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The association of autoimmune cytopenia (AIC) and inflammatory bowel disease (IBD) has been reported in small series, but the incidence of and risk factors for IBD in children with AIC are not known. One thousand six hundred nine children with chronic immune thrombocytopenic purpura, autoimmune haemolytic anaemia or Evans syndrome from the prospective OBS'CEREVANCE cohort are included in this study. Overall, 15 children were diagnosed with IBD, including 14 who developed IBD after AIC diagnosis (median delay: 21 months). The only risk factor for IBD development is age at AIC over 10 years. Out of 10 children genetically tested, germline variants associated with autoimmune disorders were identified in three (CTLA4: two, DOCK11: one). In children and adolescents monitored for AIC or past history of AIC, especially children over 10 years, gastro-intestinal (GI) symptoms (recurrent abdominal pains, GI bleeding, chronic diarrhoea, weight loss) should suggest IBD and deserve specific work-up and genetic studies. Identification of a causal germline variant will allow targeted therapy.
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Abatacept/uso terapéutico , Anemia Hemolítica Autoinmune/tratamiento farmacológico , Antígeno CTLA-4/genética , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Trombocitopenia/tratamiento farmacológico , Adolescente , Adulto , Anemia Hemolítica Autoinmune/genética , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/genética , Niño , Preescolar , Femenino , Humanos , Masculino , Trombocitopenia/genética , Adulto JovenRESUMEN
The clinical and biological characteristics of children under 2 years (infants) with acute myeloid leukemia (AML) are different from those of older children. We aimed to describe the specific characteristics of this population and the potential factors that influence the prognosis. We analyzed data concerning 438 children with newly-diagnosed AML treated in the ELAM02 protocol between March 2005 and December 2011, of which 103 were under 2 years old at diagnosis. The evaluation criteria were overall survival (OS) and event-free survival (EFS) of infants vs older children. The clinical and biological features were secondary criteria. Infants presented more frequent extra-medullary presentation than older children. They had a significantly higher proportion of skin lesions and central nervous system involvement (15% vs 3%, pâ<â0.0001 and 26% vs 12%, pâ=â0.0005, respectively). The global incidence of KMT2A rearrangements was nearly 55% for infants vs 11% for older children (pâ<â0.0001). Median 5-year OS was 70.4% for infants vs 71.4% for older children (pâ=â0.83). Five-year EFS was 67% for infants vs 58% for older children (pâ=â0.27). Infants with AML represent a cohort of patients with specific clinical and biological features. These remarkable differences had no significant impact on their outcome in the ELAM02 protocol.
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BACKGROUND: Previous studies on the putative role of allergy in the aetiology of childhood leukaemia have reported contradictory results. The present study aimed to analyse the relation between a medical history of asthma or eczema and childhood acute lymphoid leukaemia (ALL) in light of potential candidate gene-environment interactions. METHODS: Analyses were based on a subset of 434 cases of ALL and 442 controls successfully genotyped and of European ancestry children enrolled in a French population-based case-control study conducted in 2003-2004. Information about medical history was obtained during a standardized interview with the mothers. Candidate polymorphisms in genes of the Th2 cytokines IL4, IL10, IL13 and IL4-receptor, were genotyped or imputed. RESULTS: None of the variant alleles were directly associated with childhood acute lymphoid leukaemia. A medical history of asthma or eczema was reported more often in the control group (ORâ¯=â¯0.7 [0.5-1.0]). This association was mostly seen in the group of children not carrying the IL13-rs20541 variant allele (Interaction Odds Ratio IOR 1.9, p-interactionâ¯=â¯0.07) and in those carrying the IL10 triple variant haplotype (IOR 0.5, p-interactionâ¯=â¯0.04). No interaction was observed with the candidate polymorphisms in IL4 and IL4R. CONCLUSION: This study provides a new insight into the relationship between allergic symptoms and childhood acute lymphoid leukaemia, by suggesting this inverse association could be limited to children carrying certain genetic polymorphisms. If confirmed, these results could help better understand the biological mechanisms involved in the development of childhood acute lymphoid leukaemia.
