RESUMEN
Central nervous system (CNS) involvement at diagnosis of pediatric acute myeloid leukemia (AML) is not considered as an independent prognostic factor. This study describes the prognostic value of pediatric AML with CNS involvement at diagnosis. Pediatric patients were treated for de novo AML in the French multicenter trial ELAM02. Lumbar puncture was carried out in the first week, and the treatment was adapted to the CNS status. No patient received CNS radiotherapy. The patients were classified into 2 groups: CNS+ and CNS-. Of the 438 patients, 16% (n=70) had CNS involvement at diagnosis, and 29% showed clinical signs. The patients with CNS disease were younger (40% were below 2 y old), had a higher white blood cell count (median of 45 vs. 13 G/L), and had M4 and M5 morphologies. The complete remission rate was similar at 92.8% for CNS+ and 88.5% for CNS-. There was no significant difference between the CNS+ and the CNS- group in overall survival (76% and 71%, respectively) and event-free survival (57% and 52%, respectively). Regarding the occurrence of first relapse, the CNS+ group had a higher combined relapse rate of 26.1% compared with 10% for the CNS- group. The results indicate that CNS involvement at diagnosis of pediatric AML is not an independent prognostic factor. Triple intrathecal chemotherapy combined with high-dose intravenous cytarabine should be the first-line treatment for CNS disease.
Asunto(s)
Neoplasias del Sistema Nervioso Central/diagnóstico , Leucemia Mieloide Aguda/diagnóstico , Pronóstico , Adolescente , Factores de Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios de Casos y Controles , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/mortalidad , Niño , Preescolar , Citarabina/administración & dosificación , Francia , Humanos , Lactante , Leucemia Monocítica Aguda , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/mortalidad , Leucemia Mielomonocítica Aguda , Recuento de Leucocitos , Recurrencia , Análisis de SupervivenciaRESUMEN
Comprehensive clinical studies of patients with acute megakaryoblastic leukemia (AMKL) are lacking. We performed an international retrospective study on 490 patients (age ≤18 years) with non-Down syndrome de novo AMKL diagnosed from 1989 to 2009. Patients with AMKL (median age 1.53 years) comprised 7.8% of pediatric AML. Five-year event-free (EFS) and overall survival (OS) were 43.7% ± 2.7% and 49.0% ± 2.7%, respectively. Patients diagnosed in 2000 to 2009 were treated with higher cytarabine doses and had better EFS (P = .037) and OS (P = .003) than those diagnosed in 1989 to 1999. Transplantation in first remission did not improve survival. Cytogenetic data were available for 372 (75.9%) patients: hypodiploid (n = 18, 4.8%), normal karyotype (n = 49, 13.2%), pseudodiploid (n = 119, 32.0%), 47 to 50 chromosomes (n = 142, 38.2%), and >50 chromosomes (n = 44, 11.8%). Chromosome gain occurred in 195 of 372 (52.4%) patients: +21 (n = 106, 28.5%), +19 (n = 93, 25.0%), +8 (n = 77, 20.7%). Losses occurred in 65 patients (17.5%): -7 (n = 13, 3.5%). Common structural chromosomal aberrations were t(1;22)(p13;q13) (n = 51, 13.7%) and 11q23 rearrangements (n = 38, 10.2%); t(9;11)(p22;q23) occurred in 21 patients. On the basis of frequency and prognosis, AMKL can be classified to 3 risk groups: good risk-7p abnormalities; poor risk-normal karyotypes, -7, 9p abnormalities including t(9;11)(p22;q23)/MLL-MLLT3, -13/13q-, and -15; and intermediate risk-others including t(1;22)(p13;q13)/OTT-MAL (RBM15-MKL1) and 11q23/MLL except t(9;11). Risk-based innovative therapy is needed to improve patient outcomes.
