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1.
J Clin Immunol ; 39(2): 195-199, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30868346

RESUMO

X-linked chronic granulomatous disease (XL-CGD), a rare primary immunodeficiency due to a defect in the gp91phox NADPH oxidase subunit, results in recurrent, severe infection, inflammation, and autoimmunity. Patients have an absent, or significantly reduced, neutrophil oxidative burst. Due to lyonization, XL-CGD carriers have a dual population of functional and non-functional phagocytes and experience a range of symptoms including increased risk of autoimmunity, fatigue, and infection. Patients with CGD have poorer quality of life (QoL) than normal controls. We evaluated QoL and psychological health in UK XL-CGD carriers. Recruited participants completed the Medical Outcomes Study Short Form 36 version 2 (SF-36 V2), providing an overall score for mental and physical health. Psychological health was assessed using the Hospital Anxiety and Depression Scale (HADS) questionnaire. Seventy-five XL-CGD carriers were recruited from 62 families, median age 43 years (range 3-77). Fifty-six were mothers, 6 grandmothers, and 13 siblings. Sixty-two completed the SF36v2 and had reduced QoL scores compared with adult CGD patients and a UK age-matched female control cohort, indicating a reduced QoL. Sixty-one completed a HADS questionnaire. Over 40% experienced moderate or greater levels of anxiety with only one third being classified as normal. Higher anxiety scores significantly correlated with higher depression scores, lower self-esteem, presence of joint or bowel symptoms, and higher levels of fatigue (p < 0.05). This is the first study to evaluate QoL of XL-CGD carriers, and demonstrates high rates of anxiety and significantly reduced QoL scores. XL-CGD carriers should be considered as potential patients and pro-actively assessed and managed.

2.
J Clin Immunol ; 2018 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-29744786

RESUMO

The original version of the article, "Raised Serum IL-8 Levels Are Associated with Excessive Fatigue in Female Carriers of X-Linked Chronic Granulomatous Disease in the UK" incorrectly listed the name of the fourth author as Fai W. Ng. The correct spelling of the author's name is WF Ng.

5.
Am J Hum Genet ; 100(2): 281-296, 2017 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-28132690

RESUMO

EXTL3 regulates the biosynthesis of heparan sulfate (HS), important for both skeletal development and hematopoiesis, through the formation of HS proteoglycans (HSPGs). By whole-exome sequencing, we identified homozygous missense mutations c.1382C>T, c.1537C>T, c.1970A>G, and c.2008T>G in EXTL3 in nine affected individuals from five unrelated families. Notably, we found the identical homozygous missense mutation c.1382C>T (p.Pro461Leu) in four affected individuals from two unrelated families. Affected individuals presented with variable skeletal abnormalities and neurodevelopmental defects. Severe combined immunodeficiency (SCID) with a complete absence of T cells was observed in three families. EXTL3 was most abundant in hematopoietic stem cells and early progenitor T cells, which is in line with a SCID phenotype at the level of early T cell development in the thymus. To provide further support for the hypothesis that mutations in EXTL3 cause a neuro-immuno-skeletal dysplasia syndrome, and to gain insight into the pathogenesis of the disorder, we analyzed the localization of EXTL3 in fibroblasts derived from affected individuals and determined glycosaminoglycan concentrations in these cells as well as in urine and blood. We observed abnormal glycosaminoglycan concentrations and increased concentrations of the non-sulfated chondroitin disaccharide D0a0 and the disaccharide D0a4 in serum and urine of all analyzed affected individuals. In summary, we show that biallelic mutations in EXTL3 disturb glycosaminoglycan synthesis and thus lead to a recognizable syndrome characterized by variable expression of skeletal, neurological, and immunological abnormalities.