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Asma/genética , Eccema/genética , Interleucinas/genética , Polimorfismo de Nucleótido Simple , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Células Th2/metabolismo , Alelos , Asma/epidemiología , Estudios de Casos y Controles , Niño , Preescolar , Eccema/epidemiología , Femenino , Francia/epidemiología , Genotipo , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologíaRESUMEN
OBJECTIVES: Definitive diagnosis of invasive candidiasis (IC) may be difficult to achieve in patients with haematological malignancy (PHM). We aimed to evaluate the performance of BDG for the diagnosis and the follow-up of IC in PHM. PATIENTS AND METHODS: We retrospectively reviewed the serological data of BDG assay in adult and paediatric PHM, who developed candidemia or chronic disseminated candidiasis (CDC) through a 4-year period. Sensitivity and kinetics of BDG were determined for both clinical forms. RESULTS: In a panel of 3027 PHM, incidence rates of candidemia and CDC ranged between 0.74 and 0.77 and 0.30 and 0.44 according to the group of patients. At the time of diagnosis, 43.5% and 73% of cases of candidemia and CDC had a positive BDG assay, respectively. We found a significant correlation between the level of BDG at diagnosis and the outcome of candidemia (p = 0.022). In all cases of CDC, BDG negative results were obtained 2 to 6 months before recovery of the CT-scan lesions. CONCLUSIONS: BDG exhibits a low sensitivity to detect IC in PHM, but its kinetics correlates the clinical outcome. Additional studies are warranted in patients with CDC to evaluate the interest of monitoring BDG levels to anticipate the discontinuation of antifungal maintenance therapy.
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Candidemia/diagnóstico , Candidiasis Invasiva/diagnóstico , Candidiasis/diagnóstico , Neoplasias Hematológicas/microbiología , beta-Glucanos/sangre , Anciano , Anticuerpos Antifúngicos , Antifúngicos/uso terapéutico , Candida , Candidemia/tratamiento farmacológico , Candidiasis/tratamiento farmacológico , Candidiasis Invasiva/tratamiento farmacológico , Estudios de Seguimiento , Humanos , Unidades de Cuidados Intensivos , Cinética , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
Few studies are available on pediatricians' experience with announcing bad news. Announcing bad news is an important component of medical practice and is even more complex in pediatrics because parents must be associated. We had 20 hospital pediatricians complete a questionnaire containing 30 questions about their own experience announcing bad news to a child or a teenager. In spite of their experience and the time they have spent practicing medicine, there are many limitations stemming from different factors concerning children, teenagers, their families, and themselves. The difficulties encountered by pediatricians are mainly related to the timing of the announcement, the location, the choice of the words used, and the poor understanding of children and families, due to intellectual, cultural, or psychological limitations. Pediatricians question their own capacity to make such an announcement, wondering if the information has actually been well understood. They indicate that they are themselves affected. Most of them develop and implement strategies to refute the emotional instability caused by the announcement of bad news. Yet many of them feel weak, even talking about a deep sense of loneliness and guilt.
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Pediatras/psicología , Revelación de la Verdad , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , AutoinformeRESUMEN
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect often presenting with neonatal jaundice and/or hemolytic anemia. G6PD hemolytic events are linked with exposure to a pro-oxidant agent. We here report three cases of initial G6PD crises in breastfed children secondary to maternal consumption of a tonic drink which contains quinine. Quinine was found in breast milk of one of the mothers after she consumed tonic water. CONCLUSION: The amount of quinine that is transmitted through breast milk appears to be sufficient to induce G6PD crises in breastfed children. We hence recommend that consumption of quinine-containing sodas during breastfeeding should be avoided in populations with a high prevalence of G6PD deficiency. What is Known: ⢠G6PD hemolytic events are linked with exposure to a pro-oxidant agent. ⢠Ingestion of fava beans by a mother who was breastfeeding has been reported to induce a neonatal G6PD crisis. What is New: ⢠Maternal consumption of tonic drink which contains quinine appears to be sufficient to induce G6PD crises in breastfed children. ⢠Maternal consumption of quinine-containing sodas during breastfeeding should be avoided in populations with a high prevalence of G6PD deficiency.
