RESUMEN
BACKGROUND: There are no published reference intervals for concentrations of alpha-fetoprotein (AFP) in the cerebrospinal fluid (CSF) of normal infants. The presence of abnormal concentrations of AFP in plasma or CSF may indicate the presence of a teratoma or a germ cell tumour with yolk sac elements. We measured CSF AFP in infants who did not have malignancy in order to determine its reference intervals. METHODS: AFP was measured in the CSF and/or plasma in 128 infants. Of these, 91 infants had CSF AFP measurements, 94 infants had plasma AFP measurements and in 60 infants AFP concentrations were determined in paired CSF and plasma samples. The patients ranged in age from 1 to 110 days. Both CSF and plasma AFP concentrations were measured by a microparticle enzyme immunoassay using an AxSYM analyser. RESULTS: Using ages corrected for prematurity, the median CSF AFP concentration for babies -69 to 31 days old was 61 kIU/L (5th-95th centile: 2-889 kIU/L), while the median CSF AFP concentration for infants 32 to 110 days was 1.2 kIU/L (5th-95th centile: 0.1-12.5 kIU/L). By age 6 weeks, the concentrations were close to those found in adult plasma and all CSF AFP concentrations from infants with a corrected age over 2 months were <3 kIU/L. CONCLUSION: We have defined reference intervals for CSF AFP concentrations in infants. These results may assist in the diagnosis of CNS tumours, particularly congenital CNS tumours containing yolk sac elements.
Asunto(s)
alfa-Fetoproteínas/líquido cefalorraquídeo , Ensayo de Inmunoadsorción Enzimática , Edad Gestacional , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Masculino , Valores de Referencia , alfa-Fetoproteínas/metabolismoRESUMEN
This study evaluated the quality of life and neuropsychologic functioning among patients enrolled between 1989 and 1993 in the First International CNS Germ-Cell Tumor Study. Quality-of-life questionnaires (Short Form-36 or Child Health Questionnaire) were completed on 43 patients at median follow-up of 6.1 years after diagnosis (range, 4.5-8.8 years), and intellectual and academic testing was performed on 22 patients. Psychosocial and physical functioning of patients aged 19 years and older at follow-up was within the average range, whereas the same functioning for patients aged 18 years and younger, as reported by their parents at follow-up, was low average and borderline, respectively. Overall psychosocial and physical health summary scores were positively correlated with age at diagnosis for both groups combined. Those who received CNS radiation therapy (n = 29) reported significantly worse physical health, but similar psychosocial health, compared with those treated without radiation. Neuropsychologic testing indicated full-scale and verbal IQ, reading, spelling, and math skills in the average range, and performance IQ in the low average range. Intelligence and math skills were positively correlated with age at diagnosis. Those with germinomas significantly outperformed those with nongerminomatous/ mixed tumors on all neuropsychological measures administered. Younger patients diagnosed with CNS germ-cell tumors are at increased risk for psychosocial and physical problems as well as neuropsychologic deficits. Exposure to irradiation adversely affects overall physical functioning, whereas tumor pathology appears to be a salient neurocognitive risk factor. Collaborative and randomized studies are required to further elucidate the late effects arising from factors such as age at diagnosis, tumor histology, level of irradiation therapy, and chemotherapy toxicity among these young and potentially curable patients.
