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1.
Eur J Pediatr ; 179(1): 91-98, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31659466

RESUMO

The adequate nutritional status of pediatric cancer patients is particularly important to enable them to cope with the demands of the disease and its treatment and to maintain normal growth. Malnutrition and obesity have both been associated with reduced survival and increased drug toxicity. We investigated trends in the age- and sex-adjusted body mass index (ISO-BMI) and the prevalence of malnutrition in a Finnish cohort of 139 consecutive children receiving chemotherapy for cancer, with a follow-up period of 42 months after diagnosis. In total, 28% (39/139) of the patients experienced malnutrition (ISO-BMI < 17 or > 10% weight loss), and 12% (16/139) had a nasogastric tube or underwent gastrostomy. Patients with acute or chronic myeloid leukemia (5/10), central nervous system (CNS) tumors (5/13), or solid tumors (13/31) most frequently suffered from malnutrition. There was a significant increase in the ISO-BMI of patients with acute lymphoblastic leukemia (ALL) (+ 2.1 kg/m2) and lymphomas (+ 2.4 kg/m2) during the first 6 months, and the ISO-BMI of patients with ALL remained higher at 42 months compared to baseline (+ 1.9 kg/m2).Conclusion: The cumulative incidence of malnutrition in Finnish pediatric cancer patients is comparable to that reported in other populations. The nutritional status of patients with acute myeloid leukemia, CNS tumors, or solid tumors should be monitored with extra care to facilitate early intervention in the case of impending malnutrition.What is known:• Both malnutrition and obesity are associated with reduced survival and increased drug toxicity in pediatric cancer patients.What is new:• Overall, 28 % of Finnish children receiving chemotherapy for cancer suffer from malnutrition during the first 42 months following the initial cancer diagnosis. • ISO-BMI curves from initial diagnosis to 42 months after diagnosis are provided for patients with different types of cancer.


Assuntos
Índice de Massa Corporal , Desnutrição/etiologia , Neoplasias/complicações , Adolescente , Criança , Pré-Escolar , Feminino , Finlândia , Seguimentos , Humanos , Incidência , Masculino , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Prevalência , Estudos Retrospectivos , Fatores de Risco
2.
Blood ; 129(16): 2266-2279, 2017 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-28202457

RESUMO

Several monogenic causes of familial myelodysplastic syndrome (MDS) have recently been identified. We studied 2 families with cytopenia, predisposition to MDS with chromosome 7 aberrations, immunodeficiency, and progressive cerebellar dysfunction. Genetic studies uncovered heterozygous missense mutations in SAMD9L, a tumor suppressor gene located on chromosome arm 7q. Consistent with a gain-of-function effect, ectopic expression of the 2 identified SAMD9L mutants decreased cell proliferation relative to wild-type protein. Of the 10 individuals identified who were heterozygous for either SAMD9L mutation, 3 developed MDS upon loss of the mutated SAMD9L allele following intracellular infections associated with myeloid, B-, and natural killer (NK)-cell deficiency. Five other individuals, 3 with spontaneously resolved cytopenic episodes in infancy, harbored hematopoietic revertant mosaicism by uniparental disomy of 7q, with loss of the mutated allele or additional in cisSAMD9L truncating mutations. Examination of 1 individual indicated that somatic reversions were postnatally selected. Somatic mutations were tracked to CD34+ hematopoietic progenitor cell populations, being further enriched in B and NK cells. Stimulation of these cell types with interferon (IFN)-α or IFN-γ induced SAMD9L expression. Clinically, revertant mosaicism was associated with milder disease, yet neurological manifestations persisted in 3 individuals. Two carriers also harbored a rare, in trans germ line SAMD9L missense loss-of-function variant, potentially counteracting the SAMD9L mutation. Our results demonstrate that gain-of-function mutations in the tumor suppressor SAMD9L cause cytopenia, immunodeficiency, variable neurological presentation, and predisposition to MDS with -7/del(7q), whereas hematopoietic revertant mosaicism commonly ameliorated clinical manifestations. The findings suggest a role for SAMD9L in regulating IFN-driven, demand-adapted hematopoiesis.