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Lactancia Materna , Bebidas Gaseosas/toxicidad , Deficiencia de Glucosafosfato Deshidrogenasa/inducido químicamente , Oxidantes/toxicidad , Quinina/toxicidad , Femenino , Deficiencia de Glucosafosfato Deshidrogenasa/diagnóstico , Humanos , Lactante , Recién Nacido , MasculinoRESUMEN
BACKGROUND: Considering the remarkable efficacy of the strategies for preventing mother-to-child transmission of HIV infection (PMTCT), failures are rare in high-resource countries and deserve further investigation. Moreover, infants have been found to be at increased risk of viral failure. We analyzed the factors related to the children's environment, including maternal psychological factors that may be associated with viral failure in children diagnosed before the age of 1 year. PATIENTS AND METHODS: Retrospective study of all HIV-infected infants, born in France between July 2003 and July 2013, diagnosed before the age of 1 year, cared for in a single reference center, comparing the group of children in viral success to the group of children presenting at least one episode of viral failure, using data available in their medical, psychological and social files. RESULTS: Out of 1061 infants included in the prospective PMTCT follow-up, eight infants were found HIV-positive and an additional six cases were referred from other centers before the age of 1 year, for a total of 14 children born to 13 mothers. Seven children presented durable optimal viral control (VL<50 c/mL) whereas seven others did not reach or maintain optimal viral control over time. The main difference between the two groups was the presence among the mothers of children with viral failure of severe psychological disorders, leading to treatment adherence problems in the mothers who were aware of their HIV status before pregnancy, and difficulties in giving their children's treatments correctly. CONCLUSIONS: Although seroconversion during pregnancy is responsible for a significant proportion of residual transmission in high-resource countries, severe psychological or psychiatric conditions in HIV-positive mothers play an important role on the risk of both MTC residual transmission and viral failure in their infants.
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Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/prevención & control , Infecciones por VIH/transmisión , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Femenino , Estudios de Seguimiento , Infecciones por VIH/psicología , VIH-1/efectos de los fármacos , Humanos , Lactante , Recién Nacido , Masculino , Cumplimiento de la Medicación/psicología , Madres/psicología , Embarazo , Estudios Retrospectivos , Factores de Riesgo , Insuficiencia del TratamientoAsunto(s)
Leucemia Mieloide Aguda/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Calidad de Vida , Antineoplásicos/efectos adversos , Supervivientes de Cáncer , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Lactante , Recién Nacido , Leucemia Mieloide Aguda/terapia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapiaRESUMEN
Pediatric acute myeloid leukemia (AML) is a rare disease whose prognosis is highly variable according to factors such as chromosomal abnormalities. Recurrent genomic rearrangements are detected in half of pediatric AML by karyotype. NUcleoPorin 98 (NUP98) gene is rearranged with 31 different fusion partner genes. These rearrangements are frequently undetected by conventional cytogenetics, as the NUP98 gene is located at the end of the chromosome 11 short arm (11p15). By screening a series of 574 pediatric AML, we detected a NUP98 rearrangement in 22 cases (3.8%), a frequency similar to CBFB-MYH11 fusion gene (4.0%). The most frequent NUP98 fusion gene partner is NSD1. These cases are homogeneous regarding their biological and clinical characteristics, and associated with bad prognosis only improved by bone marrow transplantation. We detailed the biological characteristics of these AML by exome sequencing which demonstrated few recurrent mutations (FLT3 ITD, WT1, CEBPA, NBPF14, BCR and ODF1). The analysis of the clonal structure in these cases suggests that the mutation order in the NUP98-rearranged pediatric AML begins with the NUP98 rearrangement leading to epigenetic dysregulations then followed by mutations of critical hematopoietic transcription factors and finally, activation of the FLT3 signaling pathway.
