RESUMO
INTRODUCTION: Ependymomas in the posterior fossa have poor prognosis. This study reports a single-center pediatric series, focusing on the value of surgical resection. MATERIAL AND METHODS: A single-center retrospective study included all patients operated on by the senior author (CM) for posterior fossa ependymoma from 2002 to 2018. Medical and surgical data were extracted from the hospital's medical database. RESULTS: Thirty-four patients were included. Age ranged from 6 months to 18 years, with a median of 4.7 years. Fourteen patients underwent initial endoscopic third ventriculocisternostomy before the direct surgical resection. Surgical removal was complete in 27 patients. There were 32 surgeries for second-look, local recurrence or metastasis despite complementary chemotherapy and/or radiotherapy. Twenty patients were WHO grade 2 and 14 grade 3. Sixteen patients showed recurrence (47%). Overall survival was 61.8% at a mean 10.1 years' follow-up. Morbidities comprised facial nerve palsy, swallowing disorder, and transient cerebellar syndrome. Fifteen patients had normal schooling, 6 had special assistance; 4 patients reached university, 3 of whom experienced difficulties. Three patients had a job. CONCLUSION: Posterior fossa ependymomas are aggressive tumors. Complete surgical removal is the most important prognostic factor, despite risk of sequelae. Complementary treatment is mandatory, but no targeted therapy has so far proved effective. It is important to continue the search for molecular markers in order to improve outcomes.
Assuntos
Ependimoma , Criança , Humanos , Lactente , Estudos Retrospectivos , Ependimoma/diagnóstico , Ependimoma/cirurgia , Terapia Combinada , Progressão da DoençaRESUMO
INTRODUCTION: Modern approach for the treatment of posterior fossa medulloblastomas remains a challenge for pediatric neurosurgeons and pediatric oncologists and requires a multidisciplinary approach to optimize survival and clinical results. MATERIAL AND METHODS: We report the surgical principles of the treatment of posterior fossa medulloblastomas in children and how to avoid technical mistakes especially in very young patients. We also report our experience in a series of 64 patients operated from a medulloblastoma between 2000 and 2018 in Lyon. RESULTS: All patients had a craniospinal MRI. Eighty-one percent of the patients (n=50) had strictly midline tumor while 19% (n=14) had lateralized one. Eleven percent (n=7) had metastasis at diagnosis on the initial MRI. Forty-one percent (n=29) had an emergency ETV to treat hydrocephaly and the intracranial hypertension. All patient underwent a direct approach and a complete removal was achieved in 78% (n=58) of the cases on the postoperative MRI realized within 48h postsurgery. Histological findings revealed classical medulloblastoma in 73% (n=46), desmoplastic medulloblastoma in 17% (n=11) and anaplastic/large cell medulloblastoma in 10% (n=7). Patients were classified as low risk in 7 cases, standard risk in 30 cases and high risk in 27 cases. Ninety-six percent (n=61) of the patient received radiotherapy. Seventy-six percent (n=48) received pre-irradiation or adjuvant chemotherapy. At last follow-up in December 2018, 65% (n=41) of the patient were in complete remission, 12% (n=8) were in relapse and 27% (n=15) had died from their disease. The overall survival at five , ten and fifteen years for all the series was of 76%, 73% and 65.7% respectively. CONCLUSIONS: Medulloblastomas remain a chimiosensible and radiosensible disease and the complete surgical removal represents a favorable prognostic factor. The extension of surgery has also to be weighted in consideration of the new biomolecular and genetic knowledge that have to be integrated by surgeons to improve quality of life of patients.