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Aberraciones Cromosómicas , Leucemia Megacarioblástica Aguda/genética , Leucemia Megacarioblástica Aguda/terapia , Adolescente , Antimetabolitos Antineoplásicos/uso terapéutico , Niño , Preescolar , Citarabina/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Reordenamiento Génico , Trasplante de Células Madre Hematopoyéticas , Humanos , Lactante , Estimación de Kaplan-Meier , Cariotipificación , Leucemia Megacarioblástica Aguda/diagnóstico , Leucemia Megacarioblástica Aguda/epidemiología , Masculino , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
In pediatric acute myeloid leukemia (AML), cytogenetic abnormalities are strong indicators of prognosis. Some recurrent cytogenetic abnormalities, such as t(8;16)(p11;p13), are so rare that collaborative studies are required to define their prognostic impact. We collected the clinical characteristics, morphology, and immunophenotypes of 62 pediatric AML patients with t(8;16)(p11;p13) from 18 countries participating in the International Berlin-Frankfurt-Münster (I-BFM) AML study group. We used the AML-BFM cohort diagnosed from 1995-2005 (n = 543) as a reference cohort. Median age of the pediatric t(8;16)(p11;p13) AML patients was significantly lower (1.2 years). The majority (97%) had M4-M5 French-American-British type, significantly different from the reference cohort. Erythrophagocytosis (70%), leukemia cutis (58%), and disseminated intravascular coagulation (39%) occurred frequently. Strikingly, spontaneous remissions occurred in 7 neonates with t(8;16)(p11;p13), of whom 3 remain in continuous remission. The 5-year overall survival of patients diagnosed after 1993 was 59%, similar to the reference cohort (P = .14). Gene expression profiles of t(8;16)(p11;p13) pediatric AML cases clustered close to, but distinct from, MLL-rearranged AML. Highly expressed genes included HOXA11, HOXA10, RET, PERP, and GGA2. In conclusion, pediatric t(8;16)(p11;p13) AML is a rare entity defined by a unique gene expression signature and distinct clinical features in whom spontaneous remissions occur in a subset of neonatal cases.
Asunto(s)
Cromosomas Humanos Par 16 , Cromosomas Humanos Par 8 , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidad , Translocación Genética/genética , Adolescente , Niño , Preescolar , Conducta Cooperativa , Femenino , Regulación Leucémica de la Expresión Génica , Alemania/epidemiología , Humanos , Lactante , Recién Nacido , Leucemia Mieloide Aguda/terapia , Masculino , Pronóstico , Remisión Espontánea , TranscriptomaRESUMEN
A minority of children with chronic immune thrombocytopenia (ITP) require therapeutic intervention to prevent haemorrhagic risk. This retrospective national study evaluated romiplostim in childhood non-responsive or refractory chronic ITP. Between 2009 and 2012, 10 patients whose Buchanan score was 3-4 were treated with romiplostim. The median duration of thrombocytopenia was 1·9 years (0·8-15). The median duration of romiplostim treatment was 9 months (3-36). A response was observed in 5/10 patients (one complete, four partial). No serious adverse effect was noticed. The long-term benefit/risk balance of this innovative treatment is currently recorded by Centre de Référence National des Cytopénies Auto-immunes de l'Enfant.
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Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Receptores Fc/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Trombopoyetina/uso terapéutico , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Francia , Humanos , Lactante , Masculino , Receptores Fc/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/efectos adversos , Estudios Retrospectivos , Trombopoyetina/administración & dosificación , Trombopoyetina/efectos adversos , Resultado del TratamientoRESUMEN
Acute myeloid leukemia with t(6;9)(p22;q34) is listed as a distinct entity in the 2008 World Health Organization classification, but little is known about the clinical implications of t(6;9)-positive myeloid leukemia in children. This international multicenter study presents the clinical and genetic characteristics of 62 pediatric patients with t(6;9)/DEK-NUP214-rearranged myeloid leukemia; 54 diagnosed as having acute myeloid leukemia, representing <1% of all childhood acute myeloid leukemia, and eight as having myelodysplastic syndrome. The t(6;9)/DEK-NUP214 was associated with relatively late onset (median age 10.4 years), male predominance (sex ratio 1.7), French-American-British M2 classification (54%), myelodysplasia (100%), and FLT3-ITD (42%). Outcome was substantially better than previously reported with a 5-year event-free survival of 32%, 5-year overall survival of 53%, and a 5-year cumulative incidence of relapse of 57%. Hematopoietic stem cell transplantation in first complete remission improved the 5-year event-free survival compared with chemotherapy alone (68% versus 18%; P<0.01) but not the overall survival (68% versus 54%; P=0.48). The presence of FLT3-ITD had a non-significant negative effect on 5-year overall survival compared with non-mutated cases (22% versus 62%; P=0.13). Gene expression profiling showed a unique signature characterized by significantly higher expression of EYA3, SESN1, PRDM2/RIZ, and HIST2H4 genes. In conclusion, t(6;9)/DEK-NUP214 represents a unique subtype of acute myeloid leukemia with a high risk of relapse, high frequency of FLT3-ITD, and a specific gene expression signature.
