresis were found to contribute to the loss of CD62L(+) Tregs. Although higher T cell numbers are infused in PBSCT than in BMT, it is possible that the reduced Treg content of PBSC transplants may represent 1 factor contributing to the higher risk of GVHD reported after PBSCT.


Assuntos
Transplante de Medula Óssea , Transplante de Células-Tronco de Sangue Periférico , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/transplante , Apoptose/imunologia , Medula Óssea/efeitos dos fármacos , Fatores de Transcrição Forkhead/análise , Doença Enxerto-Hospedeiro/imunologia , Fator Estimulador de Colônias de Granulócitos/farmacologia , Humanos , Imunofenotipagem , Subunidade alfa de Receptor de Interleucina-7/análise , Selectina L/análise , Leucaférese , Antígenos Comuns de Leucócito/análise , Contagem de Linfócitos , Fatores de Risco , Subpopulações de Linfócitos T/química , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/transplante , Linfócitos T Reguladores/química , Linfócitos T Reguladores/imunologia , Doadores de Tecidos
14.
Clin Immunol ; 127(1): 14-25, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18191619

RESUMO

Transitional B cells have been recently identified in human peripheral blood. However, their precise role in human B cell differentiation has not been established. Therefore, besides characterizing them further in the blood of healthy adults and children and cord blood, we used the immune reconstitution after hematopoietic stem cell transplantation (HSCT) model to define their role in human B cell development. Human transitional B cells are reliably identified as CD19(+) CD24(high) CD38(high) lymphocytes and represent approximately 4% of B cells in healthy adult peripheral blood. In contrast, they are abundant in cord blood (near 50% of B cells) and their percentage progressively decreases during infancy. Similarly, after HSCT, all B cells first appearing in peripheral blood are transitional B cells; afterwards, the transitional B cell percentage progressively decreases while the mature naïve B cell proportion rises. Our results now formally demonstrate that transitional B cells are necessary developmental intermediates for human mature B cell generation.


Assuntos
Subpopulações de Linfócitos B/citologia , Linfócitos B/citologia , Diferenciação Celular/imunologia , Transplante de Células-Tronco Hematopoéticas , Células Precursoras de Linfócitos B/citologia , Adulto , Antígenos CD/biossíntese , Subpopulações de Linfócitos B/imunologia , Linfócitos B/imunologia , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Células Precursoras de Linfócitos B/imunologia
15.
Haematologica ; 92(5): 589-96, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17488681

RESUMO

BACKGROUND AND OBJECTIVES: Severe acquired aplastic anemia (SAA) is a potentially fatal bone marrow failure syndrome occurring mainly in children and young adults. Immunosuppressive regimens and hematopoietic stem cell transplantation (HSCT) are the only two available curative treatments. Patients who lack an HLA-identical sibling donor may receive HSCT from an unrelated donor, a strategy historically associated with high mortality rates. Thus, for patients refractory to immunosuppressive regimens, the decision to transplant stem cells from unrelated donors is weighed against supportive care and often represents a dilemma for physicians. We aimed to determine whether outcome after unrelated HSCT has improved in recent years and, if so, to determine the factors responsible for the improvement. DESIGN AND METHODS: We analyzed the outcome of 89 patients (median age 17 years, range 0-52) with acquired SAA undergoing HSCT from an unrelated donor between 1989 and 2004. Cases were consecutively reported to the French Registry (SFGM-TC) by 25 centers. RESULTS: Patients transplanted during two successive time-periods (1989-1998 and 1999-2004) had different 5-year survival probabilities (+/-95% confidence interval): 29%+/-7% and 50%+/-7%, respectively (p<0.01). The main difference between the two cohorts concerned HLA matching between donors and recipients at the allelic level for the ten HLA-A, -B, -C, -DRB1 and -DQB1 antigens, which was more frequent in 1999-2004 than in the former period (p=0.0004). In multivariate analysis, the only two factors affecting survival were HLA allelic matching (p<0.01) and younger age of recipient (17 pounds sterling years, p<0.0001). Survival reached 78%+/-11% at 5 years for the younger, fully HLA-matched patients. INTERPRETATION AND CONCLUSIONS: Survival after unrelated HSCT for SAA has improved significantly over the past 15 years, mainly due to better HLA matching. Results for young patients who are fully HLA-matched at the allelic level with their donor are comparable to those observed after HSCT from a related donor.