Assuntos
Disfunção Cognitiva/diagnóstico , Síndromes de Imunodeficiência/diagnóstico , Mutação , Síndromes Mielodisplásicas/diagnóstico , Pancitopenia/diagnóstico , Proteínas Supressoras de Tumor/genética , Adulto , Alelos , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Linfócitos B/patologia , Proliferação de Células , Criança , Cromossomos Humanos Par 7/química , Disfunção Cognitiva/complicações , Disfunção Cognitiva/genética , Disfunção Cognitiva/imunologia , Feminino , Expressão Gênica , Hematopoese/imunologia , Heterozigoto , Humanos , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/imunologia , Imunofenotipagem , Interferon Tipo I/farmacologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Masculino , Pessoa de Meia-Idade , Mosaicismo , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/imunologia , Células Mieloides/efeitos dos fármacos , Células Mieloides/imunologia , Células Mieloides/patologia , Pancitopenia/complicações , Pancitopenia/genética , Pancitopenia/imunologia , Linhagem , Proteínas Supressoras de Tumor/metabolismo
3.
J Pediatr Hematol Oncol ; 40(1): e13-e18, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29200159

RESUMO

Posterior reversible encephalopathy syndrome (PRES) in children with acute lymphoblastic leukemia has been increasingly recognized as a clinicoradiological entity. Our aim was to describe the incidence of PRES in pediatric patients with ALL, identify its risk factors, and examine its prognostic importance. For this research, we conducted a systematic, retrospective review of the patient records in a population-based series of children with acute lymphoblastic leukemia (n=643) treated in Finland from 1992 to 2008. Of the patients with ALL, 4.5% (n=29) developed radiologically confirmed PRES, of which 28 cases occurred during induction. Hypertension (P=0.006; odds ratio [OR], 4.10, confidence interval [CI], 1.50-11.25), constipation (P=0.001; OR, 5.60; CI, 2.02-15.52), and >14 days of alkalinization (P=0.017; OR, 3.27; CI, 1.23-8.68) were significant independent risk factors for PRES. One-third of the patients developed epilepsy. Relapses occurred significantly more often in those patients with PRES (P=0.001), which was associated with worse overall survival (P=0.040; 5-year survival=75.9% [60.3%-91.4%] vs. 88.4% [85.8%-90.9%]). Using NOPHO-ALL 92/2000 protocols, PRES is a significant early complication of therapy in ALL, and was associated with a poorer prognosis and significant neurological morbidity.


Assuntos
Síndrome da Leucoencefalopatia Posterior/induzido quimicamente , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Adolescente , Criança , Pré-Escolar , Epilepsia/etiologia , Feminino , Finlândia/epidemiologia , Humanos , Hipertensão/etiologia , Incidência , Quimioterapia de Indução/efeitos adversos , Lactente , Masculino , Síndrome da Leucoencefalopatia Posterior/epidemiologia , Síndrome da Leucoencefalopatia Posterior/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Convulsões/etiologia , Análise de Sobrevida
4.
Psychooncology ; 25(6): 677-83, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26434559

RESUMO

BACKGROUND: Reports on the quality of life (QOL) of childhood brain tumor (BT) survivors have been inconsistent. As cognitive limitations may restrict their participation in questionnaire-based studies, our aim was to evaluate in depth the QOL with a mixed-method analysis. METHODS: The 5-year survivors of childhood BTs born in 1975-2000 and alive in 2010 were identified via the Finnish Cancer Registry and treating clinics. Twenty-one survivors (32%) participated in a mixed-method analysis including 15D (a general health-related QOL questionnaire), the Beck Depression Inventory, and a qualitative semi-structured interview. RESULTS: Based on the 15D-questionnaire, the BT survivors had an impaired health-related QOL in several dimensions such as speech and usual activities. On the other hand, no difference was found in other dimensions such as distress or vitality. A majority (95%) of the survivors showed no increased risk for depression. The qualitative interview revealed that the most important aspects affecting the QOL of the survivors were positive mental growth, negative conceptions concerning illness, living one day at a time, age at diagnosis, time since diagnosis, social relationships, learning disabilities and limitations in vocational opportunities, limitations in independent life, and changed understanding of the term 'health'. CONCLUSIONS: Childhood BT survivors have heterogeneous attitudes on QOL. The survivors assess social aspects to be more important than functionality for their QOL. Social concerns should actively be brought up to offer support for those with significant social difficulties. Interventions for social difficulties should be more actively developed. Copyright © 2015 John Wiley & Sons, Ltd.