Asunto(s)
Neoplasias del Sistema Nervioso Central/psicología , Inteligencia , Neoplasias de Células Germinales y Embrionarias/psicología , Calidad de Vida , Adolescente , Adulto , Anciano , Neoplasias del Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/radioterapia , Niño , Trastornos del Conocimiento/etiología , Femenino , Estudios de Seguimiento , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias de Células Germinales y Embrionarias/radioterapia , Pruebas Neuropsicológicas , Radioterapia/efectos adversosRESUMEN
PURPOSE: This study was designed to determine the feasibility and safety of delivering four consecutive cycles of high-dose cyclophosphamide, cisplatin, and vincristine, each followed by stem-cell rescue, every 4 weeks, after completion of risk-adapted craniospinal irradiation to children with newly diagnosed medulloblastoma or supratentorial primitive neuroectodermal tumor (PNET). PATIENTS AND METHODS: Fifty-three patients, 19 with high-risk disease and 34 with average-risk disease, were enrolled onto this study. After surgical resection, high-risk patients were treated with topotecan in a 6-week phase II window followed by craniospinal radiation therapy and four cycles of high-dose cyclophosphamide (4,000 mg/m2 per cycle), with cisplatin (75 mg/m2 per cycle), and vincristine (two 1.5-mg/m2 doses per cycle). Support with peripheral blood stem cells or bone marrow and with granulocyte colony-stimulating factor was administered after each cycle of high-dose chemotherapy. Treatment of average-risk patients consisted of surgical resection and craniospinal irradiation, followed by the same chemotherapy given to patients with high-risk disease. The expected duration of the chemotherapy was 16 weeks, with a cumulative cyclophosphamide dose of 16,000 mg/m2 and a planned dose-intensity of 1,000 mg/m2/wk. RESULTS: Fifty of the 53 patients commenced high-dose chemotherapy, and 49 patients completed all four cycles. The median length of chemotherapy cycles one through four was 28, 27, 29, and 28 days, respectively. Engraftment occurred at a median of 14 to 15 days after infusion of stem cells or autologous bone marrow. The intended dose-intensity of cyclophosphamide was 1,000 mg/m2/wk; the median delivered dose-intensity was 1,014, 1,023, 974, and 991 mg/m2/wk for cycles 1 through 4, respectively; associated median relative dose-intensity was 101%, 102%, 97%, and 99%. No deaths were attributable to the toxic effects of high-dose chemotherapy. Early outcome analysis indicates a 2-year progression-free survival of 93.6% +/- 4.7% for the average-risk patients. For the high-risk patients, the 2-year progression-free survival is 73.7% +/- 10.5% from the start of therapy and 84.2% +/- 8.6% from the start of radiation therapy. CONCLUSION: Administering four consecutive cycles of high-dose chemotherapy with stem-cell support after surgical resection and craniospinal irradiation is feasible in newly diagnosed patients with medulloblastoma/supratentorial PNET with aggressive supportive care. The early outcome results of this approach are very encouraging.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Meduloblastoma/tratamiento farmacológico , Tumores Neuroectodérmicos Primitivos/tratamiento farmacológico , Adolescente , Adulto , Transfusión Sanguínea , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirugía , Niño , Preescolar , Cisplatino/administración & dosificación , Terapia Combinada , Ciclofosfamida/administración & dosificación , Estudios de Factibilidad , Femenino , Humanos , Masculino , Meduloblastoma/radioterapia , Meduloblastoma/cirugía , Tumores Neuroectodérmicos Primitivos/radioterapia , Tumores Neuroectodérmicos Primitivos/cirugía , Células Madre/efectos de los fármacos , Topotecan/administración & dosificación , Vincristina/administración & dosificaciónRESUMEN
The development of curative strategies for infants and children with central nervous system tumours or acute lymphoblastic leukaemia involve similar clinical research principles. Both areas of paediatric oncology research focus on cancers with a broad range of sensitivity to chemotherapy and radiation therapy, together with concerns about the neurodevelopmental, neuroendocrine and growth outcomes of survivors. These considerations have influenced the design of curative- intent treatments, strategies for successfully eradicating leptomeningeal disease, and the importance of anatomic and functional identification of residual disease. Unlike the situation with childhood leukaemia, the emotional barriers of pessimism or even nihilism previously evident towards infants with brain tumours have only begun to crumble during the past decade. The challenge to improve both the quality and overall survival of infants with CNS tumours described in this chapter is ours to meet as we move into the new millennium. This paper examines the development of 'infant' approaches to the treatment of CNS tumours, including a discussion of epidemiology, the reasons for avoiding or delaying radiation therapy, and traces the chemotherapy hypotheses tested over the past two decades in the process of developing potentially curative therapy. The reasons for the disappointing rate of progress compared with that in childhood leukaemia, despite similar clinical research paradigms, are discussed, and potential opportunities are identified.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Antineoplásicos/efectos adversos , Neoplasias Encefálicas/epidemiología , Neoplasias Encefálicas/radioterapia , Preescolar , Humanos , Incidencia , Lactante , Modelos TeóricosAsunto(s)
Vincristina/uso terapéutico , Adolescente , Adulto , Niño , Preescolar , Humanos , Neoplasias/tratamiento farmacológicoRESUMEN
Bone scintigraphy is not performed routinely in the diagnostic work-up of children with leukemia; however, the initial diagnosis of childhood leukemia is often difficult to make and may be delayed. Patients may present with fever and skeletal symptoms and, in such cases, bone scintigraphy may be requested in the early search for a diagnosis. Recognition of the potential scintigraphic abnormalities that result from leukemic infiltration of bone and bone marrow will often facilitate an early diagnosis of leukemia. Bone scans also play a role in detecting osteomyelitis in the immunosuppressed leukemic child with fever and bone pain. This article presents four patients illustrating the salient features of bone scintigraphy in these clinical settings.