Assuntos
Anemia Aplástica/cirurgia , Antígenos HLA/imunologia , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Teste de Histocompatibilidade/métodos , Transplante Homólogo/estatística & dados numéricos , Adolescente , Adulto , Anemia Aplástica/tratamento farmacológico , Anemia Aplástica/etiologia , Anemia Aplástica/mortalidade , Soro Antilinfocitário/administração & dosagem , Causas de Morte , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Estudos de Coortes , Terapia Combinada , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Antígenos HLA/análise , Antígenos HLA/genética , Hemoglobinúria Paroxística/complicações , Hepatite/complicações , Humanos , Imunossupressores/uso terapêutico , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Doadores Vivos , Depleção Linfocítica , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Reoperação , Estudos Retrospectivos , Estatísticas não Paramétricas , Análise de Sobrevida , Taxa de Sobrevida , Linfócitos T , Fatores de Tempo , Condicionamento Pré-Transplante/métodos , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados
16.
Transplantation ; 80(6): 782-8, 2005 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-16210965

RESUMO

BACKGROUND: The use of monoclonal antibodies against interleukin-2 receptor (IL-2R)-alpha chains could be an effective treatment of acute graft-versus-host disease (GvHD). Experimental model and clinical studies have reported various results. METHODS: Inolimomab is a murine anti-IL-2R. Eighty-five patients were evaluated retrospectively for the safety and efficacy of inolimomab given for the treatment of steroid-resistant acute GvHD (aGvHD) following allogeneic hematopoietic stem cell transplantation (HSCT). Diseases were immune deficiency, hematological malignancies, or solid tumors. Seventy-six percent of the patients received a myeloablative regimen. The source of HSCT was bone marrow for 45 patients, peripheral blood for 36 patients, and cord blood for 4 patients. Donors were 49 siblings and 36 unrelated. Acute GvHD was diagnosed within a median of 28 days after transplantation (grade II, 26 patients; grade III, 26 patients; grade IV, 33 patients). Inolimomab was administered in the event of steroid-resistant aGvHD with a median dose of 0.468 mg per kg (median period of treatment: 18 days). RESULTS: Twenty-five complete responses and 29 partial responses (total response rate: 63%) were observed with no side effects. There was no correlation between aGvHD grading and quality of response. Better responses were observed in cutaneous aGvHD. The overall survival probability was 26% (median follow-up: 20 months). Fifty-seven percent of patients died of toxicity related mortality, mostly aGvHD. Response to inolimomab seemed sustained (11% relapse in responders). CONCLUSION: Inolimomab is well-tolerated and effective for severe steroid-resistant aGvHD. The optimum regimen remains to be defined.


Assuntos
Corticosteroides/farmacologia , Anticorpos Monoclonais/uso terapêutico , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas , Imunoterapia , Receptores de Interleucina-2/imunologia , Doença Aguda , Adolescente , Corticosteroides/farmacocinética , Corticosteroides/uso terapêutico , Adulto , Anticorpos Monoclonais/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Homólogo
17.
Clin Infect Dis ; 34(9): 1170-8, 2002 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-11941542

RESUMO

This study assessed the epidemiologic characteristics of acute viral gastroenteritis in hospitalized children. A stool sample obtained from each child was analyzed for the presence of astrovirus, calicivirus, rotavirus, adenovirus, enterovirus, and digestive bacteria. Of the 438 stool samples obtained, 138 tested positive for > or =1 pathogen during the winters of 1997-1998 and 1998-1999 (P<.001). Virologic tests revealed rotavirus in 17.3% of samples, calicivirus in 7.3%, astrovirus in 6.8%, adenovirus in 0.7%, and > or =1 virus in 5.4%. Median age was higher for patients with rotavirus gastroenteritis than it was for those with astrovirus or calicivirus gastroenteritis (P=.014). Mean duration of hospitalization was statistically significantly lower for children with rotavirus gastroenteritis (P=.022), despite the more-frequent dehydration observed among children with rotavirus versus those with astrovirus or calicivirus gastroenteritis (P=.007). In contrast, enteral rehydration was more rapidly achieved in patients with gastroenteritis due to rotavirus.


Assuntos
Gastroenterite/epidemiologia , Infecções por Rotavirus/epidemiologia , Doença Aguda , Pré-Escolar , Desidratação/etiologia , França/epidemiologia , Gastroenterite/fisiopatologia , Gastroenterite/virologia , Hospitalização , Humanos , Lactente , Recém-Nascido , Rotavirus , Infecções por Rotavirus/fisiopatologia
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