RESUMEN
INTRODUCTION: Autosomal recessively inherited lipopolysaccharide-responsive beige-like anchor (LRBA) protein deficiency was shown to be responsible for different types of inborn errors of immunity, such as common variable immunodeficiency (CVID) and autoimmune lymphoproliferative syndrome (ALPS). The aim of this study was to compare patients with LRBA-related ALPS and LRBA-related CVID, to describe their clinical and laboratory phenotypes, and to prepare an algorithm for their diagnosis and management. METHODS: Fifteen LRBA-deficient patients were identified among 31 CVID and 14 possible ALPS patients with Western blotting (WB), primary immunodeficiency disease (PIDD) gene, next-generation panel screening (NGS), and whole exome sequencing (WES). RESULTS: The median age on admission and age of diagnosis were 7 years (0.3-16.5) and 11 years (5-44), respectively. Splenomegaly was seen in 93.3% (14/15) of the patients on admission. Splenectomy was performed to 1/5. Recurrent upper respiratory tract infections (93.3% (14/15)), autoimmune cytopenia (80% (12/15)), chronic diarrhea (53.3% (8/15)), lower respiratory tract infections (53.3% (8/15)), lymphoma (26.6% (4/15)), Evans syndrome (26.6% (4/15)), and autoimmune thyroiditis (20% (3/15)) were common clinical findings and diseases. Lymphopenia (5/15), intermittant neutropenia (4/15), eosinophilia (4/15), and progressive hypogammaglobulinemia are recorded in given number of patients. Double negative T cells (TCRαß+CD4-CD8-) were increased in 80% (8/10) of the patients. B cell percentage/numbers were low in 60% (9/15) of the patients on admission. Decreased switched memory B cells, decreased naive and recent thymic emigrant (RTE) Thelper (Th) cells, markedly increased effector memory/effector memory RA+ (TEMRA) Th were documented. Large PD1+ population, increased memory, and enlarged follicular helper T cell population in the CD4+ T cell compartment was seen in one of the patients. Most of the deleterious missense mutations were located in the DUF1088 and BEACH domains. Interestingly, one of the two siblings with the same homozygous LRBA defect did not have any clinical symptom. Hematopoietic stem cell transplantation (HSCT) was performed to 7/15 (46.6%) of the patients. Transplanted patients are alive and well after a median of 2 years (1-3). In total, one patient died from sepsis during adulthood before HSCT. CONCLUSION: Patients with LRBA deficiency may initially be diagnosed as CVID or ALPS in the clinical practice. Progressive decrease in B cells as well as IgG in ALPS-like patients and addition of IBD symptoms in the follow-up should raise the suspicion for LRBA deficiency. Decreased switched memory B cells, decreased naive and recent thymic emigrant (RTE) Th cells, and markedly increased effector memory/effector memory RA+ Th cells (TEMRA Th) cells are important for the diagnosis of the patients in addition to clinical features. Analysis of protein by either WB or flow cytometry is required when the clinicians come across especially with missense LRBA variants of uncertain significance. High rate of malignancy shows the regulatory T cell's important role of immune surveillance. HSCT is curative and succesful in patients with HLA-matched family donor.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/deficiencia , Síndrome Linfoproliferativo Autoinmune/diagnóstico , Síndrome Linfoproliferativo Autoinmune/etiología , Inmunodeficiencia Variable Común/diagnóstico , Inmunodeficiencia Variable Común/etiología , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adolescente , Adulto , Síndrome Linfoproliferativo Autoinmune/complicaciones , Síndrome Linfoproliferativo Autoinmune/terapia , Biomarcadores , Niño , Preescolar , Terapia Combinada , Inmunodeficiencia Variable Común/complicaciones , Inmunodeficiencia Variable Común/terapia , Enfermedades Transmisibles/etiología , Femenino , Estudios de Asociación Genética/métodos , Sitios Genéticos , Trasplante de Células Madre Hematopoyéticas , Humanos , Inmunofenotipificación , Masculino , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Resultado del Tratamiento , Secuenciación del Exoma , Adulto JovenRESUMEN
Vincristine commonly induces peripheral neuropathy but rarely causes voiding dysfunction. In this report, we describe a case of neurogenic bladder and peripheral neuropathy caused by the neurotoxic effect of vincristine and documented by urodynamic testing and electromyography. Neurologic evaluation aided in monitoring and understanding this problem.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Parálisis/inducido químicamente , Rabdomiosarcoma/complicaciones , Vejiga Urinaria Neurogénica/inducido químicamente , Vincristina/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Niño , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Dactinomicina/administración & dosificación , Dactinomicina/efectos adversos , Electromiografía , Humanos , Masculino , Monitoreo Fisiológico , Rabdomiosarcoma/tratamiento farmacológico , Urodinámica , Vincristina/administración & dosificaciónRESUMEN
