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1.
J Clin Oncol ; 3(6): 776-81, 1985 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-3891922

RESUMO

We assessed the influence of an initial isolated meningeal relapse on treatment outcome in 839 children with acute lymphoblastic leukemia (ALL) who were admitted to St Jude Children's Research Hospital (Memphis) from mid-1967 through mid-1979. The patients were entered in a series of five clinical trials (Total Therapy Studies V through IX), each designed to test one or more modifications of treatment for ALL. Two groups were compared: 699 children who received CNS prophylaxis (2,400-rad craniospinal irradiation or 2,400-rad cranial irradiation plus intrathecal methotrexate) v 56 who did not. Our results, obtained with a time-dependent covariate model and a matching technique, indicate a 2 to 3.5-fold increase in the risk of hematologic relapse or death among patients who experienced an isolated CNS relapse compared with similar patients (matched for leukocyte count and length of complete remission) who remained free of CNS involvement. Of the 107 children with an initial isolated CNS relapse, 89 (83%) have died or have had a subsequent relapse. There was no detectable difference in the rate of hematologic relapse or death after a CNS relapse between patients who had received preventive therapy and those who had not. We conclude that CNS prophylaxis is important both for the prevention of initial CNS leukemia and for reducing the risk of hematologic relapse or death subsequent to a CNS relapse.


Assuntos
Leucemia Linfoide/terapia , Neoplasias do Sistema Nervoso/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doenças da Medula Óssea/patologia , Criança , Ensaios Clínicos como Assunto , Humanos , Leucemia Linfoide/tratamento farmacológico , Leucemia Linfoide/patologia , Metotrexato/uso terapêutico , Neoplasias do Sistema Nervoso/patologia , Neoplasias do Sistema Nervoso/prevenção & controle , Prognóstico , Dosagem Radioterapêutica
2.
J Clin Oncol ; 10(1): 128-33, 1992 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-1727914

RESUMO

PURPOSE: Short stature and obesity have been reported among long-term survivors of childhood acute lymphocytic leukemia (ALL). We examined factors that contribute to these adverse sequelae. PATIENTS AND METHODS: Serial height and weight measurements were analyzed for 91 long-term survivors who were treated for ALL between 1967 and 1975 at a single institution. These patients were all younger than 12 years at diagnosis, were in continuous complete remission, had reached final height, and had height and weight measurements within 1 year of age 18 years. They had received craniospinal (n = 33) or cranial irradiation (n = 58) to total doses of 24 Gy as CNS prophylaxis. Standard deviation scores (SDS) were used to reflect the deviation of height and weight measurements from population means, and the body mass index (BMI; weight divided by height squared) was used in assessing obesity at age 18 years. RESULTS: Short stature (less than fifth percentile) was seen in 41 patients (45%), and obesity (BMI greater than or equal to 24 kg/m2) in 35 (38%). Regression formulae were developed that explain 65% and 62% of the variability in patient height and BMI, respectively. CONCLUSIONS: Risk factors were identified for abnormally short stature, which was defined to be a decrease of 1.5 SDS in height from diagnosis to age 18 years. These factors include younger age and above-average height for age at diagnosis (height SDS greater than 0), craniospinal irradiation, and greater decrease in height SDS during antileukemic therapy. Risk factors for obesity at age 18 years include weight SDS greater than 0 and greater than height SDS at 1 year after the end of chemotherapy.


Assuntos
Estatura , Obesidade/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologia , Adolescente , Índice de Massa Corporal , Neoplasias do Sistema Nervoso Central/prevenção & controle , Criança , Pré-Escolar , Humanos , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco
3.
J Clin Oncol ; 9(3): 400-5, 1991 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1999710

RESUMO

Significant growth retardation was found in 115 survivors of childhood acute lymphoblastic leukemia (ALL) who had completed their growth. These children were diagnosed before 12 years of age and treated on four protocols in a single institution; all received either cranial (n = 78) or craniospinal (n = 37) prophylactic irradiation. Patients' heights at diagnosis were within expected ranges, but final heights were greater than or equal to 1 SD below population means in 74% of cases and greater than or equal to 2 SD in 37%. Effects on growth were more pronounced for children who had received craniospinal irradiation, but decrements were also significant in the cranial irradiation group, with adult heights greater than or equal to 2 SD below population norms in 32%. Growth retardation was significantly greater (P less than .0001) in children who had earlier disease onset. Growth deceleration occurred not only during chemotherapy but during a later period that followed an interval of improved growth in many cases. Thus, late decrements in growth may be missed in studies that do not follow patients until they have attained final heights. These findings indicate that abnormally short stature among survivors of ALL merits further clinical and research attention.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estatura/efeitos dos fármacos , Transtornos do Crescimento/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Estatura/efeitos da radiação , Criança , Terapia Combinada/efeitos adversos , Feminino , Humanos , Estudos Longitudinais , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia
4.
J Clin Oncol ; 3(5): 622-6, 1985 May.
Artigo em Inglês | MEDLINE | ID: mdl-3858436