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Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Proteínas de Complejo Poro Nuclear/genética , Translocación Genética , Alelos , Biomarcadores de Tumor , Proteínas Potenciadoras de Unión a CCAAT/genética , Niño , Preescolar , Epigénesis Genética , Exoma , Femenino , Regulación Leucémica de la Expresión Génica , Frecuencia de los Genes , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Hibridación Fluorescente in Situ , Lactante , Recién Nacido , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/mortalidad , Masculino , Mutación , Proteínas de Fusión Oncogénica/genética , Pronóstico , Transducción de Señal , Proteínas WT1/genética , Tirosina Quinasa 3 Similar a fms/metabolismoRESUMEN
Data on post-transplant iron overload (IO) are scarce in pediatrics. We conducted a prospective multicenter cohort study (Leucémie de l'Enfant et de l'Adolescent cohort) to determine the prevalence and risk factors of IO in 384 acute leukemia survivors transplanted during childhood. Prevalence of IO (ferritin level ⩾350 ng/mL) was 42.2% (95%CI 37.2-47.2%). Factors significantly associated with IO were: 1) in univariate analysis: older age at transplant (P<0.001), allogeneic versus autologous transplantation (P<0.001), radiation-based preparative regimen (P=0.035) and recent period of transplantation (P<0.001); 2) in multivariate analysis: older age at transplant in quartiles (Odds Ratio (OR)=7.64, 95% CI: 3.73-15.64 for age >12.7 years and OR=5.36, 95% CI: 2.63-10.95 for age from 8.2 to 12.7 years compared to age < 4.7 years), acute myeloid leukemia (OR=3.23, 95% CI: 1.47-7.13), allogeneic graft (OR=4.34, 95% CI: 2.07-9.12 for alternative donors and OR=2.53, 95% CI: 1.2-5.33 for siblings, compared to autologous graft) and radiation-based conditioning regimen (OR=2.45, 95% CI: 1.09-5.53). Graft-versus-host disease was an additional risk factor for allogeneic graft recipients. In conclusion, IO is a frequent complication in pediatric long-term survivors after transplantation for acute leukemia, more frequently observed in older children, those transplanted from alternative donors or with graft-versus-host disease.
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Supervivientes de Cáncer , Ferritinas/sangre , Trasplante de Células Madre Hematopoyéticas , Sobrecarga de Hierro/sangre , Sobrecarga de Hierro/epidemiología , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Acondicionamiento Pretrasplante , Factores de Edad , Aloinjertos , Niño , Femenino , Enfermedad Injerto contra Huésped/sangre , Enfermedad Injerto contra Huésped/epidemiología , Humanos , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/epidemiología , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Prevalencia , Factores de Riesgo , Donantes de TejidosRESUMEN
We analyzed the impact of cytogenetics on 193 children enrolled in two successive French trials (LAME89/91 and ELAM02), who received hematopoietic stem cell transplantation during CR1. Detailed karyotype was available for 66/74 (89%) in LAME89/91 and 118/119 (99%) in ELAM02. Several karyotype and transplant characteristics differed according to therapeutic protocol: unfavorable karyotypes were more frequent in ELAM02 (36% vs 18%), pretransplant chemotherapy included high-dose cytarabine in ELAM02 and not in LAME89/91, IV replaced oral busulfan in the conditioning regimen, methotrexate was removed from post-transplant immunosuppression, and matched unrelated donor and cord blood transplantation were introduced. Five-year overall survival (OS) was 78.2% in LAME89 and 81.4% in ELAM02. OS was significantly lower for the unfavorable cytogenetic risk group in LAME89/91 when compared with intermediate and favorable groups (50% vs 90.6 and 86.4%, P=0.001). This difference was no longer apparent in ELAM02 (80.9% vs 71.3% and 5/5, respectively). Survival improvement for children with unfavorable karyotype was statistically significant (P=0.026) and was due to decrease in relapse risk. Five-year transplantation-related mortality was 6.75% in LAME89/91. In ELAM02, it was 3.2% for patients with a sibling donor and 10.9% with an unrelated donor or cord blood. We conclude that the outcome of children with unfavorable karyotype transplanted in CR1 has improved.