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Proteínas Cromosómicas no Histona/genética , Cromosomas Humanos Par 6 , Cromosomas Humanos Par 9 , Leucemia Mieloide/genética , Proteínas de Complejo Poro Nuclear/genética , Proteínas de Fusión Oncogénica/genética , Proteínas Oncogénicas/genética , Translocación Genética , Adolescente , Médula Ósea/patología , Niño , Preescolar , Femenino , Perfilación de la Expresión Génica , Trasplante de Células Madre Hematopoyéticas , Humanos , Lactante , Recién Nacido , Leucemia Mieloide/diagnóstico , Leucemia Mieloide/mortalidad , Leucemia Mieloide/terapia , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Masculino , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/terapia , Proteínas de Unión a Poli-ADP-Ribosa , Recurrencia , Resultado del TratamientoRESUMEN
BACKGROUND: Apheresis is a major challenge in peripheral stem cell collection from low-weight children with cancer. Comparisons between the new apheresis device Optia (TerumoBCT) and the earlier COBE Spectra (CaridianBCT) have been performed in adults but not in low-weight children. The objective was to compare the performance of these two devices in small children. STUDY DESIGN AND METHODS: In this retrospective study, all patients were reviewed weighing less than 15 kg undergoing stem cell collection using the Optia device between April 2011 and April 2012. They were paired on weight in a 3:1 ratio with patients whose cells had been collected with the COBE Spectra since 2006. RESULTS: Six patients were treated with the Optia and were matched with 18 patients treated with the Spectra. No side effects occurred. Collection efficiency (CE) was similar between the two groups (50% vs. 47%), but CD34 cell blood clearance was lower with the Optia (0.4 mL/min/kg vs. 0.6 mL/min/kg, p < 0.01). Platelet (PLT) loss and hemoglobin (Hb) loss were significantly reduced with the Optia (respectively, 32% vs. 54%, p < 0.01; and 1.4 g/dL vs. 2.9 g/dL, p < 0.01). Apheresis duration was increased with the Optia (159 min vs. 134 min, p < 0.05). The cell product harvested with the Optia had a lower volume and lower hematocrit, but similar white blood cell and PLT content. CONCLUSION: Compared with the Spectra, the Optia allows similar CE with a reduced PLT and Hb loss but with a longer duration.
Asunto(s)
Eliminación de Componentes Sanguíneos/instrumentación , Células Madre Hematopoyéticas/citología , Antígenos CD34/análisis , Peso Corporal , Niño , Preescolar , Femenino , Hemoglobinas/análisis , Humanos , Lactante , Masculino , Recuento de Plaquetas , Estudios RetrospectivosRESUMEN
We previously demonstrated that outcome of pediatric 11q23/MLL-rearranged AML depends on the translocation partner (TP). In this multicenter international study on 733 children with 11q23/MLL-rearranged AML, we further analyzed which additional cytogenetic aberrations (ACA) had prognostic significance. ACAs occurred in 344 (47%) of 733 and were associated with unfavorable outcome (5-year overall survival [OS] 47% vs 62%, P < .001). Trisomy 8, the most frequent specific ACA (n = 130/344, 38%), independently predicted favorable outcome within the ACAs group (OS 61% vs 39%, P = .003; Cox model for OS hazard ratio (HR) 0.54, P = .03), on the basis of reduced relapse rate (26% vs 49%, P < .001). Trisomy 19 (n = 37/344, 11%) independently predicted poor prognosis in ACAs cases, which was partly caused by refractory disease (remission rate 74% vs 89%, P = .04; OS 24% vs 50%, P < .001; HR 1.77, P = .01). Structural ACAs had independent adverse prognostic value for event-free survival (HR 1.36, P = .01). Complex karyotype, defined as ≥ 3 abnormalities, was present in 26% (n = 192/733) and showed worse outcome than those without complex karyotype (OS 45% vs 59%, P = .003) in univariate analysis only. In conclusion, like TP, specific ACAs have independent prognostic significance in pediatric 11q23/MLL-rearranged AML, and the mechanism underlying these prognostic differences should be studied.
