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2.
Nat Rev Drug Discov ; 18(6): 447-462, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30858502

RESUMO

Pioneering gene therapy trials have shown that the genetic engineering of haematopoietic stem and progenitor cells can be an alternative to allogeneic transplantation in the treatment of primary immunodeficiencies. Early trials also highlighted the risk of insertional mutagenesis and oncogene transactivation associated with the first generation of gammaretroviral vectors. These events prompted the development of safer, self-inactivating lentiviral or gammaretroviral vectors. These lentiviral vectors have been successfully used to treat over 200 patients with 10 different haematological disorders (including primary immunodeficiencies, haemoglobinopathies and metabolic disorders) and for the generation of chimeric antigen receptor-T cells for cancer therapy. However, several challenges, such as effective reconstitution during inflammation, remain if gene therapy is to be extended to more complex diseases in which haematopoietic stem and progenitor cells can be altered by the disease environment. We discuss the progress made and future challenges for gene therapy and contrast gene therapy with gene-editing strategies.


Assuntos
Anemia Falciforme/terapia , Terapia Genética/métodos , Vetores Genéticos/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/citologia , Imunodeficiência Combinada Severa/terapia , Talassemia beta/terapia , Anemia Falciforme/genética , Animais , Engenharia Genética , Humanos , Imunodeficiência Combinada Severa/genética , Talassemia beta/genética
3.
N C Med J ; 80(1): 55-56, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30622209
4.
Immunogenetics ; 71(4): 299-305, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30610243

RESUMO

Deficiency of adenosine deaminase 2 (DADA2) is an autoinflammatory disease caused by autosomal recessive mutations in Cat Eye Syndrome Chromosome Region 1 (CECR1) gene. In this report, we aimed to describe the clinical manifestations, immunological features, genotype, and treatments of one Chinese patient with novel CECR1 gene mutations. This patient initially presented with recurrent fever and rashes from the age of 3 months, but no pathogen was found. She then developed dry gangrene of the fingers at 5 months of age. Laboratory examinations revealed elevated levels of C-reactive protein and thrombocytes. The expression of interleukin-6 (IL-6) and IL-8 were both elevated. Sequencing results revealed that she had compound heterozygous mutations in CECR1 gene (c.1211T>C, p.Phe404Ser and c.1114 G>A, p.Val372Met). Subsequently, treatment with anti-IL-6 (tocilizumab) was started. However, she developed blurred vision in the right eye with occlusion of the central retinal artery, accompanied by unsteady gait. Magnetic resonance imaging (MRI) showed infarction of the right thalamus. Finally, she underwent hematopoietic stem cell transplantation (HSCT) and is currently in remission. Our findings suggest that HSCT could cure this disease.


Assuntos
Adenosina Desaminase/deficiência , Agamaglobulinemia/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Doenças Hereditárias Autoinflamatórias/terapia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Mutação , Imunodeficiência Combinada Severa/terapia , Adenosina Desaminase/genética , Agamaglobulinemia/diagnóstico por imagem , Agamaglobulinemia/genética , Grupo com Ancestrais do Continente Asiático , Sequência de Bases , China , Feminino , Doenças Hereditárias Autoinflamatórias/diagnóstico por imagem , Doenças Hereditárias Autoinflamatórias/genética , Humanos , Lactente , Imagem por Ressonância Magnética , Indução de Remissão , Análise de Sequência de DNA , Imunodeficiência Combinada Severa/diagnóstico por imagem , Imunodeficiência Combinada Severa/genética
6.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 48(4): 351-357, 2019 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-31901036

RESUMO

Severe combined immunodeficiency disease (SCID) is a group of rare congenital diseases characterized by severe deficiencies in T lymphocyte counts and/or function. The recurrent, persistent and severe infections are its clinical manifestations. Neonatal screening and immune system reconstruction would improve the prognosis of SCID children. Newborn screening programs based on T-cell receptor excision circles (TRECs) quantitative detection have been carried out in clinical practice, however, the methods still have some limitations. Other new methods such as mass spectrometry and T lymphocyte-specific biomarker assays are still under investigation. Hematopoietic stem cell transplantation and gene therapy are the two main methods for reconstructing immune function in SCID children. Through improving the success rate of transplantation and the long-term safety and stability of viral vectors, some achievements have been made by many centers already. However, large-scale prospective studies are needed for evaluation of the long-term efficacy. In this article, the recent progress in newborn screening and immune reconstitution of SCID is reviewed.


