RESUMEN
Thromboembolism is a serious complication of induction therapy for childhood acute lymphoblastic leukemia. We prospectively compared the efficacy and safety of antithrombotic interventions in the consecutive leukemia trials ALL-BFM 2000 and AIEOP-BFM ALL 2009. Patients with newly diagnosed acute lymphoblastic leukemia (n=949, age 1 to 18 years) were randomized to receive low-dose unfractionated heparin, prophylactic low molecular weight heparin (enoxaparin) or activity-adapted antithrombin throughout induction therapy. The primary objective of the study was to determine whether enoxaparin or antithrombin reduces the incidence of thromboembolism as compared to unfractionated heparin. The principal safety outcome was hemorrhage; leukemia outcome was a secondary endpoint. Thromboembolism occurred in 42 patients (4.4%). Patients assigned to unfractionated heparin had a higher risk of thromboembolism (8.0%) compared with those randomized to enoxaparin (3.5%; P=0.011) or antithrombin (1.9%; P<0.001). The proportion of patients who refused antithrombotic treatment as allocated was 3% in the unfractionated heparin or antithrombin arms, and 33% in the enoxaparin arm. Major hemorrhage occurred in eight patients (no differences between the groups). The 5-year event-free survival was 80.9±2.2% among patients assigned to antithrombin compared to 85.9±2.0% in the unfractionated heparin group (P=0.06), and 86.2±2.0% in the enoxaparin group (P=0.10). In conclusion, prophylactic use of antithrombin or enoxaparin significantly reduced thromboembolism. Despite the considerable number of patients rejecting the assigned treatment with subcutaneous injections, the result remains unambiguous. Thromboprophylaxis - for the present time primarily with enoxaparin - can be recommended for children and adolescents with acute lymphoblastic leukemia during induction therapy. Whether and how antithrombin may affect leukemia outcome remains to be determined.
Asunto(s)
Antitrombinas/administración & dosificación , Heparina de Bajo-Peso-Molecular/administración & dosificación , Heparina/administración & dosificación , Quimioterapia de Inducción , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Tromboembolia/prevención & control , Adolescente , Antitrombinas/efectos adversos , Niño , Preescolar , Femenino , Heparina/efectos adversos , Heparina de Bajo-Peso-Molecular/efectos adversos , Humanos , Lactante , Masculino , Estudios ProspectivosRESUMEN
The prognosis in children with refractory or relapsed (r/r) T-cell acute lymphoblastic leukaemia (T-ALL) or lymphoblastic lymphoma (T-LBL) is poor. Nelarabine (Ara-G) has successfully been used as salvage therapy in these children, but has been associated with significant, even fatal, neurotoxicities. We retrospectively analysed 52 patients with r/r T-ALL/T-LBL aged ≤19 years who were treated with Ara-G alone (n = 25) or in combination with cyclophosphamide and etoposide (n = 27). The majority of patients (45/52) received 1-2 cycles of Ara-G. Seventeen patients (32·7%) had refractory disease, 28 (53·8%) were in first relapse and 7 (13·5%) were in second relapse. A response to Ara-G was achieved in 20 patients and 15 (28·8%) were in remission at last follow-up. Twelve patients (23·1%) had neurotoxic adverse effects (neuro-AE) of any grade, of whom 7 (13·5%) developed neurotoxicity ≥ grade III. The most frequent neuro-AEs were peripheral motor neuropathy (19·2%), peripheral sensory neuropathy (11·5%) and seizures (9·6%). Three patients died of central neuro-AE after 1-2 cycles of combination therapy. Patients with neurotoxicity were significantly older (median 15·17 years) than those without (10·34 years, P = 0·017). No differences were observed between mono- and combination therapy concerning outcome and neuro-AE. The incidence of neuro-AE was not associated with concurrent intrathecal therapy or prior central nervous system irradiation.