Assuntos
Neoplasias Encefálicas/psicologia , Saúde Mental , Qualidade de Vida/psicologia , Sobreviventes/psicologia , Adulto , Neoplasias Encefálicas/terapia , Criança , Depressão/psicologia , Feminino , Humanos , Masculino , Prognóstico , Inquéritos e Questionários
6.
Duodecim ; 130(20): 2108-11, 2014.
Artigo em Finlandês | MEDLINE | ID: mdl-25558609

RESUMO

We describe three previously healthy children who developed acute extensive bruises about two weeks after a mild stomach bug. Coagulation tests revealed a shortened thromboplastin time (TT), long PT time, low level of coagulation factor II, and positive lupus anticoagulant among the antiphospholipid antibodies. In one patient the clinical symptoms disappeared during a one-week course of prednisolone, another one received a prothrombin complex preparation as substitution therapy. In the third patient the symptoms were milder and vanished without any specific treatment. The levels of coagulation factor increased in all patients and the lupus anticoagulant disappeared within a couple of months.


Assuntos
Anticorpos Antifosfolipídeos/sangue , Transtornos Hemorrágicos/sangue , Testes de Coagulação Sanguínea , Criança , Diagnóstico Diferencial , Glucocorticoides/uso terapêutico , Transtornos Hemorrágicos/tratamento farmacológico , Humanos , Prednisolona/uso terapêutico , Protrombina/uso terapêutico
7.
Duodecim ; 130(22-23): 2320-30, 2014.
Artigo em Finlandês | MEDLINE | ID: mdl-25558594

RESUMO

The number of long-term survivors after cancer therapy in childhood and young adulthood is increasing. Accordingly, life-long follow-up of significant health problems related to the given cancer therapy is needed as only one third of the survivors will remain free of any physical or psychosocial late effects. At present, national activity is needed to establish a uniform follow-up clinic service to support education, diagnostics, therapy and rehabilitation of these long-term adverse effects after cancer therapy at young age.


Assuntos
Continuidade da Assistência ao Paciente/organização & administração , Oncologia/organização & administração , Neoplasias/terapia , Sobreviventes , Adolescente , Adulto , Criança , Intervalo Livre de Doença , Humanos , Qualidade de Vida , Fatores de Risco
8.
Pediatr Blood Cancer ; 59(1): 197-8, 2012 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-22012661

RESUMO

The mobilization of stem cells using the standard approach, chemotherapy and G-CSF, may not be successful in all cases heavily pretreated. Plerixafor (AMD3100) has emerged as a viable option in attempts to mobilize stem cells among these patients. The use of plerixafor in the adult setting has been established, but data on pediatric use is scarce. We report on the use of plerixafor in eight pediatric cases either as add-on to chemotherapy plus G-CSF or in remobilization.


Assuntos
Separação Celular/instrumentação , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco de Sangue Periférico , Adolescente , Adulto , Separação Celular/métodos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Neoplasias/terapia , Transplante Autólogo
9.
J Pediatr Hematol Oncol ; 34(4): 263-70, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22246158

RESUMO

Despite improved treatment results of childhood acute lymphoblastic leukemia (ALL), 20% to 30% have a relapse, and then the outcome is very poor. We studied 40 children with ALL marrow relapse piloting an ALL relapse protocol with well-known drugs and drug combinations by using a concept of response-guided design. We also measured response in logarithmic fashion. Our primary end points were achievement of M1 marrow status, minimal residual disease status below 10, and second remission. The remission induction rate was 90% with 10% induction mortality. After the A blocks (dexamethasone, vincristine, idarubicin and pegylated L-asparaginase), 85% had M1 status, 39% had minimal residual disease ≤1×10, and 66% had 2 to 3 log response. After B1 block (cyclo, VP-16) the figures were 92%, 58%, and 83%, respectively. Twenty-five of 40 patients received allogeneic stem cell transplantation. Three-year event-free survival of the whole cohort was 37%, and the relapse rate was 38%. Three-year event-free survival by risk group was 53% for late, 34% for early, and 21% for very early relapses. An ALL marrow relapse nonresponsive to steroids, vincristine, asparaginase, anthracyclines, and alkylating agents is uncommon, and these classic drugs can still be advocated for induction of ALL relapse. The problems lie in creating a consolidation capable of preventing particularly posttransplant relapses.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Medula Óssea , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/prevenção & controle , Transplante de Células-Tronco , Adolescente , Ácido Aspártico/administração & dosagem , Criança , Pré-Escolar , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Idarubicina/administração & dosagem , Lactente , Masculino , Projetos Piloto , Recidiva , Indução de Remissão , Taxa de Sobrevida , Transplante Homólogo , Vincristina/administração & dosagem
10.
Br J Haematol ; 152(5): 623-30, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21241281