Assuntos
Reconstituição Imune , Triagem Neonatal , Imunodeficiência Combinada Severa , Humanos , Recém-Nascido , Triagem Neonatal/tendências , Estudos Prospectivos , Imunodeficiência Combinada Severa/terapia , Linfócitos T
7.
J Pediatric Infect Dis Soc ; 7(suppl_2): S79-S82, 2018 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-30590619

RESUMO

Hematopoietic stem cell transplantation (HSCT) has been the standard of care for infants with severe combined immunodeficiency (SCID) for several decades due to the dismal prognosis early in life without immune reconstitution. In recent years, as HSCT conditioning regimens and supportive care have greatly improved, HSCT is gaining in acceptance for more non-SCID primary immunodeficiencies (PIDs) and outside the early childhood period. In addition, potential donor options for non-SCID PIDs are expanding with increasing success for haploidentical donor transplants. In this brief report of a presentation at the PIDS-St. Jude 2018 conference, PIDs for which transplants are increasingly performed outside of early childhood will be discussed.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes de Imunodeficiência/terapia , Criança , Deficiência de GATA2/terapia , Fatores de Troca do Nucleotídeo Guanina/deficiência , Humanos , Lactente , Imunodeficiência Combinada Severa/terapia
9.
Immunol Res ; 66(4): 537-542, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30084052

RESUMO

Newborn screening (NBS) programs for severe combined immunodeficiency (SCID), using the TREC-based assay, have enabled early diagnosis, prompt treatment, and eventually changed the natural history of affected infants. Nevertheless, it was believed that some affected infants with residual T cell, such as patients with MHC II deficiency, will be misdiagnosed by this assay. A full immune workup and genetic analysis using direct Sanger sequencing and whole exome sequencing have been performed to a patient that was identified by the Israeli NBS program for SCID. The patient was found to have severe CD4 lymphopenia with an inverted CD4/CD8 ratio, low TREC levels in peripheral blood, abnormal response to mitogen stimulation, and a skewed T cell receptor repertoire. HLA-DR expression on peripheral blood lymphocytes was undetectable suggesting a diagnosis of MHC II deficiency. Direct sequencing of the RFX5 gene revealed a stop codon change (p. R239X, c. C715T), which could cause the patient's immune phenotype. His parents were found to be heterozygote carriers for the mutation. Whole exome sequencing could not identify other potential mutations to explain his immunodeficiency. The patient underwent successful conditioned hematopoietic stem cell transplantation from healthy matched unrelated donor and is currently well and alive with full chimerism. Infants with MHC class II deficiency can potentially be identified by the TREC-based assay NBS for SCID. Therefore, MHC II molecules (e.g., HLA-DR) measurement should be part of the confirmatory immune-phenotyping for patients with positive screening results. This will make the diagnosis of such patients straightforward.


Assuntos
Linfócitos T CD4-Positivos/fisiologia , Antígenos HLA-DR/genética , Mutação/genética , Fatores de Transcrição de Fator Regulador X/genética , Imunodeficiência Combinada Severa/diagnóstico , Quimerismo , Consanguinidade , Análise Mutacional de DNA , Transplante de Células-Tronco Hematopoéticas , Humanos , Recém-Nascido , Israel , Linfopenia , Masculino , Triagem Neonatal , Receptores de Antígenos de Linfócitos T/genética , Imunodeficiência Combinada Severa/genética , Imunodeficiência Combinada Severa/terapia , Sequenciamento Completo do Exoma
10.
J Clin Immunol ; 38(6): 727-732, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30105620