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Citogenética , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Niño , Femenino , Francia , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Cariotipificación , Leucemia Mieloide Aguda/mortalidad , Masculino , Inducción de Remisión , Análisis de Supervivencia , Trasplante Homólogo , Resultado del TratamientoRESUMEN
INTRODUCTION: According to the European Society of Pediatric Oncology (SIOPE) standard of care guidelines, high-quality care of children and adolescents with cancer needs to be delivered by well-trained multidisciplinary teams in specialist centers working with designated shared-care local centers in a so-called hub-and-spoke model. The Diplôme Inter-Universitaire d'Oncologie Pédiatrique (DIUOP) is the only European training program in pediatric oncology in French for all physicians involved in care of patients with pediatric malignancies. In agreement with the SIOPE syllabus, the DIUOP is composed of training courses (120h), on-site practical training in a specialist center, and a research project to be defended before an examining board. METHOD: All graduates received a questionnaire to describe their current professional position. A comprehensive PubMed analysis retrieved all papers published form DIUOP research projects. RESULTS: From 2000 to 2011, 290 physicians were trained: 242 pediatricians, 21 surgeons, and 19 radiation therapists. Eight had another specialty including imaging, hematology, and pathology. Ninety-two were initially trained outside of France: 50% in Europe (mainly in Italy, Belgium, and Switzerland), 42% in Africa and the Middle East, and 8% in South America. Of the 266 graduates, 74% answered the questionnaire, and 90% of them take care of children and adolescents with cancer. Sixty-nine articles, i.e., one out of four research projects, were published in 34 journals with a median impact factor of 3.5 (0-22.6), 85% in English. CONCLUSION: DIUOP is the only French-speaking European education program providing a high-quality, professionalizing, and comprehensive multidisciplinary training program for French and international specialists taking care of children and adolescents with cancer.
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Hematología/educación , Oncología Médica/educación , Pediatría/educación , Adolescente , Niño , Francia , Humanos , Comunicación Interdisciplinaria , Neoplasias/terapia , Encuestas y CuestionariosRESUMEN
BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) syndrome is a childhood cancer predisposition syndrome involving biallelic germline mutations of MMR genes, poorly recognised by clinicians so far. METHODS: Retrospective review of all 31 patients with CMMRD diagnosed in French genetics laboratories in order to describe the characteristics, treatment and outcome of the malignancies and biological diagnostic data. RESULTS: 67 tumours were diagnosed in 31 patients, 25 (37%) Lynch syndrome-associated malignancies, 22 (33%) brain tumours, 17 (25%) haematological malignancies and 3 (5%) sarcomas. The median age of onset of the first tumour was 6.9â years (1.2-33.5). Overall, 22 patients died, 9 (41%) due to the primary tumour. Median survival after the diagnosis of the primary tumour was 27â months (0.26-213.2). Failure rate seemed to be higher than expected especially for T-cell non-Hodgkin's lymphoma (progression/relapse in 6/12 patients). A familial history of Lynch syndrome was identified in 6/23 families, and consanguinity in 9/23 families. PMS2 mutations (n=18) were more frequent than other mutations (MSH6 (n=6), MLH1 (n=4) and MSH2 (n=3)). CONCLUSIONS: In conclusion, this unselected series of patients confirms the extreme severity of this syndrome with a high mortality rate mostly related to multiple childhood cancers, and highlights the need for its early detection in order to adapt treatment and surveillance.
