RESUMEN
BACKGROUND: The surgical treatment of Ewing's sarcoma family tumours (ESFTs) is challenging especially with axial tumours. The aim of the study was to analyse surgical treatment and outcome in a nationwide, population-based material consisting of surgically treated axial and peripheral ESFTs of bone and soft tissue. METHODS: The data were collected from the Finnish National Cancer Registry and the medical records of patients diagnosed during 1990-2009. Fifty-seven patients with surgically treated ESFTs were included, 22 with an axial and 35 with a peripheral primary tumours. The surgical treatment, its complications, survival and prognostic factors were analysed. RESULTS: Fifty-four patients underwent surgery with a curative intent and three underwent de-bulking operations. Bone reconstruction was performed in six patients with an axial and 15 with a peripheral tumour. Positive resection margins were associated with a worse five-year local relapse-free survival (33% vs. 84% for those with resection margins free of tumour cells, p = 0.003). The five-year sarcoma-specific survival was affected only by an axial location of the primary (61% vs. 89% for those with a peripheral tumour, p = 0.031). The late complications were mainly associated with bone reconstruction and more frequent among patients with a peripheral compared to an axial tumour (p = 0.031). CONCLUSIONS: In the treatment of ESFTs, achieving adequate resection margins is crucial to avoid local relapses. Surgical complications are common particularly with bone reconstruction.
Asunto(s)
Neoplasias Óseas/cirugía , Huesos/patología , Huesos/cirugía , Recuperación del Miembro , Sarcoma de Ewing/cirugía , Adolescente , Adulto , Neoplasias Óseas/radioterapia , Huesos de la Extremidad Inferior/patología , Huesos de la Extremidad Inferior/cirugía , Huesos de la Extremidad Superior/patología , Huesos de la Extremidad Superior/cirugía , Niño , Preescolar , Supervivencia sin Enfermedad , Fraccionamiento de la Dosis de Radiación , Femenino , Finlandia , Estudios de Seguimiento , Humanos , Recuperación del Miembro/estadística & datos numéricos , Masculino , Registros Médicos , Modelos de Riesgos Proporcionales , Radioterapia Adyuvante , Sistema de Registros , Estudios Retrospectivos , Sarcoma de Ewing/radioterapia , Columna Vertebral/patología , Columna Vertebral/cirugía , Resultado del Tratamiento , Adulto JovenRESUMEN
We determined the genome-wide digital gene expression (DGE) profiles of primary acute lymphoblastic leukemia (ALL) cells from 21 patients taking advantage of 'second-generation' sequencing technology. Patients included in this study represent four cytogenetically distinct subtypes of B-cell precursor (BCP) ALL and T-cell lineage ALL (T-ALL). The robustness of DGE combined with supervised classification by nearest shrunken centroids (NSC) was validated experimentally and by comparison with published expression data for large sets of ALL samples. Genes that were differentially expressed between BCP ALL subtypes were enriched to distinct signaling pathways with dic(9;20) enriched to TP53 signaling, t(9;22) to interferon signaling, as well as high hyperdiploidy and t(12;21) to apoptosis signaling. We also observed antisense tags expressed from the non-coding strand of ~50% of annotated genes, many of which were expressed in a subtype-specific pattern. Antisense tags from 17 gene regions unambiguously discriminated between the BCP ALL and T-ALL subtypes, and antisense tags from 76 gene regions discriminated between the 4 BCP subtypes. We observed a significant overlap of gene regions with alternative polyadenylation and antisense transcription (P<1 × 10(-15)). Our study using DGE profiling provided new insights into the RNA expression patterns in ALL cells.