RESUMO

Hematopoietic stem cell transplantation (HSCT) is curative for severe combined immunodeficiency (SCID), but data on long-term impact of pre-HSCT chemotherapy, immune reconstitution and quality of life (QoL) of specific SCID genotypes are limited. We evaluated the long-term immune-reconstitution, health outcome and QoL in IL7Rα SCID, Artemis and RAG1 and 2 SCID survivors > 2 years post-HSCT in our center. Clinical data and immune reconstitution parameters were collated, and patients/families answered PedsQL generic core scale v4.0 questionnaires. Thirty-nine patients with a diagnosis of IL7Rα SCID (17 patients), Artemis SCID (8 patients) and RAG1/2 SCID (13 patients) had undergone HSCT with median age at last follow up for IL7Rα SCID, 14 years (range 4-27) and Artemis and RAG1/2 SCID, 10 years (range 2-18). Many patients have ongoing medical issues at latest follow-up [IL7Rα (73%), Artemis (85%), RAG1/2 (55%)]. Artemis SCID patients experienced more sequela than RAG1/2 SCID. Conditioned recipients with Artemis and RAG SCID had more CD4+ naïve lymphocytes compared to unconditioned recipients. All patients except those of IL7Rα SCID reported lower QoL; further subset group analysis showed parents and Artemis and RAG1/2 survivors without ongoing medical issues reported normal QoL. Conditioned recipients have superior long-term thymopoiesis, chimerism and immunoglobulin-independence. QoL was normal in those who did not have medical issues at long-term follow-up.


Assuntos
Proteínas de Ligação a DNA/deficiência , Endonucleases/deficiência , Proteínas de Homeodomínio/genética , Proteínas Nucleares/deficiência , Qualidade de Vida , Receptores de Interleucina-7/deficiência , Imunodeficiência Combinada Severa/epidemiologia , Imunodeficiência Combinada Severa/etiologia , Adolescente , Adulto , Criança , Pré-Escolar , Suscetibilidade a Doenças , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Estudos Longitudinais , Masculino , Estudos Retrospectivos , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/terapia , Fatores de Tempo , Adulto Jovem
11.
Clin Immunol ; 197: 1-5, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30121298

RESUMO

V(D)J recombination, during which recognition and repair of broken DNA chains are accomplished by non-homologous end joining pathway, is a critical process in B and T cell development.Null mutations of each enzyme or protein of this pathway result in T- B- NK+ severe combined immunodeficiency whereas hypomorphic mutations result in atypical(leaky)severe combined immunodeficiency forms. We present two siblings with PRKDC (Protein Kinase, DNA-Activated, Catalytic Polypeptide) mutation who presented with granulomatous skin lesions and recurrent lung infections. Primary immune deficiencies may initially present with skin findings. Disruption in central and peripheral B-cell tolerance and impaired intrathymic T-cell maturation,a central player in T-cell tolerance, have been identified as the mechanism of autoimmunity and granuloma seen in patients. The variation in clinical phenotypes of patients with PRKDC mutation suggests that additional factors such as modifying genes, epigenetic and environmental factors may affect the severity and clinical phenotype of the disease. Functional studies during the follow-up and evaluation before and after hematopoeitic stem cell transplantation will hopefully increase our knowledge about the autoimmune and inflammatory process of the disease spectrum.


Assuntos
Proteína Quinase Ativada por DNA/genética , Granuloma/genética , Histiocitose de Células não Langerhans/genética , Proteínas Nucleares/genética , Imunodeficiência Combinada Severa/genética , Dermatopatias/genética , Pré-Escolar , Feminino , Granuloma/imunologia , Granuloma/patologia , Transplante de Células-Tronco Hematopoéticas , Histiocitose de Células não Langerhans/imunologia , Histiocitose de Células não Langerhans/patologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Lactente , Recém-Nascido , Pneumonia Bacteriana/genética , Pneumonia Bacteriana/imunologia , Imunodeficiência Combinada Severa/imunologia , Imunodeficiência Combinada Severa/patologia , Imunodeficiência Combinada Severa/terapia , Irmãos , Dermatopatias/imunologia , Dermatopatias/patologia
12.
Blood ; 132(17): 1737-1749, 2018 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-30154114