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Aberraciones Cromosómicas , Cromosomas Humanos Par 11 , Reordenamiento Génico , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Proteína de la Leucemia Mieloide-Linfoide/genética , Niño , Preescolar , Cromosomas Humanos Par 19 , Cromosomas Humanos Par 8 , Estudios de Cohortes , Análisis Citogenético , Femenino , Estudios de Asociación Genética , N-Metiltransferasa de Histona-Lisina , Humanos , Lactante , Masculino , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Translocación Genética , TrisomíaRESUMEN
OBJECTIVES: Invasive fungal disease (IFD) remains a major concern in patients with haematological conditions. We describe diagnoses, therapeutic management and outcomes in unselected consecutive patients from haematological facilities treated for suspected or documented IFD. METHODS: In this observational prospective study, children/adults with haematological conditions or haematopoietic stem cell transplantation (HSCT) were recruited upon start of non-prophylactic systemic antifungal treatment in 37 French haematological facilities (December 2007 to December 2008). IFD episodes were classified according to the 2008 EORTC/MSG criteria. RESULTS: The cohort included 419 patients (298 adults and 121 children): 88% haematological malignancies, 28% HSCT recipients and 68% neutropenic. Patients had 423 IFD episodes: 21% mycologically documented (59% probable/proven aspergillosis, 32% proven candidiasis and 9% probable/proven other IFD) and 20% classified as possible IFD. The remaining cases were assigned to two groups: febrile neutropenia (34%) and unclassified (25%), 9% of which were classified as possible/probable/proven IFD by day 7. Treatment was thus initiated early in 59% of patients; liposomal amphotericin B and caspofungin were the most common single-agent therapies. The 12 week mortality was 18% for probable/proven aspergillosis, 15% for proven candidiasis, 10% for probable/proven other IFD, 9% for possible IFD, 3% for febrile neutropenia and 12% for unclassified episodes (log rank Pâ=â0.016); it was dependent on age, complete remission of underlying haematological disease and mechanical ventilation. CONCLUSIONS: In this comprehensive sample of haematological patients receiving antifungal treatment, we observe a widespread resort to early therapy and a low mortality rate, including in patients with probable or proven IFD.
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Antifúngicos/administración & dosificación , Neoplasias Hematológicas/complicaciones , Huésped Inmunocomprometido , Micosis/tratamiento farmacológico , Trasplante de Células Madre/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Francia , Humanos , Lactante , Masculino , Persona de Mediana Edad , Micosis/mortalidad , Estudios Prospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
Testing for SARS-CoV-2 is central to COVID-19 management. Rapid antigen test from self-collected anterior nasal swabs (SCANS-RAT) are often used in children but their performance have not been assessed in real-life. We aimed to compare this testing method to the two methods usually used: reverse transcription polymerase chain reaction from nasopharyngeal swabs collected by healthcare workers (HCW-PCR) and rapid antigen test from nasopharyngeal swabs collected by healthcare workers (HCW-RAT), estimating the accuracy and acceptance, in a pediatric real-life study. From September 2021 to January 2022, we performed a manufacturer-independent cross-sectional, prospective, multicenter study involving 74 pediatric ambulatory centers and 5 emergency units throughout France. Children ≥6 months to 15 years old with suggestive symptoms of COVID-19 or children in contact with a COVID-19-positive patient were prospectively enrolled. We included 836 children (median 4 years), 774 (92.6%) were symptomatic. The comparators were HCW-PCR for 267 children, and HCW-RAT for 593 children. The sensitivity of the SCANS-RAT test compared to HCW-RAT was 91.3% (95%CI 82.8; 96.4). Sensitivity was 70.4% (95%CI 59.2; 80.0) compared to all HCW-PCR and 84.6% (95%CI 71.9; 93.1) when considering cycle threshold <33. The specificity was always >97%. Among children aged ≥6 years, 90.9% of SCANS-RAT were self-collected without adult intervention. On appreciation rating (from 1, very pleasant, to 10, very unpleasant), 77.9% of children chose a score ≤3. SCANS-RAT have good sensitivity and specificity and are well accepted by children. A repeated screening strategy using these tests can play a major role in controlling the pandemic.