Asunto(s)
Arabinonucleósidos/efectos adversos , Neoplasias Hematológicas/tratamiento farmacológico , Neoplasias Hematológicas/epidemiología , Síndromes de Neurotoxicidad/epidemiología , Linfocitos T , Adolescente , Adulto , Factores de Edad , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Arabinonucleósidos/administración & dosificación , Niño , Preescolar , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Estudios de Seguimiento , Neoplasias Hematológicas/patología , Humanos , Masculino , Síndromes de Neurotoxicidad/patología , Estudios RetrospectivosRESUMEN
Haemophagocytic lymphohistiocytosis (HLH) in the context of malignancy is mainly considered a challenge of adult haematology. While this association is also observed in children, little is known regarding inciting factors, appropriate treatment and prognosis. We retrospectively analysed 29 paediatric and adolescent patients for presenting features, type of neoplasm or preceding chemotherapy, treatment and outcome. Haemophagocytic lymphohistiocytosis was considered triggered by the malignancy (M-HLH) in 21 patients, most of whom had T- (n = 12) or B-cell neoplasms (n = 7), with Epstein-Barr virus as a co-trigger in five patients. In eight patients, HLH occurred during chemotherapy (Ch-HLH) for malignancy, mainly acute leukaemias (n = 7); an infectious trigger was found in seven. In M- and Ch-HLH, median overall survival was 1·2 and 0·9 years, and the 6 month survival rates were 67% and 63%, respectively. Seven of 11 deceased M-HLH patients exhibited active malignancy and HLH at the time of death, while only two out of five deceased Ch-HLH patients had evidence of active HLH. To overcome HLH, malignancy- and HLH-directed treatments were administered in the M-HLH cohort; however, it was not possible to determine superiority of one approach over the other. For Ch-HLH, treatment ranged from postponement of chemotherapy to the use of etoposide-containing regimens.
Asunto(s)
Infecciones por Virus de Epstein-Barr , Leucemia , Linfohistiocitosis Hemofagocítica , Enfermedad Aguda , Adolescente , Adulto , Niño , Preescolar , Supervivencia sin Enfermedad , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Infecciones por Virus de Epstein-Barr/mortalidad , Femenino , Humanos , Lactante , Recién Nacido , Leucemia/tratamiento farmacológico , Leucemia/mortalidad , Linfohistiocitosis Hemofagocítica/etiología , Linfohistiocitosis Hemofagocítica/mortalidad , Linfohistiocitosis Hemofagocítica/terapia , Masculino , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Long-term treatment with 6-thioguanine (6-TG) for pediatric acute lymphoblastic leukemia (ALL) is associated with high rates of hepatic sinusoidal obstruction syndrome (SOS). Nevertheless, current treatment continues to use short-term applications of 6-TG with only sparse information on toxicity. 6-TG is metabolized by thiopurine methyltransferase (TPMT) which underlies clinically relevant genetic polymorphism. We analyzed the association between hepatic SOS reported as a serious adverse event (SAE) and short-term 6-TG application in 3983 pediatric ALL patients treated on trial AIEOP-BFM ALL 2000 (derivation cohort) and defined the role of TPMT genotype in this relationship. We identified 17 patients (0.43%) with hepatic SOS, 13 of which with short-term exposure to 6-TG (P < 0.0001). Eight of the 13 patients were heterozygous for low-activity TPMT variants, resulting in a 22.4-fold (95% confidence interval 7.1-70.7; P ≤ 0.0001) increased risk of hepatic SOS for heterozygotes in comparison to TPMT wild-type patients. Results were supported by independent replication analysis. All patients with hepatic SOS after short-term 6-TG recovered and did not demonstrate residual symptoms. Thus, hepatic SOS is associated with short-term exposure to 6-TG during treatment of pediatric ALL and SOS risk is increased for patients with low-activity TPMT genotypes.
Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Enfermedad Veno-Oclusiva Hepática/prevención & control , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Tioguanina/administración & dosificación , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Pronóstico , Factores de TiempoRESUMEN
INTRODUCTION: Extracranial rhabdoid tumours are rare, highly aggressive malignancies primarily affecting young children. The EU-RHAB registry was initiated in 2009 to prospectively collect data of rhabdoid tumour patients treated according to the EU-RHAB therapeutic framework. METHODS: We evaluated 100 patients recruited within EU-RHAB (2009-2018). Tumours and matching blood samples were examined for SMARCB1 mutations by sequencing and cytogenetics. RESULTS: A total of 70 patients presented with extracranial, extrarenal tumours (eMRT) and 30 with renal rhabdoid tumours (RTK). Nine patients demonstrated synchronous tumours. Distant metastases at diagnosis (M+) were present in 35% (35/100), localised disease (M0) with (LN+) and without (LN-) loco-regional lymph node involvement in 65% (65/100). SMARCB1 germline mutations (GLM) were detected in 21% (17/81 evaluable) of patients. The 5-year overall survival (OS) and event-free survival (EFS) rates were 45.8 ± 5.4% and 35.2 ± 5.1%, respectively. On univariate analyses, age at diagnosis (≥12 months), M0-stage, absence of synchronous tumours, absence of a GLM, gross total resection (GTR), radiotherapy and achieving a CR were significantly associated with favourable outcomes. In an adjusted multivariate model presence of a GLM, M+ and lack of a GTR were the strongest significant negative predictors of outcome. CONCLUSIONS: We suggest to stratify patients with localised disease (M0), GTR+ and without proof of a GLM (5-year OS 72.2 ± 9.9%) as 'standard risk'. Patients presenting with one of the features M+ and/or GTR- and/or GLM+ belong to a high risk group (5-year, OS 32.5 ± 6.2%). These patients need novel therapeutic strategies such as combinations of targeted agents with conventional chemotherapy or novel experimental approaches ideally within international phase I/II trials.
Asunto(s)
Tumor Rabdoide/epidemiología , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Factores de RiesgoRESUMEN
The identification and characterization of rare immune cell populations in humans can be facilitated by their growth advantage in the context of specific genetic diseases. Here, we use autoimmune lymphoproliferative syndrome to identify a population of FAS-controlled TCRαß+ T cells. They include CD4+, CD8+, and double-negative T cells and can be defined by a CD38+CD45RA+T-BET- expression pattern. These unconventional T cells are present in healthy individuals, are generated before birth, are enriched in lymphoid tissue, and do not expand during acute viral infection. They are characterized by a unique molecular signature that is unambiguously different from other known T cell differentiation subsets and independent of CD4 or CD8 expression. Functionally, FAS-controlled T cells represent highly proliferative, noncytotoxic T cells with an IL-10 cytokine bias. Mechanistically, regulation of this physiological population is mediated by FAS and CTLA4 signaling, and its survival is enhanced by mTOR and STAT3 signals. Genetic alterations in these pathways result in expansion of FAS-controlled T cells, which can cause significant lymphoproliferative disease.
Asunto(s)
ADP-Ribosil Ciclasa 1/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Antígenos Comunes de Leucocito/metabolismo , Receptor fas/inmunología , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Activación de Linfocitos/inmunología , Trastornos Linfoproliferativos/inmunología , Masculino , Persona de Mediana Edad , Transducción de Señal/inmunología , Adulto JovenRESUMEN
Osteonecrosis (ON) is a common and debilitating side effect of anti-leukemic treatment in children with acute lymphoblastic leukemia (ALL). However, the impact of leukemia itself on ON development remains elusive. We analyzed 76 children enrolled in the ongoing OPAL trial, who had magnetic resonance imaging (MRI) studies at diagnosis. MRI screening revealed 14 osteonecrotic lesions (5 × hips, 9 × knees) of any grade (I-III) in 7 (9.2%) patients. Six months on, the number of ON per patient increased (1 patient), remained constant (2), and decreased (2). The severity increased from grade I to II in two patients, remained constant (1), completely resolved (2), and decreased from grade III to osteoedema (1). No differences between adolescents initially presenting with/without ON were observed concerning age, pubertal stage, body mass index, leukemia characteristics, and clinical presentation. In MRI screening, a remarkable number of adolescents with ALL present with ON at diagnosis. The course of these ON remains highly unpredictable.