Asunto(s)
Huesos/diagnóstico por imagen , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico por imagen , Artritis Infecciosa/diagnóstico por imagen , Huesos/patología , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Humanos , Infiltración Leucémica , Masculino , Osteomielitis/diagnóstico por imagen , CintigrafíaAsunto(s)
Radioisótopos de Talio , Timo/diagnóstico por imagen , Timo/patología , Tomografía Computarizada de Emisión de Fotón Único , Niño , Femenino , Humanos , Hiperplasia/metabolismo , Linfoma de Células B/terapia , Imagen por Resonancia Magnética , Radioisótopos de Talio/metabolismo , Timo/metabolismo , Tomografía Computarizada de Emisión de Fotón Único/métodos , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: We evaluated the clinical efficacy of preirradiation carboplatin (CARBO) and etoposide (VP-16) in 25 patients with newly diagnosed embryonal CNS tumors. PATIENTS AND METHODS: Sixteen patients with high-risk medulloblastoma and nine with other embryonal tumors were treated with two daily doses of CARBO 350 mg/m2 and VP-16 100 mg/m2 (CARBO/VP) every 21 days for four cycles before standard craniospinal irradiation. Patients with disease progression (PD) before radiation therapy were additionally treated with intensive postirradiation cyclophosphamide (CYCLO) and vincristine (VINC). RESULTS: Among 23 assessable patients, 48% (95% confidence interval, 27% to 69%) had a complete response (CR) or partial response (PR) to CARBO/VP; eight had PD. Among the subgroup of 15 assessable patients with medulloblastoma, 53% had a CR or PR (95% confidence interval, 27% to 79%) and five PD. The toxicity of CARBO/VP was predominantly hematologic; although grade IV neutropenia was common, only five episodes of febrile neutropenia occurred. Only thrombocytopenia was a more common toxicity than in other reported chemotherapy regimens; ototoxicity was less common than in cisplatin (CDDP) regimens. CONCLUSION: The responses and survival associated with neoadjuvant CARBO/VP are similar to those with CDDP-containing and other neoadjuvant drug regimens. Although the rate of progression with this regimen may be higher than with similar CDDP-containing regimens, the numbers of patients in other published studies of these agents are too small to detect meaningful statistical differences. Future studies must balance the apparently comparable efficacy of CARBO and CDDP with their differing toxicities.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Neoplasias del Sistema Nervioso Central/mortalidad , Neoplasias del Sistema Nervioso Central/radioterapia , Niño , Preescolar , Terapia Combinada , Irradiación Craneana , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Humanos , Masculino , Meduloblastoma/tratamiento farmacológico , Meduloblastoma/radioterapia , Neoplasias de Células Germinales y Embrionarias/mortalidad , Neoplasias de Células Germinales y Embrionarias/radioterapia , Neutropenia/inducido químicamente , Inducción de Remisión , Tasa de Supervivencia , Trombocitopenia/inducido químicamente , Vincristina/administración & dosificaciónRESUMEN
A 3.5-yr-old child presented with a large thoracic mass which showed avid accumulation of 67Ga and 201Tl was studied. Histology showed a peripheral neuroectodermal tumor of the chest wall typical of the malignancy described as the Askin tumor. The 201Tl studies were a more accurate method of following tumor response to therapy than 67Ga scintigraphy.