RESUMEN
Importance: An association between pneumococcal nasopharyngeal carriage and invasive pneumococcal disease (IPD) has been previously established. However, it is unclear whether the decrease in IPD incidence observed after implementation of nonpharmaceutical interventions (NPIs) during the COVID-19 pandemic was associated with concomitant changes in pneumococcal carriage and respiratory viral infections. Objective: To assess changes in IPD incidence after the implementation of NPIs during the COVID-19 pandemic and examine their temporal association with changes in pneumococcal carriage rate and respiratory viral infections (specifically respiratory syncytial virus [RSV] and influenza cases) among children in France. Design, Setting, and Participants: This cohort study used interrupted time series analysis of data from ambulatory and hospital-based national continuous surveillance systems of pneumococcal carriage, RSV and influenza-related diseases, and IPD between January 1, 2007, and March 31, 2021. Participants included 11 944 children younger than 15 years in France. Exposures: Implementation of NPIs during the COVID-19 pandemic. Main Outcomes and Measures: The estimated fraction of IPD change after implementation of NPIs and the association of this change with concomitant changes in pneumococcal carriage rate and RSV and influenza cases among children younger than 15 years. The estimated fraction of change was analyzed using a quasi-Poisson regression model. Results: During the study period, 5113 children (median [IQR] age, 1.0 [0.6-4.0] years; 2959 boys [57.9%]) had IPD, and 6831 healthy children (median [IQR] age, 1.5 [0.9-3.9] years; 3534 boys [51.7%]) received a swab test. Data on race and ethnicity were not collected. After NPI implementation, IPD incidence decreased by 63% (95% CI, -82% to -43%; P < .001) and was similar for non-13-valent pneumococcal conjugate vaccine serotypes with both high disease potential (-63%; 95% CI, -77% to -48%; P < .001) and low disease potential (-53%; 95% CI, -70% to -35%; P < .001). The overall pneumococcal carriage rate did not significantly change after NPI implementation (-12%; 95% CI, -37% to 12%; P = .32), nor did the carriage rate for non-PCV13 serotypes with high disease potential (-26%; 95% CI, -100% to 52%; P = .50) or low disease potential (-7%; 95% CI, -34% to 20%; P = .61). After NPI implementation, the estimated number of influenza cases decreased by 91% (95% CI, -74% to -97%; P < .001), and the estimated number of RSV cases decreased by 74% (95% CI, -55% to -85%; P < .001). Overall, the decrease in influenza and RSV cases accounted for 53% (95% CI, -28% to -78%; P < .001) and 40% (95% CI, -15% to -65%; P = .002) of the decrease in IPD incidence during the NPI period, respectively. The decrease in IPD incidence was not associated with pneumococcal carriage, with carriage accounting for only 4% (95% CI, -7% to 15%; P = .49) of the decrease. Conclusions and Relevance: In this cohort study of data from multiple national continuous surveillance systems, a decrease in pediatric IPD incidence occurred after the implementation of NPIs in France; this decrease was associated with a decrease in viral infection cases rather than pneumococcal carriage rate. The association between pneumococcal carriage and IPD was potentially modified by changes in the number of RSV and influenza cases, suggesting that interventions targeting respiratory viruses, such as immunoprophylaxis or vaccines for RSV and influenza, may be able to prevent a large proportion of pediatric IPD cases.
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COVID-19 , Vacunas contra la Influenza , Gripe Humana , Infecciones Neumocócicas , Virus , COVID-19/epidemiología , Niño , Estudios de Cohortes , Humanos , Lactante , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Masculino , Pandemias , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Streptococcus pneumoniaeRESUMEN
In unrelated hematopoietic stem cell transplantation (HSCT), the prediction of donor search outcome at the time of search initiation is of great value for the physicians to delineate the strategy of patient care. The probability of finding an unrelated donor is high for patients who carry at least 1 of the 10 most common HLA haplotypes in Caucasians. As only 10% to 20% patients respond to this criterion, here we aimed at finding additional common haplotypes to improve the prediction of a successful search. HLA broad HLA-A/B/DRB1 haplotypes that were observed with frequencies ≥0.19% in patient families of European origin and that split into ≤2 predominant 4-digit HLA-A/B/C/DRB1/DQB1 haplotypes were considered as common. Carriage of at least 1 of those in 168 patients of various geographic areas with no family donor was confronted to the chance of finding ≥9/10 HLA-matched unrelated donors. Fifty common 4-digit haplotypes were identified. A higher (P < 5 × 10(-6)) chance of finding a suitable donor was found for 55 of 170 (32%) recipients that carried at least 1 of these common haplotypes. Up to now, estimates classified patients into ≥3 groups of probability with ≥1 intermediate group of poor utility for the clinicians. Considering carriage of these common haplotypes together with the frequencies of alleles and of B/C and DRB1/DQB1 associations, which are carried by patient HLA haplotypes, we could classify the patients into 2 groups of probability with a 98% and 26% chance of finding a donor, respectively. Prediction of search outcome could be improved by including the 50 most common HLA haplotypes in the current approaches.