Assuntos
Neoplasias Cerebelares/epidemiologia , Neoplasias Cerebelares/cirurgia , Fossa Craniana Posterior/cirurgia , Meduloblastoma/epidemiologia , Meduloblastoma/cirurgia , Adolescente , Neoplasias Cerebelares/diagnóstico por imagem , Quimioterapia Adjuvante/métodos , Criança , Pré-Escolar , Fossa Craniana Posterior/diagnóstico por imagem , Feminino , França/epidemiologia , Humanos , Lactente , Masculino , Meduloblastoma/diagnóstico por imagem , Estadiamento de Neoplasias/métodos , Qualidade de VidaRESUMO
Medulloblastomas present generally a-specifically as a fast-evolving posterior fossa tumor. Medical literature is poor concerning clinical features of medulloblastomas and their potential significance. In the present study, we reviewed 91 pediatric observations of medulloblastomas treated in Lille between 1997 and 2017. Clinical and epidemiological variables were collected and intercorrelated. They were also compared with anatomical and pathological findings, and outcome, with the aim of defining clinical-pathological entities. We also compared the group with 32 cases of posterior fossa ependymoma and 130 cases of cerebellar astrocytoma treated during the same period. We found that in medulloblastomas, the M/F ratio was higher and diagnostic delay was shorter than in astrocytomas. Also, the mean age was older than in ependymomas. Intracranial hypertension was constant; we further observed that altered general status was common (16.5%) and correlated with a metastatic tumor. We delineated two clusters: the "nodular" cluster, which associates young age, cerebello-pontine angle tumor, herniation, desmoplastic tumor, and tumor predisposition syndrome; and the "metastatic" cluster, which associates altered status, initial metastases, hydrocephalus, and diagnostic delay. Meticulous collection of clinical data at the initial phase is integral part of the oncological evaluation, with a search for genetic and prognostic risk factors, which then permits us to define clinical-pathological entities.
Assuntos
Neoplasias Cerebelares/diagnóstico por imagem , Diagnóstico Tardio , Neoplasias Infratentoriais/diagnóstico por imagem , Meduloblastoma/diagnóstico por imagem , Adolescente , Neoplasias Cerebelares/genética , Neoplasias Cerebelares/cirurgia , Criança , Pré-Escolar , Diagnóstico Tardio/tendências , Feminino , Seguimentos , Humanos , Hidrocefalia/diagnóstico por imagem , Hidrocefalia/genética , Hidrocefalia/cirurgia , Lactente , Neoplasias Infratentoriais/genética , Neoplasias Infratentoriais/cirurgia , Masculino , Meduloblastoma/genética , Meduloblastoma/cirurgia , PrognósticoAssuntos
Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Lobo Frontal/patologia , Tumor Rabdoide/patologia , Astrocitoma/diagnóstico por imagem , Astrocitoma/cirurgia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Criança , Feminino , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/cirurgia , Humanos , Lactente , Imageamento por Ressonância Magnética , Tumor Rabdoide/diagnóstico por imagem , Tumor Rabdoide/cirurgia , Resultado do TratamentoRESUMO
The aim of this study was to review and describe therapeutic approaches in children with choroid plexus tumor (CPT) based on a nationwide series. The World Health Organization classification subdivides these rare tumors into three histological subtypes corresponding to three grades of malignancy: low grade (grade I) choroid plexus papilloma (CPP), intermediate grade (grade II) atypical choroid plexus papilloma (aCPP) and high grade (grade III) choroid plexus carcinoma (CPC). This retrospective study included 102 French children younger than 18 years, treated from 2000 to 2012: 54 CPP, 26 aCPP and 22 CPC. The 5 year overall survival was 100% in CPP, 96.2% in aCPP and 64.7% in CPC. In patients with localized disease, complete surgical resection was achieved in 48/52 CPP, 20/26 aCPP and 7/14 CPC. In this group, patients with complete surgical resection had better event free survival than patients with partial resection (88.9 vs. 41.6%). 28 patients (1 CPP, 6 aCPP and 22 CPC) had adjuvant chemotherapy. 2 aCPP and 9 CPC had radiotherapy. We underlined the need for a central histological review to accurately analyze clinical data; we reported a much higher overall survival for CPC than in most previous CPT series probably including atypical teratoid rhabdoid tumors. In our series, the 5 years overall survival in CPC (64.7%) was higher than event free survival (25.2%) and could be interpreted as a clue for the efficiency of adjuvant/salvage therapy even if the heterogeneity of applied treatments in this retrospective series does not allow for meaningful statistical comparisons.