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Neoplasias Encefálicas/diagnóstico , Neoplasias Colorrectales/diagnóstico , Síndromes Neoplásicos Hereditarios/diagnóstico , Proteínas Adaptadoras Transductoras de Señales/genética , Adenosina Trifosfatasas/genética , Adolescente , Adulto , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Niño , Preescolar , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/terapia , Enzimas Reparadoras del ADN/genética , Proteínas de Unión al ADN/genética , Femenino , Humanos , Lactante , Masculino , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto , Homólogo 1 de la Proteína MutL , Proteína 2 Homóloga a MutS/genética , Mutación , Síndromes Neoplásicos Hereditarios/genética , Síndromes Neoplásicos Hereditarios/terapia , Proteínas Nucleares/genética , Resultado del Tratamiento , Adulto JovenRESUMEN
We evaluated prospectively the incidence and risk factors of the metabolic syndrome (MS) and its components in 170 adult patients (mean age at evaluation: 24.8±5.4 years) who received an hematopoietic stem cell transplantation for childhood ALL, n=119, or AML, n=51. TBI was carried out in 124 cases; a busulfan-based conditioning was done in 30 patients. Twenty-nine patients developed a MS (17.1%, 95% confidence intervals: 11.7-23.6). The cumulative incidence was 13.4% at 25 years of age and 35.5% at 35 years of age. A higher body mass index (BMI) before transplantation and a growth hormone deficiency were associated with increased MS risk (P=0.002 and 0.01, respectively). MS risk was similar for patients who received TBI or busulfan-based conditioning. The TBI use increased the hyperglycemia risk (odds ratio (OR): 4.7, P=0.02). Women were at the risk of developing increased waist circumference (OR: 7.18, P=0.003) and low levels of high-density lipoprotein cholesterol (OR: 2.72, P=0.007). The steroid dose was not a risk factor. The MS occurs frequently among transplanted survivors of childhood leukemia. Its incidence increases with age. Both intrinsic (BMI, gender) and extrinsic factors (TBI, alkylating agents) contribute to its etiopathogenesis.
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Trasplante de Células Madre Hematopoyéticas/efectos adversos , Síndrome Metabólico/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Sobrevivientes , Acondicionamiento Pretrasplante/efectos adversos , Corticoesteroides/administración & dosificación , Corticoesteroides/efectos adversos , Adulto , Antineoplásicos Alquilantes/efectos adversos , Antineoplásicos Alquilantes/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Glucemia/análisis , Índice de Masa Corporal , Busulfano/uso terapéutico , HDL-Colesterol/sangre , Terapia Combinada , Femenino , Humanos , Lípidos/sangre , Masculino , Síndrome Metabólico/sangre , Agonistas Mieloablativos/efectos adversos , Agonistas Mieloablativos/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Factores Sexuales , Circunferencia de la Cintura , Irradiación Corporal Total/efectos adversos , Adulto JovenRESUMEN
PURPOSE: To investigate the role of parental smoking during pre-conception and pregnancy, maternal beverage consumption (alcohol, coffee and tea) during pregnancy and their possible interactions, in the etiology of childhood acute leukemia (CL). METHODS: The ESTELLE study included 747 cases of CL [636 cases of acute lymphoblastic leukemia (ALL) and 100 cases of acute myeloblastic leukemia (AML)] diagnosed in France in 2010-2011 and 1,421 population controls frequency-matched with the cases on age and gender. Data were obtained from structured telephone questionnaires administered to the mothers. The odds ratios (OR) and their 95 % confidence intervals were estimated using unconditional logistic regression models adjusted for potential confounders. RESULTS: AML, but not ALL, was non-significantly associated with alcohol drinking during pregnancy [OR = 1.3 (0.8-2.0)] with a significant positive dose-response trend (p-trend = 0.02). Pre-conception paternal smoking was significantly associated with ALL [OR = 1.2 (1.1-1.5)] and AML [OR = 1.5 (1.0-2.3)]. CL was not associated with maternal smoking [OR = 1.0 (0.8-1.2)], or maternal coffee [OR = 0.9 (0.8-1.1)] or tea drinking [OR = 0.9 (0.8-1.1)] during pregnancy. However, a high consumption of coffee (>2 cups/day) was significantly associated with ALL [OR = 1.3 (1.0-1.8)]. CONCLUSIONS: The findings constitute additional evidence that maternal alcohol drinking during pregnancy may be involved in AML, and that paternal smoking before pregnancy may be a risk factor for CL. The role of maternal coffee drinking in CL remains unclear and should be investigated further in consortium analyses and in large birth cohort studies with exposure assessment more contemporaneous with the exposure, before the occurrence of the disease.