Asunto(s)
Biomarcadores de Tumor/genética , Perfilación de la Expresión Génica , Regulación Leucémica de la Expresión Génica , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Pronóstico , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Some attempts have been made to reduce the costs incurred in the therapy of leukaemia, but no studies are available regarding costs of the entire treatment in children with acute lymphocytic leukaemia (ALL). We analysed all the direct costs of treatment of 11 children with ALL diagnosed and treated in Kuopio University Hospital. The follow-up continued from diagnosis until the end of treatment for each patient. Patient treatment on the ward lasted for 84-210 d and in the outpatient clinic for 24-66 d, depending on the risk group. From 11-54 of the inpatient days were required for the treatment of infections. Total mean cost of the entire treatment was US $103250 (US $55196-166039) per patient, 53% of which were basic hospital costs and 47% patient-specific costs. Laboratory tests and radiology accounted for 18% of all direct costs and cytostatic drugs for 13%, but blood products accounted for only 4% of the total. Infections were the most important extra cause of costs, accounting for 18% of the mean total costs per patient. The complete treatment of a child with ALL came to a total of US $103250. However, since 80% of children with ALL are long-term survivors, the cost must be regarded as a good investment.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Costos de Hospital/estadística & datos numéricos , Hospitales Universitarios/economía , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/economía , Adolescente , Niño , Preescolar , Costos y Análisis de Costo , Costos Directos de Servicios , Femenino , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Medición de Riesgo , SueciaRESUMEN
BACKGROUND: Our purpose was to increase the dose intensity of chemotherapy and reduce the days with neutropenic fever in childhood high-risk (HR) acute lymphoblastic leukemia (ALL) by systematic use of granulocyte-macrophage colony-stimulating factor (GM-CSF). PROCEDURE: All children with HR-ALL in Finland during 1990-1996 were included. Two open-label study groups were formed: 1) 34 children diagnosed between January, 1992, and December, 1996, received seven or nine courses (depending on cranial RT or no cranial RT) of GM-CSF at 5 microg/kg s.c. daily until an absolute neutrophil count (ANC) of 1,000 x 10(6)/liter at scheduled places in the protocol and 2) 80 control children, those diagnosed between January, 1990, and December, 1991, plus all with significant coexpression of myeloid markers, did not receive GM-CSF. RESULTS: Dose intensity increased in patients who received regular GM-CSF support. The intensive phase of therapy, including induction, consolidation courses, and delayed intensification, was 33 days shorter (P < 0.001) in children with seven courses and 26 days shorter (P < 0.01) in those with nine courses of GM-CSF compared to controls. The number of infections during the whole ALL therapy was reduced by use of GM-CSF in children aged >5 years (P < 0.001), but not in those aged <5 years. The mean total duration of intravenous antibiotics per child was 39 days in the GM-CSF group and 48 days in the control group (P < 0. 001). Systematic use of GM-CSF was cost-effective. CONCLUSIONS: Systematic use of GM-CSF improved dose intensity by shortening the intensive treatment period by about 4 weeks. Use of GM-CSF reduced the days for inpatient antibiotics by about 1 week per child, which translates into reduced costs.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Fiebre/prevención & control , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Neutropenia/prevención & control , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Factores de Edad , Antibacterianos/administración & dosificación , Antibacterianos/economía , Antibacterianos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Infecciones Bacterianas/prevención & control , Niño , Preescolar , Estudios de Cohortes , Análisis Costo-Beneficio , Irradiación Craneana , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos y Macrófagos/economía , Humanos , Lactante , Inyecciones Intravenosas , Tiempo de Internación/economía , Recuento de Leucocitos , Modelos Lineales , Masculino , Neutrófilos/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Biomarcadores de Tumor/sangre , Hepatoblastoma/sangre , Neoplasias Hepáticas/sangre , Fragmentos de Péptidos/sangre , Procolágeno/sangre , Antígeno Ca-125/sangre , Antígeno CA-19-9/sangre , Niño , Preescolar , Femenino , Estudios de Seguimiento , Hepatoblastoma/tratamiento farmacológico , Hepatoblastoma/cirugía , Humanos , Lactante , Recién Nacido , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Masculino , alfa-Fetoproteínas/análisisAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Herpesvirus Humano 4 , Inmunosupresores/efectos adversos , Neoplasias Pulmonares/virología , Linfoma de Células B/virología , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Antimetabolitos Antineoplásicos/efectos adversos , Antivirales/uso terapéutico , Niño , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células B/patología , Masculino , Mercaptopurina/efectos adversos , Metotrexato/efectos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND: The prophylactic use of hematopoietic growth factors has been shown to reduce the duration of neutropenia and related complications encountered after anticancer chemotherapy. However, the optimal timing for initiation of granulocyte colony-stimulating factor (G-CSF) has not been established. PROCEDURE: We evaluated the clinical parameters of the early versus delayed start (+1 day vs. +5 days postchemotherapy) of filgrastim (G-CSF; 5 micrograms/kg) after 36 courses of anticancer chemotherapy in 18 children with cancer in randomized fashion. Each child received two identical anticancer chemotherapeutic courses followed by one early (group 1) and one delayed (group 2) administration of G-CSF. Filgrastim was administered until absolute neutrophil count (ANC) exceeded 1.0 x 10(9)/l. RESULTS: The mean duration of G-CSF therapy was 8.6 (range, 5-14) days in group 1 and 5.4 (range, 3-10) days in group 2 (P = 0.001). The mean duration of neutropenia (ANC < 1.0 x 10(9)/l) did not differ between the study groups (7.8 vs. 8.2 days). Seven infection episodes occurred in group 1 and eight in group 2, respectively. The mean number of hospital days on broad-spectrum antibiotics was 2.3 (range, 0-8) in group 1 and 3.3 (range, 0-11) in group 2 (ns). CONCLUSIONS: We conclude that the delayed start of filgrastim reduced the costs of this treatment, but was not followed by more prolonged neutropenia or febrile neutropenias.
Asunto(s)
Antineoplásicos/efectos adversos , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Neoplasias/tratamiento farmacológico , Neutropenia/prevención & control , Adolescente , Infecciones Bacterianas/prevención & control , Niño , Preescolar , Análisis Costo-Beneficio , Femenino , Filgrastim , Factor Estimulante de Colonias de Granulocitos/economía , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Hospitalización/economía , Hospitalización/estadística & datos numéricos , Humanos , Lactante , Masculino , Estudios Prospectivos , Proteínas Recombinantes , Factores de TiempoRESUMEN
BACKGROUND: A cytogenetic study of 75 consecutive children with ALL revealed a normal karyotype, a low hyperdiploid karyotype (including 47-50 chromosomes), and a high hyperdiploid karyotype (including > 50 chromosomes) in 10, 12, and 33 patients, respectively. An acquired extra X-chromosome was detected at diagnosis by conventional cytogenetics in 29 (88%) of 33 children with a high hyperdiploid karyotype and in 4 (33%) of 12 children with a low hyperdiploid karyotype. X-chromosome aneuploidy was retrospectively studied by fluorescence in situ hybridization (FISH) in eight and 20 patients with a normal and a hyperdiploid karyotype, respectively. PROCEDURE: A classical cytogenetic study was performed according to standard methods. FISH with the centromeric probe specific to X-chromosome was used to study interphase cells of bone marrow or blood samples. RESULTS: An extra X-chromosome was found by FISH in all 13 patients with a high hyperdiploid or tetraploid, in 6 of 7 patients with a low hyperdiploid, and in none with a normal karyotype. Two children with a normal karyotype displayed monosomy X. Altogether, 57.3% of newly diagnosed children displayed X-chromosome aneuploidy. CONCLUSIONS: Out study indicates that X-chromosome aneuploidy may be the most common chromosome abnormality in childhood ALL. It can be detected in nearly all children with a high hyperdiploid karyotype and up to one-half of the patients with a low hyperdiploid karyotype. FISH with an X-chromosome centromeric probe is a rapid and simple tool to detect an abnormal clone at diagnosis in the majority of children with ALL and is useful in confirming remission in these patients.