Asunto(s)
Radioisótopos de Galio , Tumores Neuroectodérmicos Primitivos/diagnóstico por imagen , Sarcoma de Células Pequeñas/diagnóstico por imagen , Radioisótopos de Talio , Neoplasias Torácicas/diagnóstico por imagen , Preescolar , Diagnóstico Diferencial , Humanos , Masculino , Radiografía , CintigrafíaRESUMEN
PURPOSE: To report the impact of bone marrow transplantation (BMT) with busulfan/cyclophosphamide (BuCy) as end consolidation in a cohort of consecutively diagnosed children with acute myeloid leukemia (AML). PATIENTS AND METHODS: Between May 1987 and November 1992, 43 patients were diagnosed with AML. Tissue typing at diagnosis determined whether patients would proceed to autologous or allogeneic BMT as end consolidation after six cycles of chemotherapy. Conditioning for BMT was with BuCy, followed by allogeneic or unpurged autologous marrow infusion. RESULTS: Of 37 patients who received chemotherapy, 35 achieved remission (95%) after one to six courses of treatment and 34 (92%) were transplanted. Five relapsed before BMT, four were subsequently transplanted in second complete remission (CR2) (n = 3) or untreated first relapse (n = 1), and one failed to respond to further therapy. All other patients proceeded to BMT in first complete remission (CR1). Eleven patients received allografts: one relapsed and one died of graft-versus-host disease (GvHD), for a leukemia-free survival rate of 90% at a median of 41 months after BMT (range, 3 to 60). For 23 autografts, there were two toxic deaths and eight relapses, with a leukemia-free survival rate of 61% at a median of 11 months after BMT (range, 0 to 66). The high relapse rate following autologous BMT led us to escalate the dose of Bu from 16 mg/kg to 600 mg/m2 using a single daily dose of Bu. CONCLUSION: With modern supportive therapy, most newly diagnosed children with AML will enter remission and are eligible for intensification therapy. BuCy is well tolerated in children, which allowed us to escalate the dose of Bu in recent patients. Further follow-up is needed to determine whether this has an impact on the relapse rate following autologous BMT.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea , Leucemia Mieloide Aguda/terapia , Adolescente , Busulfano/administración & dosificación , Niño , Preescolar , Estudios de Cohortes , Terapia Combinada , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Lactante , Leucemia Mieloide Aguda/tratamiento farmacológico , Masculino , Pronóstico , Inducción de RemisiónRESUMEN
BACKGROUND: Ifosfamide with Mesna, given every other day over a 5-day period, was evaluated in 20 children with recurrent or progressive primary brain tumors. METHODS: The patients were assigned to dosage cohorts separated on the basis of prior exposure to cisplatin (n = 10) or the absence of such exposure (n = 10). The initial dose in each treatment arm was 2133 mg/m2 every other day for three doses, which represented 80% of the total dose delivered in our prior study of ifosfamide given daily over 5 days. The dose was escalated by 20% in each of the two subsequent cohorts (2560 mg/m2 and 3072 mg/m2 every other day for three doses). RESULTS: The hematologic toxicity was dose limiting. Prior exposure to cisplatin did not seem to increase the hematologic toxicity. The most frequent and significant metabolic disturbance was hyponatremia, resulting in self-limited seizure activity in three patients. This complication was prevented in subsequent patients by changing the post-ifosfamide hydration fluids from 5% dextrose in quarter normal saline to 5% dextrose in normal saline. CONCLUSIONS: Although no child achieved a complete response, the activity of ifosfamide was demonstrated for a variety of tumors. The recommended dose of ifosfamide in a Phase II study for brain tumors is 3000 mg/m2 given with Mesna every other day for three doses.