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Consumo de Bebidas Alcohólicas/epidemiología , Leucemia Mieloide Aguda/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Efectos Tardíos de la Exposición Prenatal , Fumar/epidemiología , Contaminación por Humo de Tabaco/efectos adversos , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Preescolar , Café , Femenino , Francia/epidemiología , Humanos , Lactante , Recién Nacido , Modelos Logísticos , Masculino , Oportunidad Relativa , Padres , Embarazo , Factores de Riesgo , Encuestas y Cuestionarios , TéRESUMEN
UNLABELLED: The most common diagnosis for pediatric thrombocytopenia is immune thrombocytopenia. Nevertheless, in atypical cases, the hypothesis of an inherited thrombocytopenia has to be investigated. We report a series of cases of a newly described entity, genetic thrombocytopenia with mutation in the ankyrine 26 gene, diagnosed from the exploration of five pediatric cases of thrombocytopenia. This entity is characterized by a moderate thrombocytopenia with normal mean platelet volume, and poorly bleeding. Its transmission is autosomal dominant. Final diagnosis is made by sequencing of a short DNA region of ANKRD26 gene. This pathology can be considered as an hematological malignancy predisposition syndrome. CONCLUSION: We report the first cohort of pediatric patients diagnosed with thrombocytopenia with mutation in the ankyrine 26. The aim is to underline the specificities of this entity in children and bring it to the knowledge of pediatricians who may be in first place to manage these patients. WHAT IS KNOWN: ⢠Genetic thrombocytopenia with mutation in the ankyrine 26 gene is a recently described entity, which seems to be considered as a predisposition for hematologic malignancies. ⢠The first cohort has been reported in 2011, by Noris et al., in 78 Italian adult patients. What is New: ⢠We describe clinical and biological features of the first pediatric cohort diagnosed with genetic thrombocytopenia with mutation in the ankyrine 26 gene. ⢠It seemed important to consider the pediatric specificities of this entity to enable pediatricians to investigate, diagnose, and manage pediatric patients and their families.
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ADN/genética , Mutación , Trombocitopenia/genética , Adolescente , Adulto , Repetición de Anquirina , Niño , Preescolar , Análisis Mutacional de ADN , Femenino , Predisposición Genética a la Enfermedad , Herencia , Humanos , Péptidos y Proteínas de Señalización Intercelular , Masculino , Persona de Mediana Edad , Proteínas Nucleares , Linaje , Trombocitopenia/diagnóstico , Trombocitopenia/metabolismoRESUMEN
We report French prospective experience with reduced-intensity conditioning-allo-SCT in 46 patients (median age: 15.5 years, 4.8-20.2) presenting high-risk AL (n=11), Hodgkin's lymphoma (n=15) or solid tumors (n=20). Graft sources were BM (n=21), PBSC (n=20) and cord blood (CB; n=5) from related (n=20) or unrelated (n=26) donors. For CB grafts, only one patient out of five achieved sustained engraftment. For PBSC/BM grafts, engraftment rate was 95%, hematopoietic recovery times were not significantly different between BM, PBSC, sibling or unrelated grafts, day+100. Full donor chimerism was achieved in 94% of patients, and incidences of primary acute GVHD and chronic GVHD were 49% and 14%, respectively. Underlying disease was fatal in 39% of patients. TRM was 6.9%. Three-year OS was 49.15%. OS and EFS were not significantly different between patients transplanted with different grafts and with or without primary GVHD. Patients with solid tumor or measurable disease at transplant had poorer outcomes. Three-year EFS: 33.3% for ALL, 75.0% for AML, 51.8% for Hodgkin's lymphoma, 28.6% for neuroblastoma and 22.2% for sarcoma patients. This multicentre study concluded that Bu/fludarabine/anti-thymocyte globulin conditioning with PB or BM, related or unrelated grafts in patients with various malignancies at high-risk for transplantation toxicity results in high engraftment rates, low TRM and acceptable survival.