Asunto(s)
Aneuploidia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Cromosoma X , Adolescente , Niño , Preescolar , Femenino , Humanos , Hibridación Fluorescente in Situ , Incidencia , Lactante , Cariotipificación , Masculino , Estudios RetrospectivosRESUMEN
BACKGROUND: The objective of this study was to assess the eligibility for and the course of compulsory military service of childhood cancer survivors. METHODS: The medical, military recruitment, conscription, and military service data of male Finnish childhood cancer survivors were collected from manually filed records. Inclusion criteria were: survivors born 1977 or earlier, treated for a malignancy between birth and age 15 years, and followed by a pediatrician until at least age 18 years. The documents of 207 survivors from the Pediatric Clinics of Finnish University Hospitals were examined, and 130 of these survivors were considered eligible for military service. Demographic factors, the predictors of fitness for military service, factors associated with service interruption, the attained level of military training, and the health status of conscripts during service were evaluated. Comparisons were made with the Finnish male population of the same age and with conscripts serving at the corresponding time. RESULTS: Approximately 60% of studied survivors were enlisted. Positive predictors of fitness for service were year of birth of 1973 or later (odds ratio [OR], 3.2), height at call-up age of 170-174.9 cm (OR, 3.6), and the man's own positive opinion of his fitness for service (OR, 62.3). Negative predictors were age at diagnosis > or = 11 years (OR, 0.5), central nervous system radiotherapy (OR, 0.3), limb defects (OR, 0.02), and the group of sequelae concerning neurologic, cardiopulmonary, and gastrointestinal systems, or secondary malignancies (OR, 0.3). Survivors interrupted their service more often (20%) (P < 0.001). Leukemia survivors were less likely to interrupt their service (7%) compared with other survivors (P = 0.04). Factors associated with service interruption were: diagnosis (P = 0.04), the man's own opinion of his fitness for service (P = 0.013), surgery (P = 0.003), and height (P = 0.049), weight (P = 0.019), and body mass index (P = 0.035) at the beginning of military service. The attained level of military training was equal to that of controls. The survivors visited the garrison physician less frequently in total (mean, 5.9 times) (P < 0.001), visited because of infections as much as controls, and were off duty more (mean, 11.9 days) (P = 0.012) than controls. CONCLUSIONS: The current study found that childhood cancer survivors were less likely to meet the requirements set for military service in Finland. The causes of rejection usually were obvious, but approximately 30% were rejected merely on the basis of a former cancer diagnosis. However, enlisted survivors coped well with military service if their treatment sequelae were taken into consideration carefully at the time of enlistment. Vocational opportunities within the armed forces might be an appropriate career option even for survivors of childhood malignancies.
Asunto(s)
Personal Militar/estadística & datos numéricos , Neoplasias/epidemiología , Sobrevivientes/estadística & datos numéricos , Adolescente , Adulto , Estatura , Peso Corporal , Niño , Preescolar , Escolaridad , Finlandia/epidemiología , Necesidades y Demandas de Servicios de Salud/estadística & datos numéricos , Humanos , Lactante , Masculino , Neoplasias/complicaciones , Neoplasias/fisiopatología , Aptitud FísicaRESUMEN
In a multinational, population-based study from the five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden), 2648 children below 15 y of age were diagnosed with acute lymphoblastic leukaemia (ALL) in the years 1981-1996. The annual incidence was 3.9/100000 children and was stable throughout the study period. The development from regional or national protocols to common Nordic treatment protocols for all risk groups was completed in 1992 through a successive intensification of therapy, based on multidrug chemotherapy including pulses of methotrexate in high doses and avoidance of cranial irradiation in most children. For children