Assuntos
Carcinoma/terapia , Neoplasias do Plexo Corióideo/terapia , Papiloma do Plexo Corióideo/terapia , Tumor Rabdoide/terapia , Teratoma/terapia , Adolescente , Carcinoma/genética , Carcinoma/patologia , Criança , Pré-Escolar , Neoplasias do Plexo Corióideo/genética , Neoplasias do Plexo Corióideo/patologia , Feminino , Seguimentos , França , Humanos , Lactente , Masculino , Gradação de Tumores , Papiloma do Plexo Corióideo/genética , Papiloma do Plexo Corióideo/patologia , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Tumor Rabdoide/genética , Tumor Rabdoide/patologia , Análise de Sobrevida , Teratoma/genética , Teratoma/patologia , Resultado do TratamentoRESUMO
OBJECTIVE: Desmoid tumours of the head and neck in children are rare, local invasive and potentially fatal tumours. The purpose of this review is to discuss the management of these tumours in the light of a case series and a review of the literature. MATERIAL AND METHODS: This retrospective study summarised the medical data of children treated for desmoid tumours of the head and neck between 1976 and 2014. RESULTS: Five of the 6 children were treated by radical surgical resection, with positive surgical margins (R1) in 2 cases, followed by recurrence requiring further resection. One child with a very advanced lesion was treated by weekly methotrexate and vinorelbine chemotherapy for 18months, allowing 93% reduction of tumour volume without recurrence. CONCLUSIONS: Desmoid tumours of the head and neck in children are more aggressive than their adult counterparts and are associated with high morbidity and mortality and a high recurrence rate. CT and MRI imaging assessment should preferably be performed before biopsy. External beam radiotherapy must be avoided in children as it is less effective than in adults, and is responsible for long-term cosmetic and functional sequelae and even a risk of second tumours. Treatment is surgical whenever radical resection is possible. In patients presenting an excessive risk of morbidity and mortality, chemotherapy devoid of long-term adverse effects (such as methotrexate in combination with a Vinca alkaloid) can be proposed. Long-term follow-up must be ensured due to the risk of recurrence.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fibromatose Agressiva/patologia , Fibromatose Agressiva/terapia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Adolescente , Criança , Pré-Escolar , Feminino , Fibromatose Agressiva/mortalidade , Fibromatose Agressiva/cirurgia , Seguimentos , França , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Lactente , Recém-Nascido , Masculino , Invasividade Neoplásica , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The pathophysiology of Thrombotic Thrombocytopenia Purpura (TTP) has been questioned since described in 1924. In 1998, Tsai [1] and Furlan [2] demonstrated a relationship of low levels of ADAMTS-13 with an IgG inhibitor in acquired idiopathic TTP. This study reports on a series of TTP patients treated with solvent/detergent plasma (SDP) or cryosupernatant plasma (CSP) and focuses on the correlation of their presentation, clinical response and outcome with the levels of ADAMTS-13, the inhibitor and VWF multimers. METHODS: Plasma exchange was carried out in patients with the clinical diagnosis of acquired idiopathic TTP. ADAMTS-13 enzyme activity and inhibitor levels, VWF multimers and platelet count were analyzed in correlation with patient outcome. This RCT was intended to compare outcome in 280 patients treated either with cryosupernatant or solvent-detergent heated plasmas. The primary end point was survival at six months. RESULTS: Data on 61 TTP patients were obtained from 16 centres across Canada. The study was then closed prematurely due to removal of one of the interventional products from the market. ADAMTS-13 enzyme activity and inhibitor levels varied considerably among study participants. At baseline, only 12/49 (24.5%) had ≤10% enzyme activity and 20/49 (41%) had levels ≥80%; whereas 16/49 had ≥80% inhibitors; 19/49 had ≤10% inhibitors 18/49 (37%) had no inhibitors. No unusually large VWF multimers were identified in any of the patients at presentation. The 6-month, all-cause mortality rates for patients randomized to receive CSP vs. SDP were 3/34 (9%; 95% CI: 3%, 23%) and 1/27 (4%; 95% CI: 1%, 18%), respectively, with a difference of 5% (95% CI: -11%, 20%). CONCLUSION: Although this study was underpowered to compare solvent/detergent vs. cryosupernatant plasma, our data suggest that ADAMTS-13 activity and inhibitor level at baseline cannot differentiate TTP response to plasma exchange therapy.