The aim of this study was to evaluate and compare the clinical characteristics of the B-cell non-Hodgkin lymphoma (NHL) patients and therapeutic efficacy of modified NHL BFM-90 and NHL BFM-95 protocols in the authors' center. From January 1993 to December 2003, 61 newly diagnosed children with B-NHL were enrolled to the study. The patients were stratified by risk factors and treated either with a modified B-NHL BFM-90 or BFM-95 protocols. The use of 1 or 3 g/m2 of methotrexate instead of 5 g/m2/24 h was the only important modification in BFM-90 protocol. Sixty-one children (12 girls, 49 boys) with a median age of 6.5 years (range: 2.5-16) were treated in the center. There were 14 patients in stage II, 28 in stage III, and 19 in stage IV. The most common initial primary tumor sites were abdomen, head, and neck. Forty-five patients were treated with modified B-cell BFM-90 and 16 patients were treated with B-cell BFM-95 regimens. The 5-year overall survival (OS) for all patients was 85.8%, and event-free survival (EFS) was 82.8%. The 5-year OS rates in modified BFM-90 and in BFM-95 protocols were 85.2 and 87.5%; the 5-year EFS rates in these 2 protocols were 84.6 and 70%, respectively (p >.05). Factors associated with lower EFS by univariate analysis were bulky disease, risk groups, and LDH level > or = 500 IU/L. By multivariate analysis only LDH level was significant. In conclusion, the treatment results in this study were similar to those of BFM group.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B/tratamiento farmacológico , Adolescente , Alopurinol/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Niño , Preescolar , Supervivencia sin Enfermedad , Diuréticos/uso terapéutico , Femenino , Fluidoterapia , Enfermedades Hematológicas/inducido químicamente , Humanos , Estimación de Kaplan-Meier , L-Lactato Deshidrogenasa/sangre , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Linfoma de Células B/sangre , Linfoma de Células B/mortalidad , Linfoma de Células B/patología , Masculino , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Mucositis/inducido químicamente , Proteínas de Neoplasias/sangre , Medición de Riesgo , Bicarbonato de Sodio/uso terapéutico , Análisis de Supervivencia , Tasa de Supervivencia , Resultado del Tratamiento , Carga Tumoral , Síndrome de Lisis Tumoral/prevención & control , Turquía/epidemiología , Vincristina/administración & dosificación , Vincristina/efectos adversosRESUMEN
Nodular regenerative hyperplasia (NRH) and focal nodular hyperplasia (FNH) of the liver rarely occur in children after completion of tumor therapy. These lesions mimic hepatic metastasis and they must be distinguished from metastatic lesions. The authors present 2 children, one with NRH and one with FNH, after undergoing antineoplastic therapy for non-hepatic childhood solid tumors and discuss their patients in the context of the literature.
Asunto(s)
Hiperplasia Nodular Focal/diagnóstico , Hepatopatías/diagnóstico , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundario , Adolescente , Antineoplásicos/uso terapéutico , Preescolar , Diagnóstico Diferencial , Diagnóstico por Imagen , Femenino , Humanos , MasculinoRESUMEN
Here we describe a case of a neuroblastoma patient with recurrent vancomycin-resistant enterococcal infection successfully treated with ciprofloxacin. This is the first case of recurrent vancomycin-resistant enterococcal infection in our hospital and Turkey.
Asunto(s)
Ciprofloxacina/uso terapéutico , Enterococcus faecium/efectos de los fármacos , Infecciones por Bacterias Grampositivas/microbiología , Resistencia a la Vancomicina , Antibacterianos/farmacología , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Preescolar , Femenino , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/epidemiología , Humanos , Turquía/epidemiologíaRESUMEN
In this report we describe an unusual case of neuroblastoma that presented with an initial manifestation of protein losing enteropathy secondary to intestinal lymphangiectasia.
Asunto(s)
Neoplasias Abdominales/complicaciones , Linfangiectasia Intestinal/etiología , Neuroblastoma/complicaciones , Enteropatías Perdedoras de Proteínas/etiología , Neoplasias Abdominales/patología , Resultado Fatal , Femenino , Humanos , Lactante , Linfangiectasia Intestinal/patología , Neuroblastoma/patología , Enteropatías Perdedoras de Proteínas/patologíaRESUMEN
Anterior mediastinal and adenoid masses in children after cessation of chemotherapy for malignant disease often cause a diagnostic problem. Differential diagnosis of thymic enlargement and adenoid hyperplasia from recurrence frequently poses a challenge both for the radiologist and the physician. In this study the authors evaluated 491 patients with different malignant tumors for thymic and adenoid hyperplasia. Thymic hyperplasia was seen in 18 patients (5 Hodgkin disease (HD), 5 non-Hodgkin lymphoma (NHL), 4 Wilms tumor, 2 germ cell tumor, 1 Ewing sarcoma, and 1 neuroblastoma), only adenotonsillar hyperplasia was seen in 6 patients, all with NHL, and both thymic and adenotonsillar hyperplasia were seen in 3 patients (1 HD, 2 NHL). In 5 patients, adenoid hyperplasia was proven by biopsy; 1 patient underwent to adenoidectomy. Their histopathologic investigation showed polyclonal follicular hyperplasia. The authors recommend that patients with thymic and/or adenotonsillar enlargement after successful treatment of their primary malignancy should be evaluated cautiously before an invasive procedure is planned.