with non-B-cell ALL (n=2602), the event-free survival (p-EFS) increased from 0.53+/-0.02 (diagnosed 7/81-6/86) to 0.67+/-0.02 (7/86-12/91) to 0.78+/-0.02 (1/92-12/96). The corresponding p-EFS values at 5 y were 0.57, 0.70 and 0.78, respectively. The main improvements were seen in the group of children with non-high risk leukaemia, with 5-y p-EFS values increasing from 0.60 to 0.76 and 0.85 for the three periods. In high-risk patients, progress has been moderate, especially in children with high white blood cell values at diagnosis. During the last 5-y period, only 10% of the patients received cranial irradiation in first remission while 90% of the patients received high doses of cytostatic infusions (methotrexate isolated or combined with cytarabinoside) and multiple intrathecal injections of methotrexate as CNS-adjusted treatment without any indication of an increased CNS relapse rate.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Niño , Preescolar , Protocolos Clínicos , Femenino , Humanos , Lactante , Masculino , Probabilidad , Pronóstico , Estudios Retrospectivos , Países Escandinavos y Nórdicos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: We studied serum N-terminal atrial natriuretic peptide (NT-ANP) in children during and after chemotherapy for cancer to determine its applicability in detecting cardiac dysfunction. Forty-three patients were receiving chemotherapy for malignancy. Forty-eight patients were off chemotherapy and survived between 0.9 and 13 (median 5) years after the diagnosis, receiving cumulative anthracycline doses between 0 and 600 (median 225) mg/m2. PROCEDURE AND RESULTS: Cardiac evaluation of the patients included measurement of serum NT-ANP, recording of ECG, and assessment of systolic and diastolic function of the heart by echocardiography. During chemotherapy, serum NT-ANP levels were higher than in controls but varied markedly in the same individuals. Serum NT-ANP levels showed no consistent increase in the weeks following anthracycline administration. In late follow-up, serum NT-ANP levels were higher than in age-matched controls (median (range), 0.22 (0.06-0.47) vs. 0.14 (0.06-0.27) nmol/l, respectively, P < .001). The subgroup of patients with bone marrow transplantation and/or cardiac irradiation had the highest NT-ANP concentrations (0.30 (0.20-0.45) nmol/l). CONCLUSIONS: Thus, serum NT-ANP measurements seemed to represent a useful contribution in the long-term cardiac follow-up of children after cancer. This blood test can readily be included to laboratory follow-up, is reasonably inexpensive and may decrease the need for more laborious tests of cardiac function. When there is ongoing chemotherapy, NT-ANP levels are influenced by a variety of factors that invalidate its routine use during this period.
Asunto(s)
Antibióticos Antineoplásicos/efectos adversos , Factor Natriurético Atrial/sangre , Sistema Cardiovascular/efectos de los fármacos , Daunorrubicina/efectos adversos , Doxorrubicina/efectos adversos , Adolescente , Sistema Cardiovascular/diagnóstico por imagen , Sistema Cardiovascular/fisiopatología , Niño , Preescolar , Ecocardiografía , Electrocardiografía , Femenino , Humanos , Lactante , Masculino , Valor Predictivo de las PruebasRESUMEN
In a retrospective analysis we evaluated the occurrence of infections in 59 children with acute lymphoblastic leukemia (ALL) during the entire duration of their anticancer chemotherapy. We recorded a total of 245 infection episodes, 118 (50%) being during neutropenia and 119 (50%) during nonneutropenia. The infections most commonly detected during neutropenia were fevers of undetermined origin (36%), clinically or microbiologically defined focal infections (33%), and bacteremias (28%). During nonneutropenia, upper respiratory tract infections (55%) were the most common. Patients needed hospitalization for infections for a total of 1951 days (i.e., a mean of 33 days per patient) and the mean number of infection episodes was 4.2 per patient. Recurrent fever developed in 21% of the children with bacteremia. Mortality caused by bacteremias was 10%. Infections during the chemotherapy of ALL were a significant cause of morbidity in children, but mortality was low.