RESUMO

The Primary Immune Deficiency Treatment Consortium (PIDTC) performed a retrospective analysis of 662 patients with severe combined immunodeficiency (SCID) who received a hematopoietic cell transplantation (HCT) as first-line treatment between 1982 and 2012 in 33 North American institutions. Overall survival was higher after HCT from matched-sibling donors (MSDs). Among recipients of non-MSD HCT, multivariate analysis showed that the SCID genotype strongly influenced survival and immune reconstitution. Overall survival was similar for patients with RAG, IL2RG, or JAK3 defects and was significantly better compared with patients with ADA or DCLRE1C mutations. Patients with RAG or DCLRE1C mutations had poorer immune reconstitution than other genotypes. Although survival did not correlate with the type of conditioning regimen, recipients of reduced-intensity or myeloablative conditioning had a lower incidence of treatment failure and better T- and B-cell reconstitution, but a higher risk for graft-versus-host disease, compared with those receiving no conditioning or immunosuppression only. Infection-free status and younger age at HCT were associated with improved survival. Typical SCID, leaky SCID, and Omenn syndrome had similar outcomes. Landmark analysis identified CD4+ and CD4+CD45RA+ cell counts at 6 and 12 months post-HCT as biomarkers predictive of overall survival and long-term T-cell reconstitution. Our data emphasize the need for patient-tailored treatment strategies depending upon the underlying SCID genotype. The prognostic significance of CD4+ cell counts as early as 6 months after HCT emphasizes the importance of close follow-up of immune reconstitution to identify patients who may need additional intervention to prevent poor long-term outcome.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Transplante de Células-Tronco Hematopoéticas , Reconstituição Imune/imunologia , Imunodeficiência Combinada Severa/genética , Imunodeficiência Combinada Severa/mortalidade , Imunodeficiência Combinada Severa/terapia , Genótipo , Humanos , Contagem de Linfócitos , Estudos Retrospectivos
13.
J Clin Immunol ; 38(6): 646-655, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30046960

RESUMO

PURPOSE: To review the clinical and laboratory spectrum of RAG gene defects in humans, and discuss the mechanisms underlying phenotypic heterogeneity, the basis of immune dysregulation, and the current and perspective treatment modalities. METHODS: Literature review and analysis of medical records RESULTS: RAG gene defects in humans are associated with a surprisingly broad spectrum of clinical and immunological phenotypes. Correlation between in vitro recombination activity of the mutant RAG proteins and the clinical phenotype has been observed. Altered T and B cell development in this disease is associated with defects of immune tolerance. Hematopoietic cell transplantation is the treatment of choice for the most severe forms of the disease, but a high rate of graft failure has been observed. CONCLUSIONS: Phenotypic heterogeneity of RAG gene defects in humans may represent a diagnostic challenge. There is a need to improve treatment for severe, early-onset forms of the disease. Optimal treatment modalities for patients with delayed-onset disease presenting with autoimmunity and/or inflammation remain to be defined.


Assuntos
Proteínas de Ligação a DNA/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Proteínas de Homeodomínio/genética , Proteínas Nucleares/genética , Animais , Autoimunidade , Variação Biológica da População , Proteínas de Ligação a DNA/metabolismo , Proteínas de Homeodomínio/metabolismo , Humanos , Imunidade , Mutação , Proteínas Nucleares/metabolismo , Fenótipo , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/genética , Imunodeficiência Combinada Severa/imunologia , Imunodeficiência Combinada Severa/terapia
14.
Georgian Med News ; (279): 107-110, 2018 Jun.
Artigo em Russo | MEDLINE | ID: mdl-30035731

RESUMO

In connection with the urgency of early diagnosis of severe combined immune deficiency, the case from the clinical practice of the National Science Center for Maternity and Childhood, Astana, was considered. This clinical case indicates that it is difficult to verify the diagnosis of severe combined failure, as the child was hospitalized in city clinics with various infectious diseases before receiving the right treatment more than 10 times in 4 months of life. Also, this clinical example confirms that the most effective method of treating this disorder at the present stage is bone marrow transplantation. With all medical prescriptions and recommendations, a complete restoration of the immune system is possible.