Assuntos
Anormalidades Musculoesqueléticas/genética , N-Acetilglucosaminiltransferases/genética , Osteocondrodisplasias/genética , Alelos , Linhagem Celular , Linhagem Celular Tumoral , Condroitina/sangue , Condroitina/urina , Variações do Número de Cópias de DNA , Estudo de Associação Genômica Ampla , Glicosaminoglicanos/metabolismo , Humanos , Anormalidades Musculoesqueléticas/diagnóstico , Mutação de Sentido Incorreto , Osteocondrodisplasias/diagnóstico , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/genética
6.
Br J Haematol ; 174(6): 942-51, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27291859

RESUMO

Standard quality assurance (QA) of cryopreserved peripheral blood stem cells (PBSC) uses post-thaw viable CD34(+) cell counts. In 2013, concerns arose at Great Ormond Street Hospital (GOSH) about 8 patients with delayed engraftment following myeloablative chemotherapy with cryopreserved cell rescue, despite adequate post-thaw viable cell counts in all cases. Root cause analysis was undertaken; investigations suggested the freeze process itself was a contributing factor to suboptimal engraftment. Experiments were undertaken in which a single PBSC product was divided into three and cryopreserved in parallel using a control-rate freezer (CRF) or passive freezing method (-80°C freezer) at GOSH, or the same passive freezing at another laboratory. Viable CD34(+) counts were equivalent and adequate in each. Granulocyte-monocyte colony-forming unit assays demonstrated colonies from the products cryopreserved using passive freezing (both laboratories), but no colonies from products cryopreserved using the CRF. The CRF was shown to be operating within manufacturer's specifications with freeze-profile within acceptable limits. This experience has important implications for quality assurance for all transplant programmes, particularly those using cryopreserved products. The failure of post-thaw viable CD34(+) counts, the most widely used routine QA test available, to ensure PBSC function is of great concern and should prompt reassessment of protocols and QA procedures.


Assuntos
Criopreservação , Células-Tronco de Sangue Periférico/citologia , Células-Tronco de Sangue Periférico/metabolismo , Antígenos CD34/metabolismo , Biomarcadores , Sobrevivência Celular , Ensaio de Unidades Formadoras de Colônias , Criopreservação/métodos , Sobrevivência de Enxerto , Humanos , Contagem de Leucócitos , Transplante de Células-Tronco de Sangue Periférico/métodos , Transplante de Células-Tronco de Sangue Periférico/normas , Garantia da Qualidade dos Cuidados de Saúde , Fatores de Tempo
7.
Brain ; 138(Pt 10): 2834-46, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26122121

RESUMO

Defects of mitochondrial dynamics are emerging causes of neurological disease. In two children presenting with severe neurological deterioration following viral infection we identified a novel homozygous STAT2 mutation, c.1836 C>A (p.Cys612Ter), using whole exome sequencing. In muscle and fibroblasts from these patients, and a third unrelated STAT2-deficient patient, we observed extremely elongated mitochondria. Western blot analysis revealed absence of the STAT2 protein and that the mitochondrial fission protein DRP1 (encoded by DNM1L) is inactive, as shown by its phosphorylation state. All three patients harboured decreased levels of DRP1 phosphorylated at serine residue 616 (P-DRP1(S616)), a post-translational modification known to activate DRP1, and increased levels of DRP1 phosphorylated at serine 637 (P-DRP1(S637)), associated with the inactive state of the DRP1 GTPase. Knockdown of STAT2 in SHSY5Y cells recapitulated the fission defect, with elongated mitochondria and decreased P-DRP1(S616) levels. Furthermore the mitochondrial fission defect in patient fibroblasts was rescued following lentiviral transduction with wild-type STAT2 in all three patients, with normalization of mitochondrial length and increased P-DRP1(S616) levels. Taken together, these findings implicate STAT2 as a novel regulator of DRP1 phosphorylation at serine 616, and thus of mitochondrial fission, and suggest that there are interactions between immunity and mitochondria. This is the first study to link the innate immune system to mitochondrial dynamics and morphology. We hypothesize that variability in JAK-STAT signalling may contribute to the phenotypic heterogeneity of mitochondrial disease, and may explain why some patients with underlying mitochondrial disease decompensate after seemingly trivial viral infections. Modulating JAK-STAT activity may represent a novel therapeutic avenue for mitochondrial diseases, which remain largely untreatable. This may also be relevant for more common neurodegenerative diseases, including Alzheimer's, Huntington's and Parkinson's diseases, in which abnormalities of mitochondrial morphology have been implicated in disease pathogenesis.