Asunto(s)
Huesos/patología , Osteonecrosis/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Adolescente , Huesos/diagnóstico por imagen , Niño , Progresión de la Enfermedad , Femenino , Humanos , Incidencia , Imagen por Resonancia Magnética , Masculino , Osteonecrosis/epidemiología , Osteonecrosis/etiología , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Infections are a major cause of morbidity and mortality in childhood acute lymphoblastic leukemia (ALL) and only limited information is available on infectious complications. PATIENTS AND METHODS: We investigated infectious complications in 293 children during different treatment phases of the multicenter protocol COALL-06-97. We also evaluated whether therapy reduction in prognostically good risk patients receiving either the low risk or high risk treatment arm would lead to fewer infectious complications. RESULTS: Thirty of 293 patients had no infections; 263 patients had 682 infectious complications (median 2, range 1-9), five of them lethal. Two thirds of the infections occurred during periods of neutropenia. The most frequent infectious episodes were fever of unknown origin (FUO): 483/682 (70.8%), microbiologically documented infections (MDI): 100/682 (14.6%), (61 gram-positive, 36 gram-negative, 3 fungal isolates), and clinically documented infections (CDI): 99/682 (14.5%). With standard reinduction, 44% low risk and 57% high risk patients had infections versus 26% low risk and 38% high risk patients with reduced reinduction therapy (P < 0.01). CONCLUSIONS: Most patients treated with intensive combination therapy for ALL experience one to several serious infections during treatment. The wide range in number of infectious episodes and the lack of infections in a small subset of patients in spite of uniform treatment suggest genetic as well as possibly environmental factors to have a role. Moderate reduction of chemotherapy may significantly reduce the rate of infectious episodes.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Infecciones/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/microbiología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Niño , Preescolar , Femenino , Humanos , Lactante , Infecciones/inducido químicamente , Masculino , Factores de Riesgo , Resultado del TratamientoRESUMEN
Osteonecrosis (ON) is a debilitating side effect of anti-leukemic treatment. Thus far, the role of leukemic infiltration (LI) of bone is unclear. The first 30 children aged ≥10 years, who were enrolled in the ongoing OPAL trial and had MRI studies at diagnosis and at 6 months, were analyzed. MRI revealed extensive LIs in 24 (80%) patients. The signal abnormalities changed back to a physiological signal in 29 out of 30 children at 6 months. Of the 24 children with LIs at diagnosis, 3 (12.5%) developed ON ≥ II, whereas 4 (66.7%) patients without LIs subsequently developed ON ≥ II (p = .016). No differences between children initially presenting with/without LIs were observed concerning age, pubertal stage, white blood count, immunophenotype, and clinical presentation. Initial radiological LI of bone and, thus, single MRI at diagnosis cannot identify children at high risk of developing radiological ON at 6 months into treatment.
Asunto(s)
Antineoplásicos , Infiltración Leucémica , Osteonecrosis , Leucemia-Linfoma Linfoblástico de Células Precursoras , Antineoplásicos/efectos adversos , Niño , Humanos , Imagen por Resonancia Magnética , Osteonecrosis/inducido químicamente , Osteonecrosis/diagnóstico por imagen , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico por imagen , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológicoRESUMEN
Prognosis in childhood craniopharyngioma survivors hinges upon late effects such as pituitary deficiency and obesity. Observations indicate that reduced physical activity and increased daytime sleepiness might be risk factors for obesity. We analyzed the degree of daytime sleepiness in 115 childhood craniopharyngioma patients (47% obese) using the Epworth Sleepiness Scale (ESS). Thirty-five (30%) displayed increased daytime sleepiness (ESS score > 10) of whom 14 were obese (26% of obese cohort). Polysomnography (PSG) and Multiple Sleep Latency Tests (MSLT) were conducted with 10 obese patients presenting increased daytime sleepiness, with only two craniopharyngioma patients revealing a sleep related breathing disorder. Four patients had repeated episodes of SOREM (sleep onset rapid eye movement), the classic PSG criterion for narcolepsy. Three patients displayed hypersomnia. All but one patient qualified as acutely obese. We speculate that secondary narcolepsy is an exacerbating condition of childhood craniopharyngioma obesity, supported by recent reports on orexin and narcolepsy which suggest hypothalamic failure in idiopathic narcolepsy.