Assuntos
Proteínas ADAM/metabolismo , Troca Plasmática/métodos , Púrpura Trombocitopênica Trombótica/enzimologia , Púrpura Trombocitopênica Trombótica/terapia , Proteína ADAMTS13 , Adulto , Transfusão de Componentes Sanguíneos/métodos , Progressão da Doença , Feminino , Humanos , Masculino , Contagem de Plaquetas , Púrpura Trombocitopênica Trombótica/sangue , Resultado do Tratamento , Fator de von Willebrand/metabolismoRESUMO
Tumors of the lateral ventricle are not as rare in children as in adults and present complex problems which are to be dealt with often in a context of emergency, on account of their large size and the risk of life-threatening bleeding in a small child. Their diagnostic features are different in children, especially in infants and even more so in the fetus. The main surgical problems are the risk of bleeding and of hydraulic complications. From an oncological perspective, the main tumor types are choroid plexus tumors, subependymal giant-cell astrocytoma, and low-grade gliomas. The developmental outcome of these patients is often poor, on account of severe intracranial hypertension and young age at diagnosis.
Assuntos
Neoplasias do Ventrículo Cerebral/cirurgia , Ventrículos Laterais/cirurgia , Neoplasias do Ventrículo Cerebral/patologia , Criança , Neoplasias do Plexo Corióideo/complicações , Neoplasias do Plexo Corióideo/cirurgia , Humanos , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Hipertensão Intracraniana/complicações , Ventrículos Laterais/patologia , Imageamento por Ressonância Magnética , Procedimentos Neurocirúrgicos/métodos , Hemorragia Pós-Operatória/epidemiologia , Hemorragia Pós-Operatória/prevenção & controle , Risco , Tomografia Computadorizada por Raios XRESUMO
Scurvy, a disease related to ascorbic acid deficiency, remains rare in industrial countries. Ascorbic acid is a vitamin that intervenes most notably in the synthesis of collagen and catecholamines. We report the case of a 2-year-old boy hospitalized in a pediatric oncology unit because of an unusual presentation of scurvy revealed by pain and a significant increase in urinary catecholamine levels, raising fear of a neuroblastoma.
Assuntos
Neoplasias Musculares/diagnóstico , Neuroblastoma/diagnóstico , Escorbuto/diagnóstico , Pré-Escolar , Diagnóstico Diferencial , Humanos , MasculinoRESUMO
Despite the numerous clinical trials undertaken, the prognosis of children with diffuse brain stem glioma remains very poor. This review examines the different strategies for the treatment of malignant brain stem glioma such as radiation therapy, concurrent radiochemotherapy, and classical cytotoxic drugs, with a particular focus on the novel targeted and antiangiogenic drugs recently introduced in pediatric oncology. The strategy using integrin inhibitors is discussed.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias do Tronco Encefálico/tratamento farmacológico , Neoplasias do Tronco Encefálico/radioterapia , Glioma/tratamento farmacológico , Glioma/radioterapia , Inibidores da Angiogênese/uso terapêutico , Neoplasias do Tronco Encefálico/diagnóstico , Criança , Terapia Combinada , Irradiação Craniana , Glioma/diagnóstico , Humanos , Prognóstico , Radioterapia AdjuvanteRESUMO
Anticancer chemotherapy plays a key role in the treatment of cancer in children. Following its increased efficacy, three children out of four can now be cured. Nevertheless, given the fact that 25% of the children with cancer are not cured and chemotherapy-induced long-term side effects are numerous there is a need to keep developing new agents and new strategies to fight cancer. Moreover studies investigating off-patents drugs should be stimulated in paediatric oncology in order to improve our knowledge of "old" drugs. Here we will review the specificities of children as compared to adults in the context of clinical drug development and pharmacology research in paediatric oncology. Such a research is now encouraged and facilitated by a European regulation as well as by international consortia such as "Innovative Therapies for Children with Cancer" (ITCC).
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Fatores Etários , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/farmacocinética , Peso Corporal , Criança , Pré-Escolar , Comportamento Cooperativo , Indústria Farmacêutica , Ética Médica , Humanos , Lactente , Oncologia , Neoplasias/metabolismo , Neoplasias/mortalidade , Farmacogenética , Prognóstico , Projetos de Pesquisa/legislação & jurisprudênciaRESUMO
This chapter presents guidelines for the follow-up of children with brain tumors, whether benign or malignant, in their transition to adulthood. The consequences of their disease and its treatment overlap greatly. The complications and long-term follow-up are detailed based on the specialists involved.