Assuntos
Doenças Mitocondriais/genética , Doenças Mitocondriais/metabolismo , Dinâmica Mitocondrial/fisiologia , Fator de Transcrição STAT2/deficiência , Transdução de Sinais/genética , Apoptose/genética , Pré-Escolar , Eletroencefalografia , Saúde da Família , Feminino , Citometria de Fluxo , GTP Fosfo-Hidrolases/genética , GTP Fosfo-Hidrolases/metabolismo , Células HEK293 , Humanos , Lactente , Masculino , Microscopia Eletrônica , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Músculo Esquelético/patologia , Músculo Esquelético/ultraestrutura , Neuroblastoma/patologia , Fosforilação , Processamento de Proteína Pós-Traducional , RNA Nuclear Pequeno/farmacologia , Fator de Transcrição STAT2/genética , Transfecção
8.
Clin Immunol ; 149(3): 464-74, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24230999

RESUMO

Defective V(D)J recombination and DNA double-strand break (DSB) repair severely impair the development of T-lymphocytes and B-lymphocytes. Most patients manifest a severe combined immunodeficiency during infancy. We report 2 siblings with combined immunodeficiency (CID) and immunodysregulation caused by compound heterozygous Artemis mutations, including an exon 1-3 deletion generating a null allele, and a missense change (p.T71P). Skin fibroblasts demonstrated normal DSB repair by gamma-H2AX analysis, supporting the predicted hypomorphic nature of the p.T71P allele. In addition to these two patients, 12 patients with Artemis-deficient CID were previously reported. All had significant morbidities including recurrent infections, autoimmunity, EBV-associated lymphoma, and carcinoma despite having hypomorphic mutants with residual Artemis expression, V(D)J recombination or DSB repair capacity. Nine patients underwent stem cell transplant and six survived, while four patients who did not receive transplant died. The progressive nature of immunodeficiency and genomic instability accounts for poor survival, and early HSCT should be considered.


Assuntos
Estudos de Associação Genética , Mutação , Proteínas Nucleares/genética , Imunodeficiência Combinada Severa/genética , Adulto , Sequência de Aminoácidos , Pré-Escolar , Endonucleases , Feminino , Heterogeneidade Genética , Instabilidade Genômica , Heterozigoto , Humanos , Lactente , Dados de Sequência Molecular , Proteínas Nucleares/imunologia , Imunodeficiência Combinada Severa/imunologia , Imunodeficiência Combinada Severa/patologia , Irmãos , Recombinação V(D)J/imunologia
9.
J Allergy Clin Immunol ; 132(5): 1150-5, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23870668

RESUMO

BACKGROUND: Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by serious infections and inflammation. It can be managed conservatively with prophylactic antimicrobial agents or curatively with hematopoietic stem cell transplantation (HSCT). In the United Kingdom and Ireland there are cohorts of children managed both conservatively and curatively. OBJECTIVES: This study aimed to compare clinical outcomes (mortality and morbidity) in children managed conservatively and curatively. METHODS: Children were identified from specialist centers and advertising through special interest groups. Clinical data were collected from medical records regarding infections, inflammatory complications and growth, other admissions, and curative treatment. Comparisons were made for patients not undergoing HSCT and patients after HSCT. RESULTS: Seventy-three living children were identified, 59 (80%) of whom were recruited. Five deceased children were also identified. Clinical information was available for 62 children (4 deceased). Thirty (48%) children had undergone HSCT. Children who did not undergo transplantation had 0.71 episodes of infection/admission/surgery per CGD life year (95% CI, 0.69-0.75 events per year). Post-HSCT children had 0.15 episodes of infection/admission/surgery per transplant year (95% CI, 0.09-0.21 events per year). The mean z score for height and body mass index (BMI) for age was significantly better in post-HSCT children. Survival in the non-HSCT group was 90% at age 15 years. Survival in the post-HSCT group was 90%. CONCLUSIONS: Children with CGD not undergoing transplantation have more serious infections, episodes of surgery, and admissions compared with post-HSCT children. Children undergoing transplantation have better height for age. Survival is good at the end of the pediatric age range and also after HSCT.


Assuntos
Doença Granulomatosa Crônica/epidemiologia , Adolescente , Criança , Pré-Escolar , Feminino , Doença Granulomatosa Crônica/terapia , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Recém-Nascido , Infecção/etiologia , Irlanda , Masculino , Morbidade , Mortalidade , Resultado do Tratamento , Reino Unido
10.
Neuropediatrics ; 44(4): 230-2, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23397467

RESUMO

Chronic granulomatous disease (CGD) is a primary immunodeficiency managed conservatively or with hematopoietic stem cell transplant. Studies have shown people with CGD and those transplanted for primary immunodeficiencies have lower than average cognitive ability. In this study, IQ in children with CGD and those transplanted for it was within the normal range.