Asunto(s)
Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Infecciones Bacterianas/inducido químicamente , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Bacteriemia/etiología , Niño , Preescolar , Femenino , Fiebre de Origen Desconocido/etiología , Infección Focal/microbiología , Hospitalización , Humanos , Lactante , Masculino , Neutropenia/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Recurrencia , Infecciones del Sistema Respiratorio/inducido químicamente , Estudios Retrospectivos , Virosis/etiologíaRESUMEN
UNLABELLED: Eighty-two children with malignant brain tumours were treated according to the "8 in 1" chemotherapy protocol in Finland during 1986 to 1993. Thirty-seven with brain tumours not involving the hypothalamic-pituitary region are still alive and tumour-free. The growth and response to growth hormone (GH) therapy in these children was analysed. Children who received craniospinal irradiation had the most severe loss of height SDS, being -1.07 within 3 years of the diagnosis. Even children with no irradiation to the hypothalamic-pituitary axis had a mean change in height SDS of -0.5 after 3 years. Fifteen of 23 children who received craniospinal irradiation and two out of eight children who received cranial irradiation have received GH therapy. A catch-up growth response to the daily GH therapy with the mean dose of 0.7 IU/kg per week was complete in 3 years (+1.87 SDS), irrespective of craniospinal irradiation, in children who were treated at prepubertal age but was seen in none of the children who had reached pubertal age. CONCLUSION: Growth impairment and GH deficiency are common in children treated for malignant brain tumours. The response to GH therapy is good in prepubertal children in terms of increased growth velocity, although the final height is not yet known.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Encefálicas/tratamiento farmacológico , Enanismo/terapia , Hormona de Crecimiento Humana/administración & dosificación , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estatura/efectos de los fármacos , Neoplasias Encefálicas/radioterapia , Niño , Preescolar , Terapia Combinada , Irradiación Craneana , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Enanismo/etiología , Femenino , Humanos , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/efectos de la radiación , Lactante , Masculino , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/efectos de la radiación , Radioterapia AdyuvanteRESUMEN
Sixty-four children with malignant brain tumours diagnosed at less than 3 years of age were reported to the Finnish Cancer Registry from 1975 to 1993. The survival rate has improved significantly: the 5-year survival rate was 26% for all children, 13% for children diagnosed during 1975-85 (n = 30) and 40% for those diagnosed during 1986-93 (n = 34). Of the surviving children in 1986-93, 43% were categorized in Bloom's group I or II and could lead active lives without major disabilities. The remaining children had severe neurologic late complications, such as hemiplegia, intractable seizures, and mental retardation.
Asunto(s)
Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/terapia , Factores de Edad , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/fisiopatología , Preescolar , Cognición/fisiología , Terapia Combinada , Supervivencia sin Enfermedad , Estudios de Evaluación como Asunto , Femenino , Finlandia/epidemiología , Humanos , Lactante , Masculino , Destreza Motora/fisiología , Complicaciones Posoperatorias , Pronóstico , Calidad de Vida , Sistema de Registros , Tasa de SupervivenciaRESUMEN
A 2-year-old boy with acute lymphoblastic leukemia initially experienced pericardial effusion during the maintenance treatment due to leukemic infiltration of the pericardium and cardiac muscle. He subsequently died suddenly owing to leukemic occlusion of the left coronary artery.