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Antígenos HLA/genética , Trasplante de Células Madre Hematopoyéticas/métodos , Donantes de Tejidos , Alelos , Niño , Familia , Antígenos HLA/inmunología , Haplotipos , Humanos , Resultado del TratamientoRESUMEN
l-asparaginase encapsulated within erythrocytes (GRASPA(®) ) should allow serum asparagine depletion over a longer period than the native form of the enzyme, using lower doses and allowing better tolerance. The GRASPALL 2005-01 study, a multicentre randomized controlled trial, investigated three doses of GRASPA(®) for the duration of asparagine depletion in a phase I/II study in adults and children with acute lymphoblastic leukaemia (ALL) in first relapse. Between February 2006 and April 2008, 18 patients received GRASPA(®) (50 iu/kg: n = 6,100 iu/kg: n = 6, 150 iu/kg: n = 6) after randomization, and six patients were assigned to the Escherichia coli native l-asparaginase (E. colil-ASNase) control group. GRASPA(®) was effective at depleting l-asparagine. One single injection of 150 iu/kg of GRASPA(®) provided similar results to 8 × 10,000 iu/m(2) intravenous injections of E. colil-ASNase. The safety profile of GRASPA(®) showed a reduction in the number and severity of allergic reactions and a trend towards less coagulation disorders. Other expected adverse events were comparable to those observed with E. colil-ASNase and there was also no difference between the three doses of GRASPA(®) .
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Antineoplásicos/administración & dosificación , Asparaginasa/administración & dosificación , Portadores de Fármacos , Eritrocitos/enzimología , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Adulto , Antineoplásicos/efectos adversos , Antineoplásicos/sangre , Antineoplásicos/uso terapéutico , Asparaginasa/efectos adversos , Asparaginasa/sangre , Asparaginasa/uso terapéutico , Reactores Biológicos , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Sistemas de Liberación de Medicamentos , Humanos , Lactante , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Adulto JovenAsunto(s)
Enfermedades del Sistema Nervioso Autónomo/etiología , Rubor/etiología , Hipohidrosis/etiología , Neuroblastoma/cirugía , Complicaciones Posoperatorias/etiología , Ganglio Estrellado/patología , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Femenino , Rubor/diagnóstico , Humanos , Hipohidrosis/diagnóstico , Lactante , Ganglio Estrellado/cirugía , Tomografía Computarizada por Rayos XRESUMEN
Translocations involving chromosome 11q23 frequently occur in pediatric acute myeloid leukemia (AML) and are associated with poor prognosis. In most cases, the MLL gene is involved, and more than 50 translocation partners have been described. Clinical outcome data of the 11q23-rearranged subgroups are scarce because most 11q23 series are too small for meaningful analysis of subgroups, although some studies suggest that patients with t(9;11)(p22;q23) have a more favorable prognosis. We retrospectively collected outcome data of 756 children with 11q23- or MLL-rearranged AML from 11 collaborative groups to identify differences in outcome based on translocation partners. All karyotypes were centrally reviewed before assigning patients to subgroups. The event-free survival of 11q23/MLL-rearranged pediatric AML at 5 years from diagnosis was 44% (+/- 5%), with large differences across subgroups (11% +/- 5% to 92% +/- 5%). Multivariate analysis identified the following subgroups as independent prognostic predictors: t(1;11)(q21;q23) (hazard ratio [HR] = 0.1, P = .004); t(6;11)(q27;q23) (HR = 2.2, P < .001); t(10;11)(p12;q23) (HR = 1.5, P = .005); and t(10;11)(p11.2;q23) (HR = 2.5, P = .005). We could not confirm the favorable prognosis of the t(9;11)(p22;q23) subgroup. We identified large differences in outcome within 11q23/MLL-rearranged pediatric AML and novel subgroups based on translocation partners that independently predict clinical outcome. Screening for these translocation partners is needed for accurate treatment stratification at diagnosis.