Asunto(s)
Craneofaringioma/complicaciones , Narcolepsia/etiología , Obesidad/complicaciones , Neoplasias Hipofisarias/complicaciones , Adolescente , Adulto , Índice de Masa Corporal , Estimulantes del Sistema Nervioso Central/uso terapéutico , Niño , Estudios de Cohortes , Femenino , Antígenos HLA/metabolismo , Humanos , Masculino , Narcolepsia/tratamiento farmacológico , Polisomnografía , Factores de Riesgo , Sueño/fisiología , Fases del SueñoRESUMEN
We analyzed whether childhood craniopharyngioma predisposes to obesity and growth impairment. Height/length, body mass index (BMI), and hypothalamic involvement were evaluated in 90 patients at standardized ages and time points before, after, and at the time of diagnosis. Relevant decreases in height sd score (SDS) started at 10-12 months of age and persisted until diagnosis of childhood craniopharyngioma. Relevant increases in BMI SDS were detectable between 4 and 5 yr of age. Postoperative BMI SDS (yr 1-6) had a weak positive correlation with BMI SDS at the time of diagnosis. In linear regression analysis, hypothalamic tumor involvement (P < 0.001), ponderal index at birth (P = 0.014), and BMI SDS at age 6-7 months (P = 0.029) and at age 5 yr (P < 0.001) had relevant and independent impacts on the development of obesity. Patients with hypothalamic involvement (n = 48) presented lower ponderal index and BMI SDS at birth and higher BMI SDS at the time of diagnosis (P < 0.001) as well as during annual follow-up (P < 0.001) compared with patients without hypothalamic involvement (n = 42). From childhood (3.5-4 yr) to the time of diagnosis, growth rates were reduced for patients with hypothalamic tumor involvement. Patients without hypothalamic involvement presented reduced growth rates in early infancy (age 10-12 months) that persisted until diagnosis. We conclude that reduced growth rates occur quite early in history; BMI SDS increases occur later and are predictive of obesity. Hypothalamic involvement is the major risk factor for obesity in patients with childhood craniopharyngioma.
Asunto(s)
Índice de Masa Corporal , Desarrollo Infantil , Craneofaringioma/complicaciones , Trastornos del Crecimiento/etiología , Obesidad/etiología , Neoplasias Hipofisarias/complicaciones , Estatura , Peso Corporal , Craneofaringioma/patología , Craneofaringioma/fisiopatología , Craneofaringioma/cirugía , Susceptibilidad a Enfermedades , Humanos , Hipotálamo/patología , Lactante , Estudios Longitudinales , Análisis Multivariante , Invasividad Neoplásica , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/fisiopatología , Neoplasias Hipofisarias/cirugía , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Controversies surround various treatment variables for patients with childhood craniopharyngioma such as growth hormone (GH) replacement, which some believe can exacerbate recurrence/progression. We prospectively assessed the risk of tumor recurrence/progression in survivors of childhood craniopharyngioma. METHODS: Multivariable analyses of risk factors (age at diagnosis, degree of resection, irradiation, GH treatment and gender) and descriptive analyses of overall survival (OS) and event-free survival (EFS) rates were performed in 117 patients, recruited prospectively and evaluated after 3 years of follow-up in the German, Austrian and Swiss multicenter trial KRANIOPHARYNGEOM 2000. RESULTS: We observed a 3-year OS of 0.97 and a 3-year EFS of 0.46, indicating high recurrence rates after complete resection (CR) (n = 47; 3-year-EFS: 0.64) and high progression rates after incomplete resection (IR) (n = 64; 3-year EFS: 0.31). The risk of an event decreased by 80% after CR compared to IR (hazard ratio = 0.20; p < 0.001). Irradiation had protective effects on EFS: irradiated patients had an 88% lower risk of recurrence/progression compared to patients without/before irradiation (hazard ratio = 0.12; p < 0.001). GH treatment had no impact on 3-year EFS rates. CONCLUSIONS: Tumor recurrences/progressions are frequent and occur early after initial treatment of childhood craniopharyngioma. A radical resection preserving the integrity of hypothalamic structures appears optimal at original diagnosis. Irradiation was efficient in preventing recurrences/progressions. GH treatment had no impact on the low 3-year EFS observed in our study. However, further conclusions on the influence of GH on recurrence rates have to be refined to long-term follow-up studies of patients with childhood craniopharyngioma.