Asunto(s)
Enfermedad Coronaria/etiología , Derrame Pericárdico/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Preescolar , Enfermedad Coronaria/patología , Resultado Fatal , Humanos , MasculinoRESUMEN
PURPOSE: To evaluate the following prospectively in poor-risk neuroblastoma (NBL) patients: (1) the feasibility and efficacy of in vivo purging of bone marrow; and (2) the outcome after autologous bone marrow transplantation (ABMT) when immunologically tumor-free, unpurged autografts were used. PATIENTS AND METHODS: Twenty-three children with poor-risk NBL were evaluated during induction chemotherapy by repeat bone marrow examinations, including aspirate, biopsy, and an immunofluorescence method using the anti-GD2 monoclonal antibody 3A7. Nineteen patients completed the program with surgery with or without local irradiation followed by ABMT. RESULTS: Autologous bone marrow grafts, both immunologically and cytologically clean, were obtained and used in 19 of 23 children. The overall 4-year disease-free survival of the 19 grafted children was 53%, with a toxic death rate of 16% and a posttransplant relapse rate of 37%. According to the in vivo purging efficacy of the 18 children with initial marrow disease, the following three groups were formed: patients with (1) perfect in vivo purging (n = 5); (2) eventually successful in vivo purging (n = 8); and (3) unsuccesful in vivo purging (n = 5). The 4-year DFS was 100%, 67%, and 0%, respectively (P < 0.001). The five patients with unsuccessful in vivo purging failed because of resistant/progressive bulky disease. CONCLUSION: In patients with poor-risk NBL, in vivo purging of bone marrow by conventional chemotherapy is feasible, can be monitored, and the purging efficacy during the first 3 months after diagnosis is a strong prognostic factor reflecting tumor responsiveness to therapy. Autografting with immunologically clean, unpurged marrows gives a DFS well comparable to previous studies using ex vivo purging.
Asunto(s)
Examen de la Médula Ósea , Purgación de la Médula Ósea/métodos , Trasplante de Médula Ósea , Neuroblastoma/terapia , Acondicionamiento Pretrasplante , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Médula Ósea/patología , Niño , Preescolar , Resistencia a Antineoplásicos , Estudios de Factibilidad , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Supervivencia de Injerto , Humanos , Lactante , Masculino , Neuroblastoma/patología , Estudios Prospectivos , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
BACKGROUND: Adjuvant chemotherapy has improved the outcome of childhood malignant brain tumors in large randomized trials. With increasing survival rates, treatment toxicity has become a matter of concern. Radiation therapy and cisplatinum are known to be ototoxic. METHODS: We evaluated the incidence and factors predisposing to ototoxicity in children treated with the "8 in 1" chemotherapy protocol in Finland during 1986--1993. Thirty-five of the 82 children survived for at least 1 year after diagnosis. Thirty of these children were old enough to have an audiogram. RESULTS: Seventeen of the 30 children had normal hearing, seven had hearing loss at high frequencies, and six (20%) had severe hearing loss in the speech range. The risk factors for severe hearing loss were young age, a high cumulative dose of cisplatinum, and deteriorating renal function. In the presence of these factors, the risk of severe hearing loss was over 50%. Hearing loss at high frequencies could occur after low cumulative doses of cisplatinum, but severe hearing loss correlated with high cumulative doses. CONCLUSIONS: Cisplatinum-induced hearing loss at high frequencies is common, but hearing loss in the speech range also occurs, particularly in children with predisposing factors, and may progress insidiously and rapidly. Therefore a hearing test before each "8 in 1" course is important.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Pérdida Auditiva/etiología , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/complicaciones , Quimioterapia Adyuvante , Niño , Preescolar , Cisplatino/administración & dosificación , Terapia Combinada , Ciclofosfamida/administración & dosificación , Citarabina/administración & dosificación , Dacarbazina/administración & dosificación , Esquema de Medicación , Estudios de Evaluación como Asunto , Femenino , Estudios de Seguimiento , Pérdida Auditiva/inducido químicamente , Pérdida Auditiva/epidemiología , Humanos , Hidroxiurea/administración & dosificación , Incidencia , Lactante , Lomustina/administración & dosificación , Masculino , Metilprednisolona/administración & dosificación , Procarbazina/administración & dosificación , Traumatismos por Radiación/epidemiología , Traumatismos por Radiación/etiología , Factores de Riesgo , Vincristina/administración & dosificaciónRESUMEN