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Cromosomas Humanos Par 11/genética , Reordenamiento Génico , Leucemia Mieloide Aguda/genética , Proteína de la Leucemia Mieloide-Linfoide/genética , Translocación Genética , Niño , Mapeo Cromosómico , Cromosomas Humanos Par 9/genética , Supervivencia sin Enfermedad , N-Metiltransferasa de Histona-Lisina , Humanos , Hibridación Fluorescente in Situ , Agencias Internacionales , Cariotipificación , Pronóstico , Estudios RetrospectivosRESUMEN
The Parents and Caregivers group in the face of ethics in pediatrics of the Île-de-France Ethics Area wondered about the association of the words Disability and Cancer by focusing on the study of the course of children with intellectual disability, treated for cancer. These situations are exceptional, the number of cases in France must not be more than fifty per year. We gathered the testimony of five families of children using a semi-directive survey taking up the journey from birth, announcement of the handicap, the diagnosis of cancer and its treatment. The verbatim show that each story is unique and rich in lessons, despite the feeling of "double penalty": "He did not deserve this, a handicap plus cancer is a lot for one person", "the shot moreover." A healthcare team was also interviewed and raised an additional question: "First, the double penalty then, what's the point?" Through these testimonies, we sought to question the ethical principles of care, which can be shaken up in these extraordinary supported.
Asunto(s)
Discusiones Bioéticas , Toma de Decisiones Clínicas/ética , Niños con Discapacidad , Discapacidad Intelectual , Neoplasias/terapia , Agenesia del Cuerpo Calloso/diagnóstico , Agenesia del Cuerpo Calloso/psicología , Cuidadores , Niño , Preescolar , Niños con Discapacidad/estadística & datos numéricos , Síndrome de Down/diagnóstico , Síndrome de Down/psicología , Familia/psicología , Relaciones Familiares , Femenino , Síndrome del Cromosoma X Frágil/diagnóstico , Síndrome del Cromosoma X Frágil/psicología , Francia/epidemiología , Humanos , Lactante , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/epidemiología , Discapacidad Intelectual/psicología , Masculino , Neoplasias/diagnóstico , Neoplasias/epidemiología , Neoplasias/psicología , Padres/psicología , Autonomía Personal , Investigación Cualitativa , Revelación de la VerdadRESUMEN
AIM: The aim was to describe and to analyze the ethics of decision-making in situations involving children with intellectual disability and cancer, from the referent-doctor's point-of-view, in pediatric oncology units in France. METHODS: Pediatricians working in pediatric oncology units were interviewed through an online questionnaire and a semi-directive interview was systematically proposed. We analyzed the ethical issues that arose during the process of decision-making and we made suggestions in order to address them. RESULTS: Sixteen doctors reported twenty-one clinical cases. Of these cases, one third of the children had a change in their oncologic treatment, with a risk of pejorative outcome on the prognosis. Despite the fact that ethical issues appeared in 80 % of the cases, there were few consultations with ethical committees. Decision-making process showed no difference compared to children without intellectual disability, thus raising ethical issues in the medical team. Our study showed discrepancy between frequently reported ethical issues, high consensus rate regarding treatment decision and lack of consultation with ethical committees. DISCUSSION: We propose three steps to guide the decision-making process in situations involving children with intellectual disability and cancer: 1/deeper understanding of the child through reinforced interactions with their caregivers, 2/better cross-boundary discussions, to improve the effectiveness of the multidisciplinary staff, and 3/more systematic ethical committees consultation.