Asunto(s)
Craneofaringioma/terapia , Neoplasias Hipofisarias/terapia , Adolescente , Niño , Preescolar , Craneofaringioma/tratamiento farmacológico , Craneofaringioma/radioterapia , Craneofaringioma/cirugía , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Lactante , Masculino , Análisis Multivariante , Recurrencia Local de Neoplasia/prevención & control , Neoplasias Hipofisarias/tratamiento farmacológico , Neoplasias Hipofisarias/radioterapia , Neoplasias Hipofisarias/cirugía , Estudios Prospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
Craniopharyngioma is a rare dysontogenetic benign tumor. Patients frequently suffer from endocrine deficiencies, sleep disturbances and obesity due to pituitary and hypothalamic lesions. A self-assessment daytime sleepiness questionnaire (German version of the Epworth Sleepiness Scale [ESS]) was used to evaluate 79 patients with childhood craniopharyngioma. Because hypothalamic lesions may explain daytime sleepiness in craniopharyngioma patients, salivary melatonin and cortisol concentrations were examined in severely obese (BMI>or=4SD) and non severely obese (BMI<4SD) craniopharyngioma patients (n=79), patients with hypothalamic pilocytic astrocytoma (n=19), and control subjects (n=30). Using a general linear model procedure analyzing the influence of BMI and tumor diagnosis on diurnal salivary melatonin we found that morning salivary melatonin levels were related to BMI (F test: p-value=0.004) and tumor diagnosis (F-test: p-value=0.032). Also for nighttime salivary melatonin levels significant relations with BMI (p-value in F-test: <0.001) and tumor diagnosis (p-value in F-test: 0.025) were detectable. Melatonin concentrations in saliva of craniopharyngioma patients collected at nighttime or in the morning showed a negative correlation (Spearman's rho: -0.42; p=0.001; Spearman's rho: -0.31; p=0.020) with the patient's ESS score. Severely obese craniopharyngioma patients and severely obese hypothalamic tumor patients had similar patterns of melatonin secretion. Differences in terms of diurnal salivary cortisol concentrations were not detectable when patient groups and controls were compared. As decreased nocturnal melatonin levels were associated with increased daytime sleepiness, BMI and hypothalamic tumor diagnosis, we initiated an experimental melatonin substitution in 10 adult obese patients (5f/5m) with childhood craniopharyngioma. In all 10 patients with childhood craniopharyngioma the degree of daytime sleepiness significantly improved based on activity diaries, ESS, self assessment questionnaires and actimetry. We speculate that hypothalamic lesions might be responsible for both obesity and daytime sleepiness. As first experiences with experimental melatonin substitution were promising, further randomized double-blinded studies on the beneficial effects of melatonin substitution on daytime sleepiness and weight control in these patients are warranted.
Asunto(s)
Craneofaringioma/metabolismo , Melatonina/metabolismo , Melatonina/uso terapéutico , Obesidad/metabolismo , Neoplasias Hipofisarias/metabolismo , Fases del Sueño , Adolescente , Adulto , Astrocitoma/complicaciones , Astrocitoma/metabolismo , Niño , Preescolar , Ritmo Circadiano , Craneofaringioma/complicaciones , Trastornos de Somnolencia Excesiva/complicaciones , Trastornos de Somnolencia Excesiva/tratamiento farmacológico , Femenino , Humanos , Hidrocortisona/sangre , Neoplasias Hipotalámicas/metabolismo , Masculino , Obesidad/complicaciones , Neoplasias Hipofisarias/complicaciones , Saliva/química , Fases del Sueño/efectos de los fármacosRESUMEN
Craniopharyngiomas are rare dysontogenetic malformations. As the survival rate after craniopharyngioma diagnosed during childhood and adolescence is high, prognosis and quality of life (QoL) in survivors mainly depend on adverse late effects such as hypopituitarism and obesity. Appropriate laboratory diagnostics of endocrine deficiencies and sufficient hormonal substitution have significant impact on prognosis and QoL. In order to evaluate and standardize diagnostic and therapeutical strategies in childhood craniopharyngioma the prospective multicenter surveillance study KRANIOPHARYNGEOM 2000 was initiated for patients diagnosed with craniopharyngioma during childhood and adolescence. We are reporting on current strategies for laboratory diagnostics and endocrine substitution in patients with childhood craniopharyngioma recruited in KRANIOPHARYNGEOM 2000.