RESUMO

The frequency and causes of treatment-related deaths (TRD) in second complete remission (CR2) in acute myeloid leukaemia (AML) were investigated in a historical, prospective cohort study of 429 children included in the Nordic Society of Paediatric Haematology and Oncology (NOPHO)-AML-88 and -93 trials. Relapse occurred in 158 children (39%). Seventeen (18%) of the 96 patients entering CR2 suffered TRD. The main causes were infection (59%) and complications from graft-versus-host disease (22%). Fourteen (82%) of 17 TRDs occurred in children undergoing haematopoietic stem cell transplantations (HSCT). Optimal supportive care after HSCT is essential, and studies on risk factors for TRD are needed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Leucemia Mieloide Aguda/tratamento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Progressão da Doença , Métodos Epidemiológicos , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Lactente , Leucemia Mieloide Aguda/mortalidade , Masculino , Infecções Oportunistas/mortalidade , Recidiva , Indução de Remissão , Países Escandinavos e Nórdicos/epidemiologia
11.
Br J Haematol ; 151(5): 447-59, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20955398

RESUMO

Despite major improvements in the cure rate of childhood acute myeloid leukaemia (AML), 5-15% of patients still die from treatment-related complications. In a historical prospective cohort study, we analysed the frequency, clinical features and risk factors for early deaths (ED) and treatment-related deaths (TRD) in 525 children included in the Nordic Society of Paediatric Haematology and Oncology (NOPHO)-AML-84, -88 and -93 trials. Seventy patients (13%) died before starting treatment or from treatment-related complications. The death rate rose from 11% in NOPHO-AML-84 to 29% in -88, but then fell to 8% in -93. Sixteen patients (3%) died within the first 2 weeks, mainly from bleeding or leucostasis. Hyperleucocytosis, age <2 or ≥10 years were risk factors. After day 15, 10% of patients died from treatment-related complications with infection as the main cause of death. Risk factors were age <2 or ≥10 years and treatment according to the NOPHO-AML-88 protocol. The number of EDs and TRDs in AML is high. Therefore optimal antifungal prophylaxis is essential, and studies on the benefit of antibacterial prophylaxis and individual risk factors for ED and TRD are needed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Leucemia Mieloide Aguda/mortalidade , Adolescente , Distribuição por Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Métodos Epidemiológicos , Finlândia/epidemiologia , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/mortalidade , Humanos , Islândia/epidemiologia , Lactente , Leucemia Mieloide Aguda/tratamento farmacológico , Infecções Oportunistas/mortalidade , Países Escandinavos e Nórdicos/epidemiologia , Distribuição por Sexo , Fatores de Tempo
12.
Leuk Lymphoma ; 60(6): 1469-1475, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30632847

RESUMO

Acute lymphoblastic leukemia (ALL) is a rare disease in infants. Asparaginase is an essential part of the treatment, and there Acute is a need to evaluate the efficiency and safety of this drug in this age group. We evaluated the pharmacokinetics of intramuscularly administered native E. coli asparaginase (Asparaginase Medac®) and PEG-asparaginase (Oncaspar®) as well as hypersensitivity reactions during treatment in Interfant-06 ( www.clinicaltrials.gov : NCT01025804). All patients without hypersensitivity had sufficiently high enzyme activity levels during treatment with both preparations. Patients with hypersensitivity reactions during treatment, characterized by the presence of either or not of clinical symptoms and no measurable enzyme activity, received ineffective therapy. For optimization of the bad prognosis in infant ALL, therapeutic drug monitoring should be performed for identification of patients who should be switched to a different asparaginase preparation because of inactivation of the drug.


Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Asparaginase/efeitos adversos , Asparaginase/farmacocinética , Hipersensibilidade a Drogas/etiologia , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/farmacocinética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Antineoplásicos/uso terapêutico , Asparaginase/uso terapêutico , Hipersensibilidade a Drogas/diagnóstico , Monitoramento de Medicamentos , Feminino , Seguimentos , Humanos , Quimioterapia de Indução , Lactente , Recém-Nascido , Masculino , Polietilenoglicóis/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Resultado do Tratamento
13.
Blood Adv ; 3(18): 2722-2731, 2019 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-31519648

RESUMO

Pathogenic germline variants in ETV6 have been associated with familial predisposition to thrombocytopenia and hematological malignancies, predominantly childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In addition, overrepresentation of a high hyperdiploid subtype and older age at diagnosis have been reported among sporadic BCP-ALL cases with germline variants in ETV6 We studied a family with 2 second-degree relatives who developed childhood high hyperdiploid BCP-ALL at ages 8 and 12 years, respectively. A constitutional balanced reciprocal translocation t(12;14)(p13.2;q23.1) was discovered in both patients by routine karyotyping at diagnosis and, subsequently, in 7 healthy family members who had not experienced hematological malignancies. No carriers had thrombocytopenia. Whole-genome sequencing confirmed the translocation, resulting in 2 actively transcribed but nonfunctional fusion genes, causing heterozygous loss and consequently monoallelic expression of ETV6 Whole-genome sequencing analysis of the affected female subjects' leukemia excluded additional somatic aberrations in ETV6 and RTN1 as well as shared somatic variants in other genes. Expression studies, performed to confirm decreased expression of ETV6, were not conclusive. We suggest that germline aberrations resulting in monoallelic expression of ETV6 contribute to leukemia susceptibility, whereas more severe functional deficiency of ETV6 is required for developing THC5. To our knowledge, this report is the first of a constitutional translocation disrupting ETV6 causing predisposition to childhood ALL.


Assuntos
Predisposição Genética para Doença/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteínas Proto-Oncogênicas c-ets/genética , Proteínas Repressoras/genética , Criança , Feminino , Humanos , Masculino , Translocação Genética , Variante 6 da Proteína do Fator de Translocação ETS
14.
Pediatr Infect Dis J ; 27(11): 974-80, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18833026

RESUMO

BACKGROUND: Respiratory viruses occur frequently in the community and are a common cause of fever in children. Data on respiratory viral infections in children with cancer are limited. METHODS: A long-term, prospective, multicenter study was carried out in Finland searching for respiratory viruses in febrile children with leukemia. For this purpose, 138 febrile episodes in 51 children with leukemia were analyzed. Twelve types of respiratory viruses were searched for by viral culture, antigen detection, and polymerase chain reaction tests. RESULTS: Evidence of a respiratory viral infection was found in 61 of 138 febrile episodes (44%), accounting for an incidence of 0.8 (range, 0-2.4) per person year at risk during the treatment of leukemia. The most common viruses detected were rhinovirus (22%), respiratory syncytial virus (11%), human bocavirus (5%), and influenza A virus (4%). Dual viral infections were detected in 12 cases (9%). Half of the children had respiratory symptoms with cough being the most common symptom. Two children developed pneumonia. The mean duration of fever was 2.6 (SD 1.7) days in children with respiratory viral infection and 2.1 (SD 1.3) days in children without evidence of viral infection (P = 0.44). CONCLUSIONS: Respiratory viruses are found commonly during febrile episodes in children with leukemia. The detection of viruses permits the use of available antiviral agents, may explain a poor response to antimicrobial agents, and minimizes the proportion of febrile episodes without possible etiologic agents in children with leukemia.