Assuntos
Transtornos Cognitivos/etiologia , Transtornos Cognitivos/cirurgia , Doença Granulomatosa Crônica/complicações , Doença Granulomatosa Crônica/cirurgia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Irlanda , Masculino , Testes Neuropsicológicos , Resultado do Tratamento , Reino Unido
11.
J Clin Immunol ; 33(1): 8-13, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23011479

RESUMO

PURPOSE: Chronic Granulomatous Disease (CGD) is a rare primary immunodeficiency that predisposes to life-threatening infections and inflammation. Haematopoietic stem cell transplant (HSCT) can cure CGD. Chronic illness reduces quality of life. Children with haematological malignancies report improved quality of life post-HSCT. There are no data for children with CGD. This study evaluated quality of life and emotional well-being in CGD children treated conventionally or transplanted. METHODS: Parents and children completed the Pediatric Quality of Life Inventory v4.0 (PedsQL) and Strengths and Difficulties Questionnaires (SDQ). Mean scores were compared with published UK norms. Comparisons were made for those that had or had not undergone HSCT. RESULTS: Forty-seven parents completed PedsQL (children aged 3-15). Twenty-one were post-HSCT. Forty-two completed SDQ (children aged 3-15). Nineteen post-HSCT. Median age for non-HSCT group 9 years. Median age for post-HSCT group 10 years. The HSCT group were median 3 years post-HSCT (range 1-9 years). HSCT survival was 90 %-two died without completing questionnaires Parent and self-reported quality of life for non-transplanted children was significantly lower than healthy children. Parents reported increased emotional difficulties compared to published norms. PedsQL and SDQ scores for transplanted children were not significantly different from healthy norms. CONCLUSIONS: This study demonstrates the quality of life is reduced in CGD. Transplanted patients have quality of life comparable to levels reported in healthy children. This data will help inform families and clinicians when deciding about treatment and may have relevance for other immunodeficiencies treated with transplant.


Assuntos
Emoções , Doença Granulomatosa Crônica/imunologia , Doença Granulomatosa Crônica/terapia , Nível de Saúde , Transplante de Células-Tronco Hematopoéticas , Qualidade de Vida , Adolescente , Criança , Pré-Escolar , Feminino , Doença Granulomatosa Crônica/psicologia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Lactente , Masculino , Qualidade de Vida/psicologia , Inquéritos e Questionários
12.
Pediatr Crit Care Med ; 13(5): 535-41, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22760424

RESUMO

OBJECTIVE: To evaluate whether intravenous immunoglobulin was linked to a reduction in sepsis in patients with prolonged chylothoraces postpediatric cardiothoracic surgery. DESIGN: Retrospective observational cohort study. SETTING: Tertiary pediatric cardiac surgical center. PATIENTS: Children with chylothoraces postcardiothoracic surgery from 1998 to 2006 divided into two groups: with and without intravenous immunoglobulin supplementation. INTERVENTION: Intravenous immunoglobulin supplementation. MEASUREMENTS AND MAIN RESULTS: Thirty-seven with chylothoraces (median duration 14 days; interquartile range, 10-32 and median maximum chyle drainage 1.9 mL/kg/hr; interquartile range, 1-3) were included, and 16 (43%) received intravenous immunoglobulin. The degree of lymphopenia was worse with longer duration of chylothorax (p = .005). There was a trend toward immunoglobulin depletion-IgG (p = .07) and IgM (p = .07) with higher volume chyle loss. Twenty-two of 37 (59%) developed bloodstream infection and 24 of 37 (65%) developed sepsis related to other organ systems. The rate of bloodstream infection and of sepsis in other organ systems was high at 25 (95% confidence interval 17-39) and 23 (95% confidence interval 15-34) episodes per 1,000 intensive care unit days, respectively. Intravenous immunoglobulin was not related to the bloodstream infection rate: adjusted hazard ratio 0.88 (95% confidence interval 0.20-3.94; p = .87) or rate of sepsis in other organ systems: hazard ratio 2.31 (95% confidence interval 0.21-24.29; p = .49) or the proportion surviving to hospital discharge (p = .37). CONCLUSION: Patients with prolonged, large-volume chyle loss had greater secondary immunodeficiency. Although the sample size was small and therefore able to detect only a large treatment effect from intravenous immunoglobulin, infectious outcomes were equal between the two groups.