Asunto(s)
Neoplasias Encefálicas/tratamiento farmacológico , Ifosfamida/administración & dosificación , Adolescente , Neoplasias Encefálicas/sangre , Niño , Preescolar , Cisplatino/administración & dosificación , Esquema de Medicación , Femenino , Fluidoterapia , Humanos , Hiponatremia/inducido químicamente , Hiponatremia/complicaciones , Ifosfamida/efectos adversos , Recuento de Leucocitos/efectos de los fármacos , Masculino , Mesna/administración & dosificación , Convulsiones/etiología , Convulsiones/prevención & controlAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Trasplante de Médula Ósea , Neoplasias Óseas , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/cirugía , Niño , Terapia Combinada , Humanos , Masculino , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/secundario , Osteosarcoma/cirugíaRESUMEN
Of 29 consecutive children treated for malignant primary tumors of the central nervous system (CNS) at this institution, postoperative examination showed radiographic or cytologic evidence of neuraxis dissemination in 10 (34%). Given the historically poor results in disseminated CNS tumors treated with surgery and radiation therapy alone, these ten patients were treated prospectively with an investigational Phase II protocol consisting of preirradiation cisplatin (90 mg/m2 on day 1) and etoposide (150 mg/m2 on days 3 and 4). The diagnoses included medulloblastoma (n = 4), malignant glioma (n = 3), cerebral primitive neuroectodermal tumor (n = 1), pineoblastoma (n = 1), and mixed glioma of the brainstem (n = 1). Postoperative neuraxis scanning with computed tomography, magnetic resonance imaging, or spinal myelography showed measurable intracranial or spinal metastases in all children. The cerebrospinal fluid (CSF) cytologic examination was positive for tumor cells in five. The best responses, based on serial imaging of neuraxis metastases, included two complete responses, four partial responses, and three stable disease states. One patient had progressive disease at the primary site despite stable disease in the spine; progressive neuraxis disease was documented in only one patient during chemotherapy. Clearance of tumor cells from the CSF was documented in three patients. The adverse effects of chemotherapy, consisting of transient myelosuppression and mild ototoxicity, were minimal. Reversible neurologic deterioration occurred in two patients; one patient became acutely quadriplegic after a prolonged convulsive seizure without radiographic evidence of tumor progression.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Nervioso Central/secundario , Adolescente , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/radioterapia , Niño , Preescolar , Cisplatino/administración & dosificación , Terapia Combinada , Evaluación de Medicamentos , Etopósido/administración & dosificación , Humanos , Imagen por Resonancia Magnética , Mielografía , Estadificación de NeoplasiasRESUMEN
To evaluate the anticancer agent flavone acetic acid (FAA), we conducted a Phase I trial involving 17 pediatric patients with various malignant solid tumors. Dosages investigated included 5,120 and 6,144 mg/m2 given as 3-hour intravenous infusions; and 10,000, 12,500, 15,000, and 17,500 mg/m2 delivered in a 24-hour constant infusion with alkalinization. Grade 2 or worse toxicity was minimal, with 2 patients having nausea/vomiting, 2 having diarrhea, 1 becoming hypertensive, 1 becoming hypotensive, and 2 having myalgia. Three patients who received a 17,500 mg/m2 dose had no toxicity. Disease was stabilized for a brief period in 2 patients--1 with brain stem glioma and 1 with astrocytoma. The FAA pharmacokinetics varied with an average (SD) terminal half-life of 27.9 hr (18.7), clearance of 2.04 L/hr/m2 (0.37), and steady-state volume of 19.9 L/m2 (10.6). This study was discontinued because FAA caused no significant toxicity or therapeutic responses at doses 2.5 gm/m2 greater than had been tolerated by adults.