Sixty-eight children with malignant brain tumors were treated with the "8 in 1" chemotherapy protocol from 1986 to 1993 in Finland. The overall 5-year survival rate was 43%. Thirty-one children are still alive and tumor-free, and have been evaluated in the present study. Of these 31 children, 26% had hemi- or tetraplegia, 13% intractable seizures, and 30% attend special schools. The mean full scale (FS) IQ was 85 (range 45-138), 24% had an FSIQ value less than 70, and 36% more than 90. One-half of the survivors were placed in Bloom's group I or II, are able to lead an active life, and have only mild neurologic disabilities. In the other, neurologic late complications accumulated and these children were relegated to Bloom's group III or IV, with major disabilities such as hemiplegia, intractable epilepsy, or mental retardation. The most important prognostic factors were severe perioperative complications, young age at diagnosis, and cranial irradiation.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Daño Encefálico Crónico/etiología , Neoplasias Encefálicas/cirugía , Irradiación Craneana/efectos adversos , Craneotomía/efectos adversos , Pruebas Neuropsicológicas , Complicaciones Posoperatorias/etiología , Adolescente , Daño Encefálico Crónico/diagnóstico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Quimioterapia Adyuvante , Niño , Preescolar , Terapia Combinada , Evaluación de la Discapacidad , Educación Especial , Femenino , Humanos , Lactante , Inteligencia/efectos de los fármacos , Inteligencia/efectos de la radiación , Discapacidades para el Aprendizaje/diagnóstico , Discapacidades para el Aprendizaje/etiología , Masculino , Examen Neurológico/efectos de los fármacos , Examen Neurológico/efectos de la radiación , Complicaciones Posoperatorias/diagnóstico , Dosificación Radioterapéutica , Radioterapia AdyuvanteRESUMEN
We evaluated the outcome of 68 children with malignant brain tumors treated with the "8 in 1" chemotherapy protocol in Finland from 1986 to 1993, comparing 5-year survival rates with those for a historical control group (from 1975 to 1985). For all malignant brain tumors, overall survival was 43% (vs 28% in the control group; P <0.05), and progression-free survival (PFS) was 43% (vs 23%; P <0.05). For medulloblastoma and primitive neuroectodermal tumor, survival was 63% (vs 35%; P <0.05), and the corresponding PFS was 59% (vs 35%; P = 0.15). For high-grade glioma, both the survival rate and the PFS were 27% (vs 17%; P = NS). Thus the outcome was significantly better for our "8 in 1" -treated patients than for the historical controls, especially among the children with primitive neuroectodermal tumor and medulloblastoma. In contrast, those with high-grade gliomas and brain stem tumors seem to have received little benefit; different, more effective treatments are needed for these patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Adolescente , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/radioterapia , Niño , Preescolar , Femenino , Finlandia , Glioma/tratamiento farmacológico , Humanos , Lactante , Masculino , Meduloblastoma/tratamiento farmacológico , Tasa de SupervivenciaRESUMEN
PURPOSE: The comparable health-care organizations and common Cancer Registry for childhood malignancies in the five Nordic countries offered an opportunity to conduct an epidemiological study on a reasonable number of childhood non-Hodgkin's lymphoma (NHL) cases collected in a population-based manner. MATERIAL AND METHODS: All childhood cases (0-14.9 years at diagnosis) reported during the 5-year period of 1985-1989 to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) Cancer Registry for childhood malignancies were reviewed and analyzed according to age, Murphy's stage, gender, site, and survival. RESULTS: The annual incidence of NHL is 0.7 per 100,000 children in the five Nordic countries, constituting 5% of all childhood malignancies. Age distribution was even; the male/female ratio was 3:1. Age and stage were shown by Cox regression analysis to be independent prognostic factors. Older age and lower stage affected outcome favorably. The stage and site distribution was similar to previous reports. Survival data were in accordance with those expected with modern treatment protocols. CONCLUSIONS: The incidence and relative frequency of NHL in childhood in the five Nordic countries is in agreement with previously reported data, but the even distribution of cases throughout childhood is a new finding. Older age at onset and stage of disease affect outcome favorably, whereas male gender contrary to acute lymphoblastic leukemia was not found to affect outcome.