Assuntos
Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Procedimentos Neurocirúrgicos , Adolescente , Adulto , Neoplasias Encefálicas/psicologia , Sistema Cardiovascular/crescimento & desenvolvimento , Sistema Cardiovascular/fisiopatologia , Criança , Glândulas Endócrinas/patologia , Glândulas Endócrinas/fisiopatologia , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Desenvolvimento Maxilofacial/fisiologia , Neoplasias Induzidas por Radiação/patologia , Neoplasias Induzidas por Radiação/cirurgia , Doenças do Sistema Nervoso/patologia , Doenças do Sistema Nervoso/fisiopatologia , Qualidade de Vida , Radiocirurgia/efeitos adversos , Sistema Respiratório/crescimento & desenvolvimento , Sistema Respiratório/fisiopatologia , Adulto JovemRESUMO
We report a case of neuroblastoma diagnosed after adrenal haemorrhage following a minor trauma in a thirteen-month-old boy. Minor trauma is not commonly described as a cause of AH in the literature. Therefore when no accepted cause for AH can be found in a young child below the age of 5 years, it is important to look for a neuroblastoma and discuss the necessity of surgical exploration.
Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Hemorragia/etiologia , Neuroblastoma/diagnóstico , Acidentes por Quedas , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/cirurgia , Glândulas Suprarrenais/irrigação sanguínea , Evolução Fatal , Humanos , Lactente , Masculino , Neuroblastoma/complicações , Neuroblastoma/genética , Neuroblastoma/cirurgia , Tomografia Computadorizada por Raios XRESUMO
Targeting of proteins for structure determination in structural genomic programs often includes the use of threading and fold recognition methods to exclude proteins belonging to well-populated fold families, but such methods can still fail to recognize preexisting folds. The authors illustrate here a method in which limited amounts of structural data are used to improve an initial homology search and the data are subsequently used to produce a structure by data-constrained refinement of an identified structural template. The data used are primarily NMR-based residual dipolar couplings, but they also include additional chemical shift and backbone-nuclear Overhauser effect data. Using this methodology, a backbone structure was efficiently produced for a 10 kDa protein (PF1455) from Pyrococcus furiosus. Its relationship to existing structures and its probable function are discussed.
Assuntos
Proteínas Arqueais/química , Modelos Moleculares , Ressonância Magnética Nuclear Biomolecular , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Pyrococcus furiosus/química , Homologia Estrutural de ProteínaRESUMO
BACKGROUND: Acute pyelonephritis can induce parenchymal scarring. The aim of this study was to evaluate the usefulness of procalcitonin (PCT) to predict renal involvement in febrile children with urinary tract infection (UTI). METHODS: In a prospective study serum PCT was measured and compared with others commonly used inflammatory markers in children admitted to the emergency unit with acute pyelonephritis. Renal parenchymal involvement was assessed by a (99 m)Tc-labeled dimercaptosuccinic acid (DMSA) renal scar performed in the first 3 days after the admission. RESULTS: Among 42 enrolled patients, 19 (45%) had acute renal involvement (Group A) ; 23 (55%) (Group B) had normal DMSA scan (n = 16), or old scarring (n = 4) or various anomalies related to uropathy (n = 3). In group A, the mean PCT level was significantly higher than in the group B (5.4 ng/ml, vs 0.4 ng /ml, p < 10(-5)). In these 2 groups, mean C reactive protein (CRP) levels were 99.1 mg/l and 44.6 mg/l respectively (p < 0.001). For a level of serum PCT > or = 0.5 ng/ml, the sensitivity and specificity to predict the renal involvement were 100% and 87% respectively; for a level> or= 20 mg/l CRP had a sensitivity of 94% but a specificity of 30%. CONCLUSION: Serum PCT levels were significantly increased in febrile children with UTI when acute renal parenchymal involvement was present. PCT seems a better marker than CRP for the prediction of patients at risk of renal lesions.