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Antineoplásicos/uso terapéutico , Flavonoides/uso terapéutico , Neoplasias/tratamiento farmacológico , Adolescente , Adulto , Antineoplásicos/efectos adversos , Antineoplásicos/farmacocinética , Niño , Preescolar , Evaluación de Medicamentos , Femenino , Flavonoides/efectos adversos , Flavonoides/farmacocinética , Humanos , Análisis de los Mínimos Cuadrados , MasculinoRESUMEN
The authors report the clinicopathologic and neuroimaging findings in ten children with primary abdominal or thoracic neuroblastoma who relapsed in the central nervous system (CNS) without evidence of concurrent intracranial extension from adjacent bone, dura, or dural sinus metastases. At diagnosis, the patients ranged in age from 0.3 to 4.5 years (median, 2 years). Their times to CNS relapse ranged from 2 to 34 months from diagnosis. In seven patients the relapse occurred from 1 to 14 months after elective discontinuation of therapy. In four patients, the CNS relapse was the primary (isolated) adverse event. Four patients could not be treated at the time of relapse, and they died within 7 days of progressive CNS disease. In the remaining group, craniospinal irradiation with or without administration of a platinum compound and an epipodophyllotoxin caused complete CNS remissions lasting 4, 5, 16, and 62+ months. Neuroimaging and autopsy findings indicated that cerebrospinal fluid is the major pathway for neuraxis dissemination by neuroblastoma cells. There was no evidence of dural penetration in any patient. The possibility of relapse in the neuraxis should be considered for any patient with neuroblastoma who had neurologic deterioration. A combination of craniospinal radiation and administration of a platinum compound and an epipodophyllotoxin will induce complete responses in some patients with neuraxis involvement by neuroblastoma, but the risk of subsequent failure outside the CNS remains high.
Asunto(s)
Neoplasias Abdominales , Neoplasias del Sistema Nervioso Central/secundario , Neuroblastoma/secundario , Neoplasias Torácicas , Neoplasias Abdominales/patología , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias del Sistema Nervioso Central/diagnóstico por imagen , Neoplasias del Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/terapia , Preescolar , Terapia Combinada , Irradiación Craneana , Diagnóstico por Imagen , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Recurrencia Local de Neoplasia , Neuroblastoma/diagnóstico por imagen , Neuroblastoma/patología , Neuroblastoma/terapia , Inducción de Remisión , Neoplasias Torácicas/patología , Tomografía Computarizada por Rayos XRESUMEN
The incidence, clinical characteristics, and outcome of hypersensitivity reactions to teniposide (VM-26), etoposide (VP-16), or both were determined in 108 children with acute lymphoblastic leukemia (ALL) treated with a contemporary regimen of intensive multiagent chemotherapy. Fifty (46%) of the 108 patients had one or more hypersensitivity reactions. The risk of any child having an initial reaction over the cumulative dose range studied was 52% (95% confidence limits, 41% and 63%) for VM-26, compared with 34% (95% confidence limits, 24% and 44%) for VP-16. The risk of having an initial reaction to VM-26 or VP-16 was clearly related to the cumulative dose. This risk peaked at 1500 to 2000 mg/m2 for VM-26 and at 2000-3000 mg/m2 for VP-16. All reactions were Type 1 reactions according to the Gell and Coombs classification, characterized by urticaria, angioedema, flushing, rashes, or hypotension, and 86% of reactions were of Grade 1 or 2 severity according to standard criteria. There was no evidence of increasing clinical severity on repeated rechallenge with premedication, and no deaths occurred. The findings suggested that hypersensitivity reactions to epipodophyllotoxins in children with ALL are more common than previously reported, but only rarely constitute dose-limiting toxicity.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Hipersensibilidad a las Drogas/etiología , Etopósido/efectos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Tenipósido/efectos adversos , Adolescente , Corticoesteroides/uso terapéutico , Espasmo Bronquial/inducido químicamente , Niño , Preescolar , Cianosis/inducido químicamente , Difenhidramina/uso terapéutico , Relación Dosis-Respuesta a Droga , Hipersensibilidad a las Drogas/prevención & control , Etopósido/administración & dosificación , Femenino , Humanos , Hipotensión/inducido químicamente , Lactante , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Premedicación , Tenipósido/administración & dosificaciónRESUMEN