Assuntos
Imunodeficiência Combinada Severa/diagnóstico , Teste em Amostras de Sangue Seco , Humanos , Lactente , Imunodeficiência Combinada Severa/imunologia , Imunodeficiência Combinada Severa/terapia , Transplante de Células-Tronco
16.
Iran J Allergy Asthma Immunol ; 17(2): 201-207, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29757593

RESUMO

Severe combined immunodeficiency syndrome (SCID) is a life-threatening condition leading to early infant death as a result of severe infection, due to impaired cellular and humoral immune systems. Various forms of SCID are classified based on the presence or absence of T cells, B cells and natural killer cells. Patients usually present with recurrent infections and failure to thrive. Definitive treatment is hematopoietic stem cell transplantation. To achieve the best outcome, it should be performed prior to the development of severe infection. In This study, we described 10 patients (6 male and 4 female) with SCID who were admitted to Mofid Children Hospital, Tehran, Iran, from 2006 to 2013. We reviewed patients' clinical manifestation, laboratory data, family history and outcome. The mean age at the time of diagnosis was 131.8 days. One patient had non-consanguineous parents. Seven patients received BCG vaccine before the diagnosis of SCID, three of them showed disseminated BCG infection. One patient presented with invasive pulmonary aspergillosis. Flow cytometric analysis showed T⁻B⁺NK⁻ in three patients, T⁻B⁻NK⁺ in five patients, T⁻B⁻NK⁻ in one patient, and T⁻B⁺NK⁺ in one patient. This study highlights the importance of early diagnosis and patient referral before the occurrence of serious infection.


Assuntos
Imunodeficiência Combinada Severa/epidemiologia , Vacina BCG/efeitos adversos , Suscetibilidade a Doenças , Feminino , Transplante de Células-Tronco Hematopoéticas , Hospitais Pediátricos , Humanos , Lactente , Recém-Nascido , Irã (Geográfico)/epidemiologia , Contagem de Linfócitos , Masculino , Estudos Retrospectivos , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/terapia , Resultado do Tratamento
18.
Blood ; 131(26): 2967-2977, 2018 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-29728406

RESUMO

Allogeneic hematopoietic stem cell transplant (HSCT) typically results in donor T-cell engraftment and function in patients with severe combined immunodeficiency (SCID), but humoral immunity, particularly when using donors other than matched siblings, is variable. B-cell function after HSCT for SCID depends on the genetic cause, the use of pre-HSCT conditioning, and whether donor B-cell chimerism is achieved. Patients with defects in IL2RG or JAK3 undergoing HSCT without conditioning often have poor B-cell function post-HSCT, perhaps as a result of impairment of IL-21 signaling in host-derived B cells. To investigate the effect of pre-HSCT conditioning on B-cell function, and the relationship of in vitro B-cell function to clinical humoral immune status, we analyzed 48 patients with IL2RG/JAK3 SCID who were older than 2 years after HSCT with donors other than matched siblings. T follicular helper cells (TFH) developed in these patients with kinetics similar to healthy young children; thus, poor B-cell function could not be attributed to a failure of TFH development. In vitro differentiation of B cells into plasmablasts and immunoglobulin secretion in response to IL-21 strongly correlated with the use of conditioning, donor B-cell engraftment, freedom from immunoglobulin replacement, and response to tetanus vaccine. Patients receiving immunoglobulin replacement who had normal serum immunoglobulin M showed poor response to IL-21 in vitro, similar to those with low serum IgM. In vitro response of B cells to IL-21 may predict clinically relevant humoral immune function in patients with IL2RG/JAK3 SCID after HSCT.


Assuntos
Linfócitos B/imunologia , Transplante de Células-Tronco Hematopoéticas/métodos , Subunidade gama Comum de Receptores de Interleucina/imunologia , Interleucinas/imunologia , Janus Quinase 3/imunologia , Imunodeficiência Combinada Severa/terapia , Condicionamento Pré-Transplante/métodos , Adolescente , Linfócitos B/citologia , Diferenciação Celular , Criança , Pré-Escolar , Feminino , Humanos , Imunidade Humoral , Subunidade gama Comum de Receptores de Interleucina/genética , Janus Quinase 3/genética , Ativação Linfocitária , Masculino , Imunodeficiência Combinada Severa/genética , Imunodeficiência Combinada Severa/imunologia , Linfócitos T/imunologia , Transplante Homólogo , Adulto Jovem
19.
Immunol Res ; 66(3): 437-443, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29804197