Assuntos
Quilotórax/imunologia , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Complicações Pós-Operatórias/imunologia , Sepse/prevenção & controle , Análise Atuarial , Quilotórax/complicações , Drenagem , Cardiopatias Congênitas/cirurgia , Humanos , Deficiência de IgG/etiologia , Imunoglobulina M/deficiência , Recém-Nascido , Modelos Logísticos , Linfopenia/etiologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Sepse/etiologia , Índice de Gravidade de Doença
15.
Pediatrics ; 121(4): e998-1002, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18316354

RESUMO

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome is a rare X-linked disorder that usually presents in early childhood with immune enteropathy, diabetes mellitus, and other autoimmune complications. The disease is caused by mutations in the forkhead box P3 gene, a transcription factor that is essential for the development and function of regulatory T cells. This population of cells plays an essential role in controlling immune responses and preventing autoimmunity. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome is often initially treated with immunosuppressive drugs, but only allogeneic hematopoietic stem cell transplantation has offered the possibility of cure. We recently performed an unrelated donor transplant in a child with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome by using a reduced-intensity conditioning regimen. This transplant provided a rare opportunity to gain valuable insight into the regeneration of the immune system after transplantation. Clinical recovery was associated with the emergence of regulatory T cell populations, the majority of which expressed memory phenotype markers and raised important questions about the origin and longevity of the FOXP3(+) regulatory T cell pool.


Assuntos
Fatores de Transcrição Forkhead/metabolismo , Doenças Genéticas Ligadas ao Cromossomo X/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Poliendocrinopatias Autoimunes/diagnóstico , Poliendocrinopatias Autoimunes/terapia , Linfócitos T Reguladores/imunologia , Seguimentos , Fatores de Transcrição Forkhead/genética , Expressão Gênica , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Sobrevivência de Enxerto , Humanos , Lactente , Masculino , Poliendocrinopatias Autoimunes/genética , Reação em Cadeia da Polimerase , Enteropatias Perdedoras de Proteínas/genética , Enteropatias Perdedoras de Proteínas/imunologia , Enteropatias Perdedoras de Proteínas/terapia , Medição de Risco , Síndrome , Linfócitos T Reguladores/metabolismo , Transplante Homólogo , Resultado do Tratamento
16.
Eur J Med Genet ; 50(5): 338-45, 2007 Sep-Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17684005

RESUMO

Immune deficiency can be part of CHARGE syndrome but often receives only limited attention. We present two patients with CHARGE syndrome confirmed CHD7 mutations who had severe T-cell deficiency, and review 15 CHARGE patients from the literature with immunological problems. Most of them had severe T-cell deficiency, although the spectrum also included mild T-cell deficiency and isolated humoral immune deficiency. We conclude that immunodeficiency can form an important symptom in CHARGE syndrome although the frequency and exact nature are still insufficiently known. We propose to evaluate immune functions in all CHARGE syndrome patients, to estimate the frequency and nature of the accompanying immunodeficiency, and to obtain better data regarding prognosis and management.


Assuntos
Anormalidades Múltiplas/imunologia , Anormalidades Múltiplas/genética , Atresia das Cóanas/genética , Atresia das Cóanas/imunologia , Códon sem Sentido , Coloboma/genética , Coloboma/imunologia , DNA Helicases/genética , Proteínas de Ligação a DNA/genética , Transtornos do Crescimento/genética , Transtornos do Crescimento/imunologia , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/imunologia , Humanos , Recém-Nascido , Masculino , Fenótipo , Síndrome , Linfócitos T/imunologia
17.
J Heart Lung Transplant ; 24(9): 1284-8, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16143246