Assuntos
Calcitonina/sangue , Precursores de Proteínas/sangue , Pielonefrite/sangue , Pielonefrite/diagnóstico , Algoritmos , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Peptídeo Relacionado com Gene de Calcitonina , Criança , Pré-Escolar , Feminino , Febre/etiologia , França , Humanos , Lactente , Recém-Nascido , Masculino , Reação em Cadeia da Polimerase/métodos , Estudos Prospectivos , Pielonefrite/complicações , Pielonefrite/diagnóstico por imagem , Pielonefrite/patologia , Cintilografia , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade , Ácido Dimercaptossuccínico Tecnécio Tc 99mRESUMO
UNLABELLED: We report a case of idiopathic hypereosinophilic syndrome in a young child with favorable outcome after treatment with alpha-interferon. CASE REPORT: A 5-month-old boy presented with major eosinophilia (187 G/l) associated with splenomegaly. There was no evidence for parasitic or allergic disease. Acute leukemia was suspected but bone marrow smear and medullary caryotype were not compatible. Idiopathic hypereosinophilic syndrome was thus diagnosed. Corticotherapy was started and failed. Finally, complete remission was obtained with alpha-interferon treatment. CONCLUSION: Idiopathic hypereosinophilic syndrome is uncommon in children. Significant complications like cardiac dysfunction or hematologic malignancies can occur. Treatment has to be quickly started, in order to reduce eosinophilia. Haematological and echocardiographic follow-up are required.
Assuntos
Síndrome Hipereosinofílica/diagnóstico , Humanos , Síndrome Hipereosinofílica/tratamento farmacológico , Lactente , MasculinoRESUMO
Structural genomics (or proteomics) activities are critically dependent on the availability of high-throughput structure determination methodology. Development of such methodology has been a particular challenge for NMR based structure determination because of the demands for isotopic labeling of proteins and the requirements for very long data acquisition times. We present here a methodology that gains efficiency from a focus on determination of backbone structures of proteins as opposed to full structures with all sidechains in place. This focus is appropriate given the presumption that many protein structures in the future will be built using computational methods that start from representative fold family structures and replace as many as 70% of the sidechains in the course of structure determination. The methodology we present is based primarily on residual dipolar couplings (RDCs), readily accessible NMR observables that constrain the orientation of backbone fragments irrespective of separation in space. A new software tool is described for the assembly of backbone fragments under RDC constraints and an application to a structural genomics target is presented. The target is an 8.7 kDa protein from Pyrococcus furiosus, PF1061, that was previously not well annotated, and had a nearest structurally characterized neighbor with only 33% sequence identity. The structure produced shows structural similarity to this sequence homologue, but also shows similarity to other proteins, which suggests a functional role in sulfur transfer. Given the backbone structure and a possible functional link this should be an ideal target for development of modeling methods.
Assuntos
Genômica/métodos , Proteômica/métodos , Sequência de Aminoácidos , Marcação por Isótopo , Modelos Moleculares , Dados de Sequência Molecular , Conformação Proteica , Proteínas Recombinantes/química , SoftwareAssuntos
Antineoplásicos/uso terapêutico , Transplante de Medula Óssea/efeitos adversos , Leucemia-Linfoma de Células T do Adulto/terapia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Segunda Neoplasia Primária/tratamento farmacológico , Sarcoma/tratamento farmacológico , Talidomida/uso terapêutico , Pré-Escolar , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Sarcoma/patologia , Resultado do TratamentoRESUMO
Persistent polyclonal B-cell lymphocytosis (PPBL) is an intriguing disorder diagnosed predominantly in women, usually cigarette smokers, characterized by an increase in the number of polyclonal B lymphocytes. Abnormality of the B-cell population is also evidenced by the presence of multiple bcl-2/Ig gene rearrangements and the finding of an additional long arm chromosome 3q+ (i3)(q10) within a significant proportion of B cells. The physiopathology of PPBL is unknown but its association with the HLA DR7 phenotype suggests a possible genetic disorder. To further determine whether PPBL has a genetic predisposition, we have undertaken an extensive study in a large family of a patient diagnosed with PPBL. Three individuals among the first-degree relatives presented all the criteria for a diagnosis of PPBL. A slight increase in serum IgM without evidence of B-cell proliferation was shown in two additional siblings. Multiple bcl-2/Ig gene rearrangements, a typical feature of PPBL, were identified in 8/10 individuals among first-degree relatives. A statistically significant association was found between the presence of these rearrangements and of a paternal HLA haplotype. We conclude that PPBL has a familial occurrence suggesting an underlying genetic defect. The development of the complete syndrome probably relies on unidentified additional co-factors.