Assuntos
Leucemia Mieloide Aguda/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Infecções Respiratórias/virologia , Viroses/virologia , Adolescente , Bocavirus/isolamento & purificação , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/complicações , Infecções Comunitárias Adquiridas/virologia , Infecção Hospitalar/complicações , Infecção Hospitalar/virologia , Feminino , Febre/etiologia , Humanos , Lactente , Vírus da Influenza A/isolamento & purificação , Leucemia Mieloide Aguda/virologia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/virologia , Vírus Sinciciais Respiratórios/isolamento & purificação , Infecções Respiratórias/complicações , Infecções Respiratórias/diagnóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rhinovirus/isolamento & purificação , Viroses/complicações , Viroses/diagnóstico
15.
Pediatr Blood Cancer ; 51(4): 535-9, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18523995

RESUMO

BACKGROUND: High-dose methotrexate (HD-MTX) is commonly used in treatment of pediatric leukemias and lymphomas. Transient deterioration in renal function is frequently noted during HD-MTX treatment, but possible long-term changes are less well known. In this study we aimed to study long-term renal prognosis after HD-MTX treatment, and to find possible underlying risk factors for reduced renal function. PROCEDURE: Medical records of pediatric cancer patients treated with HD-MTX were reviewed retrospectively after follow-up of 1-10 years. Renal function before and after chemotherapy was investigated in a total of 28 patients. Assessment of glomerular and tubular function was prospectively evaluated in each case. Glomerular function was evaluated by either (51)Cr-EDTA or (99m)Tc-DTPA clearance methods, and by urinary albumin excretion. Tubular function was assessed by measuring blood electrolyte levels and urinary alpha(1)- or beta(2)-microglobulin. RESULTS: A decrease in glomerular filtration rate (GFR) was statistically significant as follow-up time increased (P = 0.02). Age at the time of diagnosis and exposure to potentially nephrotoxic antibiotics during cancer treatment had no influence on GFR. However, albuminuria was observed more often in patients treated with amphotericin B or gentamycin (P = 0.04). No changes in tubular function were observed. CONCLUSIONS: Our results show that HD-MTX treatment significantly decreases GFR and may cause albuminuria in pediatric cancer patients several years after treatment. Long-term renal follow-up of these patients is therefore important.


Assuntos
Rim/efeitos dos fármacos , Rim/fisiologia , Metotrexato/uso terapêutico , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Lactente , Masculino , Metotrexato/efeitos adversos , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Fatores de Tempo
16.
J Pediatr Hematol Oncol ; 30(11): 798-802, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18989155

RESUMO

PURPOSE: The purpose of this study was to find out the incidence of and clinical risk factors for magnetic resonance imaging (MRI)-detected osteonecrosis (ON) in children treated for lymphoma or solid tumors. PATIENTS AND METHODS: The development of ON was studied in 32 childhood cancer patients who underwent MRI scanning of the lower extremities at the end of their treatment. The underlying malignancy was Wilms tumor in 8 patients, non-Hodgkin lymphoma (NHL) in 8, Hodgkin disease (HD) in 7, rhabdomyosarcoma in 6, and other occasional solid tumors in 3 patients. RESULTS: Six of the 32 patients (19%) had ON. The mean age of the patients with ON at diagnosis was 12.7 years compared with 5.8 years for the patients without ON (P<0.001). All the patients with ON had either HD (4 patients) or NHL (2 patients). Two (33%) of the patients with ON were symptomatic. CONCLUSIONS: ON in MRI was found to be a common complication in children after treatment for HD or NHL. The risk for ON seems to be very low in patients with other solid tumors even when they receive high cumulative doses of dexamethasone.


Assuntos
Doença de Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Neoplasias/tratamento farmacológico , Osteonecrose/induzido quimicamente , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Pré-Escolar , Dexametasona/uso terapêutico , Feminino , Doença de Hodgkin/patologia , Humanos , Incidência , Linfoma não Hodgkin/patologia , Imageamento por Ressonância Magnética , Masculino , Neoplasias/patologia , Osteonecrose/diagnóstico , Fatores de Risco
17.
Eur J Pediatr ; 167(9): 1011-5, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18038236

RESUMO

A new human parvovirus, human bocavirus, has recently been identified in respiratory secretions, feces and serum. It is associated with lower and most likely also upper respiratory tract infections. Most commonly reported symptoms are cough, rhinorrhea, expiratory wheezing and fever, and the virus is preferentially detected in young children. We report three children with acute lymphoblastic leukemia who had acute febrile episodes with concomitant detection of human bocavirus in their respiratory secretions. One of them had five consecutive febrile episodes during 6 months, all associated with the presence of human bocavirus at varying viral loads, suggesting prolonged shedding or reactivation of the virus.