RESUMO

BACKGROUND: More children are coming to heart transplantation on extracorporeal membrane oxygenation (ECMO), or inotropic support and/or with renal impairment. The use of basiliximab, a chimeric monoclonal antibody against CD25 (interleukin 2 receptor alfa) has not been previously reported in critically ill pediatric heart transplant recipients. Basiliximab has potential advantages in the treatment of patients with renal impairment. METHODS: Basiliximab was provided to 29 patients (median age 7.8 years; range 0.4-16 years) on ECMO, with renal impairment or receiving intravenous inotropes at transplantation. Children normally received 2 doses on Day 0 and Day 4 after transplantation. Calcineurin inhibitor was provided in low dose or withheld altogether in patients with renal impairment. Flow cytometry was used to monitor CD25. RESULTS: At transplantation, 11 patients were prescribed cyclosporine; the remaining 18 received tacrolimus. All but 4 patients had subtherapeutic levels of calcineurin inhibitor in the first postoperative week. Excluding these 4, there were 19 patients who had more than 4 consecutive doses of calcineurin inhibitor canceled in the first week (median 8 doses; range 3-40 doses). A total of 71 surveillance biopsies were performed, and 4 episodes of severe acute rejection occurred in the first 6 months. In all but one child, the glomerular filtration rate had returned to, or improved on baseline measurement by 1 month after transplantation. Infections rates were low and acceptable. CD25 was undetectable at first assessment, and in all but 1 patient (on ECMO) for at least 2 to 3 weeks thereafter. There were no adverse effects. CONCLUSIONS: Basiliximab was well tolerated in this group of very ill children. In children with pre- or postoperative renal dysfunction, where doses of calcineurin inhibitor were low or canceled, basiliximab was associated with a low incidence of rejection. Posttransplant ECMO may reduce the efficacy of basiliximab. These preliminary results are encouraging and now need confirmation in a large, randomized trial.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Transplante de Coração , Imunossupressores/uso terapêutico , Rim/efeitos dos fármacos , Proteínas Recombinantes de Fusão/uso terapêutico , Proteínas Adaptadoras de Transdução de Sinal , Adolescente , Basiliximab , Calcineurina/sangue , Criança , Pré-Escolar , Ciclosporina/uso terapêutico , Oxigenação por Membrana Extracorpórea , Feminino , Rejeição de Enxerto/prevenção & controle , Transplante de Coração/imunologia , Humanos , Lactente , Rim/fisiopatologia , Nefropatias/complicações , Masculino , Fosfoproteínas/sangue , Receptores de Interleucina-2/antagonistas & inibidores , Receptores de Interleucina-2/sangue , Tacrolimo/uso terapêutico
18.
Blood ; 105(2): 879-85, 2005 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-15367433

RESUMO

The optimal approach to stem cell transplantation in children with immunodeficiency who lack a matched family donor is controversial. Unrelated donor stem cell transplantation gives equivalent outcome to mismatched family donor stem cell transplantation in severe combined immunodeficiency, whereas unrelated donors may be preferable in non-severe combined immunodeficiency children. However, unrelated donor stem cell transplantation with conventional conditioning regimens has been associated with significant treatment-related toxicity, particularly in non-severe combined immunodeficiency patients with preexisting organ dysfunction. We report the outcome of a series of 33 consecutive unrelated donor transplantations performed at our center in children with primary immunodeficiency using a reduced-intensity conditioning regimen between 1998 and 2001. We have compared these outcomes with a retrospective control cohort of 19 patients who underwent transplantation with myeloablative conditioning between 1994 and 1998. All children in both groups had primary engraftment. There was no statistical difference in the speed of immune reconstitution or incidence of graft-versus-host disease between the 2 groups. Overall survival was significantly better in the reduced-intensity conditioning group: 31 (94%) of 33 patients survived, compared with 10 (53%) of 19 in the myeloablative conditioning group (P = .014). We conclude that the reduced-intensity conditioning regimen results in improved survival and reduced transplantation-related mortality compared with myeloablative conditioning in high-risk patients undergoing unrelated donor transplantation.


Assuntos
Transplante de Medula Óssea/mortalidade , Imunodeficiência Combinada Severa/mortalidade , Imunodeficiência Combinada Severa/terapia , Condicionamento Pré-Transplante/métodos , Adolescente , Criança , Pré-Escolar , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Incidência , Lactente , Neutrófilos/citologia , Contagem de Plaquetas , Recuperação de Função Fisiológica/imunologia , Análise de Sobrevida , Doadores de Tecidos , Quimeras de Transplante , Viroses/mortalidade
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