RESUMO

Infants with severe combined immunodeficiency (SCID) are at risk of developing severe life-threatening infections if they are inadvertently given attenuated live vaccines. Concomitant appearance of two live vaccine-associated complications in one person is rarely reported. In this study, we present two SCID infants, who received BCG and oral polio vaccines according to their local immunization schedule early in life, before the diagnosis of immunodeficiency was made. Their clinical presentation, extensive immunological workup, genetic tests, and clinical disease course are presented. Both patients developed localized and disseminated infections originating from the BCG vaccine (BCGitis and BCGiosis, respectively) and in addition suffered from diarrhea and chronic fecal secretion of vaccine-derived poliovirus. Alarmingly, in case 2, the poliovirus was a type 2 vaccine-derived poliovirus in which both neurovirulence attenuation sites reverted to the neurovirulent genotype. These cases highlight the importance of early recognition of SCID by neonatal screening or thorough family anamnesis, and the need to further defer the timing of administration of attenuated live vaccines.


Assuntos
Vacina BCG/efeitos adversos , Vacina Antipólio Oral/efeitos adversos , Imunodeficiência Combinada Severa/diagnóstico , Vacinas Atenuadas/efeitos adversos , Vacina BCG/imunologia , Transplante de Medula Óssea/métodos , Fezes/virologia , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Mycobacterium bovis/imunologia , Mycobacterium bovis/isolamento & purificação , Poliovirus/imunologia , Vacina Antipólio Oral/imunologia , Imunodeficiência Combinada Severa/etiologia , Imunodeficiência Combinada Severa/terapia , Transplante Homólogo , Resultado do Tratamento , Vacinas Atenuadas/imunologia
20.
Antivir Ther ; 23(6): 505-511, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29790481

RESUMO

BACKGROUND: Cytomegalovirus (CMV) infection is a major risk factor for mortality in infants with severe combined immunodeficiency (SCID) and other profound immune defects. Specific antiviral therapy must be initiated early and aggressively because of the potential for antiviral resistance, rapid dissemination and poor transplant outcomes. Combination antiviral therapy is routinely administered for some viral infections, but the value of this approach for the treatment of CMV is unclear. Here we explore a strategy of initial combination therapy for high-risk infants with CMV infection. METHODS: We reviewed medical records of infants ≤6 months of age hospitalized between 2007-2015 who received ganciclovir (GCV) or foscarnet (FOS) monotherapy or initial combination GCV + FOS for CMV disease. The combination therapy group consisted of severely immunocompromised infants being considered for haematopoietic cell transplantation (HCT). RESULTS: Four patients received initial combination antiviral therapy and 26 patients received initial monotherapy during the study period. Combination antiviral recipients demonstrated initial improvement in viraemia and two of three who continued with this therapy survived the infection. Clinically significant resistance mutations did not emerge. Toxicity was common; neutropenia, thrombocytopenia and electrolyte abnormalities were the most frequent adverse events in both groups. Creatinine elevation was uncommon in both groups. CONCLUSIONS: Combination GCV + FOS therapy may be a safe alternative to monotherapy in high-risk infants, especially those who are pre-transplant with primary immune deficiency syndromes and high viral loads.


Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/tratamento farmacológico , Foscarnet/uso terapêutico , Ganciclovir/uso terapêutico , Hospedeiro Imunocomprometido , Imunodeficiência Combinada Severa/imunologia , Viremia/tratamento farmacológico , Citomegalovirus/efeitos dos fármacos , Citomegalovirus/imunologia , Citomegalovirus/patogenicidade , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/mortalidade , Infecções por Citomegalovirus/virologia , Quimioterapia Combinada , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Fatores de Risco , Imunodeficiência Combinada Severa/mortalidade , Imunodeficiência Combinada Severa/terapia , Imunodeficiência Combinada Severa/virologia , Análise de Sobrevida , Carga Viral/efeitos dos fármacos , Viremia/imunologia , Viremia/mortalidade , Viremia/virologia
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