Asunto(s)
Toma de Decisiones Clínicas/ética , Niños con Discapacidad , Encuestas de Atención de la Salud , Discapacidad Intelectual , Neoplasias/terapia , Adolescente , Adulto , Discusiones Bioéticas , Niño , Preescolar , Toma de Decisiones Clínicas/métodos , Consenso , Técnicas de Apoyo para la Decisión , Comités de Ética Clínica/estadística & datos numéricos , Femenino , Francia , Humanos , Lactante , Discapacidad Intelectual/complicaciones , Masculino , Neoplasias/complicaciones , Neoplasias/patología , Cuidados Paliativos , Grupo de Atención al Paciente , Medición de Riesgo , Revelación de la Verdad , Adulto JovenAsunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mieloide/genética , Síndromes Mielodisplásicos/genética , Proteínas Nucleares/genética , Trombocitopenia/genética , Regiones no Traducidas 5'/genética , Enfermedad Aguda , Salud de la Familia , Predisposición Genética a la Enfermedad/genética , Humanos , Péptidos y Proteínas de Señalización Intercelular , MutaciónRESUMEN
OBJECTIVE: To analyse parents' and children's understanding of consent information and assess their decision-making process in paediatric oncology. DESIGN: Prospective observational study. SETTINGS: Eleven French paediatric oncology units. PATIENTS: Parents and children who have been asked to give consent for participation in an early phase trial. INTERVENTIONS: Thirty-seven children and 119 parents were questioned using an audio-recorded semistructured interview. MAIN OUTCOME MEASURES: The participants' understanding of nine elements of the informed consent was assessed by comparing their answers with the informed consent leaflet. Their decision-making process was also evaluated. RESULTS: Most parents and children had an excellent understanding regarding their participation in a clinical trial (respectively 88.2% and 48.6%), the right to withdraw (76.5% and 43.2%) and the prospects of collective benefits (74.8% and 48.6%). By contrast, less than half of the parents and few of the children correctly understood the alternatives (respectively 47.5% and 27%), the risks related to participation (44.5% and 10.8%), the prospects of individual benefits (33.6% and 10.8%) and the purpose of the clinical trial (12.6% and 2.7%). Twenty-six (70.3%) children participated in the decision-making process. Most parents and children felt they had no choice but to participate in the trial to have access to a new anticancer treatment. CONCLUSIONS: What might appear to be a poor understanding of the research protocol may actually correspond to the families' interpretation of the situation as a coping mechanism. All children (except infants) should get age-tailored information in order for them to have a meaningful involvement in research.
Asunto(s)
Ensayos Clínicos Fase I como Asunto , Comprensión , Toma de Decisiones , Consentimiento Informado , Padres , Participación del Paciente , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Neoplasias/terapia , Estudios ProspectivosRESUMEN
Since neuroblastoma occurs very early in children's lives, it has been hypothesized that pre- and perinatal factors may play a role in its etiology. This study investigated the role of birth characteristics, congenital malformation and maternal reproductive history in neuroblastoma. The data used were generated by the national population-based case-control study, ESCALE, conducted in France in 2003-2004. The mothers of 191 neuroblastoma cases and 1,681 controls, frequency-matched by age and gender, were interviewed by telephone, using a standardized questionnaire, on several factors including pregnancy, medical history, lifestyle, childhood medical conditions and exposures. A positive association between congenital malformation and all neuroblastoma cases was observed [Odds ratio (OR) = 2.2, 95% confidence interval (95% CI): 1.1-4.5]. Congenital malformations were highly associated to neuroblastoma in children aged less than 1 year (OR = 16.8, 95% CI: 3.1-90), while no association was observed in children aged 1 year or more (OR = 1.0, 95% CI: 0.3-2.9). A negative association with a maternal history of spontaneous abortions was also found (OR = 0.6, 95% CI: 0.4-0.9). The results strongly support the hypothesis that congenital anomalies may be associated with neuroblastoma, particularly in infant (less than 1 year of age).
Asunto(s)
Peso al Nacer , Anomalías Congénitas/diagnóstico , Neuroblastoma/diagnóstico , Historia Reproductiva , Adolescente , Adulto , Orden de Nacimiento , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Francia/epidemiología , Edad Gestacional , Humanos , Lactante , Masculino , Edad Materna , Embarazo , Factores Socioeconómicos , Encuestas y CuestionariosRESUMEN
Is it necessary--and possible--to discuss death with a terminally ill child? How should one approach the subject? A recent Swedish study demonstrates the benefits for parents who discuss with their child his or her imminent death, and examines the ways in which caregivers can help such parents. The mother of one child treated in our unit recently wrote a story 48 hours before her child's death. The story served to broach a number of questions often raised by dying children and their families: fear of the unknown, of being replaced, the inevitability of death, grief and fear of being forgotten... Since 2004, the story has been given to several families with dying children in our unit. In order to evaluate the story's impact on families and to determine whether a document which stimulates dialogue should continue to be given to parents, we asked the first thirteen to fill out a questionnaire. The results confirmed that the story was experienced as something positive and that it helped parents to talk with their children. The results of our study lead us to conclude that the medical profession should lend its full support to families who wish to engage in this dialogue with their children. This study also raises many questions and should be part of a global accompaniment strategy. With our support, an illustrated story book called Falikou was published in October 2006.