Asunto(s)
Craneofaringioma/diagnóstico , Craneofaringioma/terapia , Diabetes Insípida Neurogénica/diagnóstico , Diabetes Insípida Neurogénica/terapia , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/terapia , Adolescente , Adulto , Niño , Craneofaringioma/complicaciones , Diabetes Insípida Neurogénica/etiología , Femenino , Alemania , Humanos , Lactante , Recién Nacido , Masculino , Obesidad/diagnóstico , Obesidad/etiología , Obesidad/terapia , Neoplasias Hipofisarias/complicaciones , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina , Resultado del TratamientoRESUMEN
RATIONALE: We analyzed the impact of tumour localization and histology on functional capacity (FC) and body mass index (BMI) in children with sellar masses. METHODS: FC was evaluated using the ability scale Fertigkeitenskala Münster-Heidelberg in 403 children and adolescents with sellar masses (276 craniopharyngioma, 14 germinoma, 21 optic/chiasmatic glioma, 40 hypothalamic glioma, 13 cysts of Rathke's cleft and 39 other sellar masses). Besides tumour localization, the influence of gender, irradiation and age at diagnosis and at evaluation on FC and BMI was analyzed. General linear models with explanatory influential variables were built. RESULTS: In multivariate analysis, only age at diagnosis (p<0.001) and hypothalamic involvement (p=0.005) had relevant impact on FC. The second model showed BMI at diagnosis (p<0,001), hypothalamic involvement (p<0.001) and craniopharyngioma (p=0,004) to influence BMI at the latest evaluation. CONCLUSION: We conclude that hypothalamic involvement and young age at diagnosis had major impact on FC and BMI and should be considered as risk factors for impaired rehabilitation.
Asunto(s)
Índice de Masa Corporal , Craneofaringioma/diagnóstico , Craneofaringioma/fisiopatología , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/fisiopatología , Adolescente , Adulto , Distribución de Chi-Cuadrado , Niño , Craneofaringioma/clasificación , Estudios Transversales , Femenino , Humanos , Hipotálamo/patología , Hipotálamo/fisiopatología , Masculino , Pruebas Neuropsicológicas , Neoplasias Hipofisarias/clasificación , Estudios Prospectivos , Calidad de Vida , Estudios RetrospectivosRESUMEN
OBJECTS: We longitudinally analysed functional capacity and quality of life (QoL) in 102 patients with a childhood craniopharyngioma during follow-up. METHODS: The Fertigkeitenskala Münster-Heidelberg (FMH) ability scale was used for QoL assessment. Multivariate analysis evaluated FMH scores at various time points, examining hypothalamus involvement (HI), body mass index (BMI), degree of resection, tumour progression, relapse and irradiation. RESULTS AND CONCLUSION: Patients without HI (n=60) self-assessed higher QoL at baseline (p=0.001) and follow-up (p<0.001) than patients with HI (n=42). Only patients without HI evaluated at baseline >12 months after diagnosis showed longitudinal improvement in FMH scores (p=0.040). Rates of incomplete resection and irradiation were higher (p=0.070 and p=0.002 respectively) in patients with HI. In multivariate analysis, only HI, tumour relapse, progression, baseline FMH score, and time between diagnosis and baseline evaluation had independent impact on QoL. HI, tumour progression, and relapse had long-term QoL affects-most notably, severe obesity.