Medulloblastoma, pineoblastoma, and cerebral neuroblastoma are malignant embryonal tumors of the CNS that may demonstrate similar histologic features, a propensity for neuraxis dissemination and sensitivity to radiation therapy and, in certain cases, chemotherapy. To evaluate the activity of preirradiation chemotherapy in such tumors, 11 newly diagnosed children with measurable residual disease and characteristics indicative of poor prognosis were treated postoperatively with cisplatin (CDDP) and etoposide (VP-16). Responses graded on the basis of radiographic findings in areas of either macroscopic residual tumor or metastatic disease included two complete responses (CRs), eight partial responses (PRs), and one stable disease (SD). Acute and subacute toxicity consisted of high-frequency hearing loss in four patients, reversible signs and symptoms of increased intracranial pressure in two patients, and transient neutropenia. Seven of eight patients with high-risk medulloblastoma and two of two with pineoblastoma remain free of tumor progression following neuraxis irradiation at 8 to 48 months postdiagnosis (median, 18 months). CDDP and VP-16 is a highly active drug combination when given before irradiation in children with high-risk medulloblastoma and other malignant embryonal tumors of the CNS, producing objective responses in at least one site of measurable disease in 10 of 11 newly diagnosed patients, including all of five with gross neuraxis dissemination.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Cisplatino/administración & dosificación , Etopósido/administración & dosificación , Meduloblastoma/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Neoplasias Encefálicas/radioterapia , Niño , Cisplatino/toxicidad , Terapia Combinada , Evaluación de Medicamentos , Etopósido/toxicidad , Femenino , Humanos , Masculino , Meduloblastoma/radioterapia , Meduloblastoma/secundario , Neoplasias de Células Germinales y Embrionarias/radioterapia , Neoplasias de Células Germinales y Embrionarias/secundario , Estudios Prospectivos , Inducción de RemisiónRESUMEN
The clinicopathologic features and response to therapy of 28 patients with non-Ewing's flat bone sarcoma treated at St. Jude Children's Research Hospital, Memphis, Tennessee, over a 25-year period were reviewed. Twenty-two patients had osteosarcoma, four malignant fibrous histiocytoma, one chondrosarcoma, and one fibrosarcoma. Ages at diagnosis ranged from 3 to 24 years (median, 15 years). Primary sites were craniofacial bones in ten patients, pelvis eight, scapula four, ribs two, metatarsal bones two, clavicle one, and vertebra one. All primary tumors were associated with soft tissue extension; none of the patients had metastatic disease at presentation. Six cases represented second malignancies that arose 5 to 16 years after irradiation for an unrelated tumor. Complete excision was possible in ten patients, eight of whom received postoperative chemotherapy. Five of these patients remain free of disease 1.8+ to 13+ years (median, 8.1 years) from diagnosis. Prolonged remissions after adjuvant chemotherapy were achieved in only two of 18 patients after incomplete surgical resection or biopsy. The median survival time in this group was 1 year (range, 0.2-7.7+ years). The remaining 16 patients had progressive local disease, but only two developed concurrent metastases. Thus, complete surgical resection appears to maximize disease-free survival in patients with non-Ewing's flat bone sarcoma. For the large percentage of patients in whom total resection is not possible, because of soft tissue extension and local invasion of bulky tumors, preoperative chemotherapy may increase the likelihood of complete excision and improve long-term survival.
Asunto(s)
Neoplasias Óseas/patología , Sarcoma/patología , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/mortalidad , Neoplasias Óseas/cirugía , Niño , Preescolar , Terapia Combinada , Femenino , Humanos , Masculino , Neoplasias Inducidas por Radiación/tratamiento farmacológico , Neoplasias Inducidas por Radiación/patología , Neoplasias Inducidas por Radiación/cirugía , Sarcoma/tratamiento farmacológico , Sarcoma/mortalidad , Sarcoma/cirugíaRESUMEN
Hyperuricemia is an unusual presenting feature of acute lymphoblastic leukemia (ALL) and is generally associated with a large leukemic cell burden. We describe three children with T-cell ALL who presented with acute renal failure and very high serum uric acid concentrations, despite a relatively small leukemic cell burden. Two of the three patients had normal complete blood counts without circulating blasts or other physical evidence of leukemia. An isolated renal relapse in one case was associated with hyperuricemia, increased renal excretion of uric acid, and renal dysfunction. An unusually high rate of purine catabolism of the lymphoblasts may cause hyperuricemia in these cases. Unexplained hyperuricemia should prompt a search for occult malignancy.