Assuntos
Bocavirus/isolamento & purificação , Infecções por Parvoviridae/complicações , Infecções por Parvoviridae/fisiopatologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Adolescente , Bocavirus/patogenicidade , Criança , Pré-Escolar , Finlândia , Humanos , Masculino , Mucosa Nasal/virologia
18.
Pediatr Infect Dis J ; 26(12): 1133-6, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18043451

RESUMO

BACKGROUND: Febrile infections in children with leukemia are common. The occurrence of possible mixed bacterial-viral infections is unknown. METHODS: We searched for viruses in leukemic children with blood culture-positive bacterial infections. The prospective multicenter survey included 156 febrile episodes in 51 children with acute leukemia. The mean follow-up time was 1.5 years per patient (27,743 patient-days at risk). Sixteen viruses were searched for from nasal swab and stool samples using virus culture, virus antigen detection, and polymerase chain reaction tests. RESULTS: Bacterial blood cultures were positive in 19 (11%) febrile episodes among 17 children. In half of the septic episodes (11 of 19), a virus was also found. Rhinovirus and respiratory syncytial virus were the most common viruses detected. CONCLUSIONS: Our findings suggest that invasive bacterial infections are commonly associated with viral infections in children with leukemia.


Assuntos
Bacteriemia/complicações , Leucemia/complicações , Viroses/complicações , Adolescente , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Infecções Bacterianas/complicações , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Sangue/microbiologia , Criança , Pré-Escolar , Fezes/virologia , Febre/etiologia , Humanos , Incidência , Lactente , Leucemia/epidemiologia , Cavidade Nasal/virologia , Vírus Sincicial Respiratório Humano/classificação , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/isolamento & purificação , Rhinovirus/classificação , Rhinovirus/genética , Rhinovirus/isolamento & purificação , Viroses/epidemiologia , Viroses/virologia , Vírus/classificação , Vírus/genética , Vírus/isolamento & purificação
20.
Genome Med ; 7: 130, 2015 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-26684649

RESUMO

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rapid-onset, potentially fatal hyperinflammatory syndrome. A prompt molecular diagnosis is crucial for appropriate clinical management. Here, we validated and prospectively evaluated a targeted high-throughput sequencing approach for HLH diagnostics. METHODS: A high-throughput sequencing strategy of 12 genes linked to HLH was validated in 13 patients with previously identified HLH-associated mutations and prospectively evaluated in 58 HLH patients. Moreover, 2504 healthy individuals from the 1000 Genomes project were analyzed in silico for variants in the same genes. RESULTS: Analyses revealed a mutation detection sensitivity of 97.3%, an average coverage per gene of 98.0%, and adequate coverage over 98.6% of sites previously reported as mutated in these genes. In the prospective cohort, we achieved a diagnosis in 22 out of 58 patients (38%). Genetically undiagnosed HLH patients had a later age at onset and manifested higher frequencies of known secondary HLH triggers. Rare, putatively pathogenic monoallelic variants were identified in nine patients. However, such monoallelic variants were not enriched compared with healthy individuals. CONCLUSIONS: We have established a comprehensive high-throughput platform for genetic screening of patients with HLH. Almost all cases with reduced natural killer cell function received a diagnosis, but the majority of the prospective cases remain genetically unexplained, highlighting genetic heterogeneity and environmental impact within HLH. Moreover, in silico analyses of the genetic variation affecting HLH-related genes in the general population suggest caution with respect to interpreting causality between monoallelic mutations and HLH. A complete understanding of the genetic susceptibility to HLH thus requires further in-depth investigations, including genome sequencing and detailed immunological characterization.


Assuntos
Sequência de Bases , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/genética , Adolescente , Adulto , Idade de Início , Idoso , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Testes Genéticos , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mutação , Estudos Prospectivos , Análise de Sequência de DNA , Adulto Jovem
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