RESUMO

The frequency and types of major CNS toxicity and morbidity were analyzed in 107 children with acute lymphoblastic leukemia (ALL) following an isolated primary CNS relapse. Seventy-nine (73%) have had multiple subsequent marrow or CNS relapses requiring intensive and prolonged therapy to the CNS. Median survival time is two years. Of these 79 patients, two thirds have had one or more types of major CNS toxicity, including epileptiform seizures (35), moderate to severe structural abnormalities (24 of 27 evaluated), major motor disabilities (9), blindness (2), CNS infection (6), cranial nerve palsies (2), and intracranial lymphoma (2). The remaining 28 patients (26%) have had no or one additional CNS relapse and have received therapy for a median of eight years. One half of this surviving group of patients have had major CNS toxicity, including seizures (9), major motor disability (2), and intracranial calcifications (12/19). When neuropsychologic evaluations were compared between the 28 survivors and 50 of their contemporaries who had been in initial continuous complete remission, the CNS survivors had significantly lower Full Scale IQ scores (83 +/- 16 v 99 +/- 14, P = less than .001) with similarly lower measures of academic performance. The relative contributions of meningeal leukemia itself and intrathecal or radiation therapy to these effects cannot be determined. Since major CNS sequelae occurred in the majority of patients who had a primary isolated CNS relapse, and the frequency of CNS relapse is dependent on the efficacy of the method of CNS prophylaxis, the best method of avoiding major CNS sequelae is the most effective form of CNS prophylaxis.


Assuntos
Doenças do Sistema Nervoso Central/induzido quimicamente , Leucemia Linfoide/tratamento farmacológico , Metotrexato/efeitos adversos , Doença Aguda , Doenças do Sistema Nervoso Central/psicologia , Criança , Terapia Combinada , Humanos , Testes de Inteligência , Leucemia Linfoide/diagnóstico por imagem , Masculino , Neoplasias do Sistema Nervoso/tratamento farmacológico , Neoplasias do Sistema Nervoso/mortalidade , Neoplasias do Sistema Nervoso/prevenção & controle , Radiografia , Recidiva
5.
J Clin Oncol ; 1(12): 793-8, 1983 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-6199470

RESUMO

Cranial computed tomography (CT) was used to estimate the frequency and permanence of brain abnormalities in 108 consecutive children with acute lymphoblastic leukemia (ALL). Fifty-five patients received cranial irradiation (1,800 rad) with intrathecal methotrexate (RT group) and 53 patients received intravenous and intrathecal methotrexate without irradiation (IVIT group). Continuation treatment included sequential drug pairs for the RT group and periodic IVIT methotrexate for the other group. After 12 to 24 months of serial evaluation, five (9%) of the 55 patients in the RT group have had CT scan abnormalities, compared to 10 (19%) of 52 in the IVIT group (p = 0.171). Fourteen of the 15 patients with CT scan abnormalities had focal or diffuse white-matter hypodensity; these have reverted to normal in most cases, reflecting a dynamic process. While such CT findings are of concern and may be an early indicator of central nervous system toxicity, this remains to be proven. Therapy should not be altered on the basis of abnormal CT scans alone but in the context of the entire clinical situation.


Assuntos
Encéfalo/diagnóstico por imagem , Leucemia Linfoide/tratamento farmacológico , Neoplasias Meníngeas/prevenção & controle , Metotrexato/administração & dosagem , Tomografia Computadorizada por Raios X , Adolescente , Encéfalo/efeitos da radiação , Criança , Pré-Escolar , Terapia Combinada , Humanos , Injeções Intravenosas , Injeções Espinhais , Leucemia Linfoide/diagnóstico por imagem , Leucemia Linfoide/radioterapia , Neoplasias Meníngeas/líquido cefalorraquidiano , Neoplasias Meníngeas/diagnóstico por imagem , Proteína Básica da Mielina/líquido cefalorraquidiano
6.
Neurology ; 36(11): 1534-8, 1986 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-3020477

RESUMO

A 10-year-old boy had a right posterior parietal glioblastoma 5 years after completing treatment for acute lymphoblastic leukemia. Interim findings included seizures, leukoencephalopathy, diffuse mineralizing microangiopathy, and abnormal changes in neuropsychological test performance, which, in retrospect, provided information about the location of the tumor. This case highlights unusual sequelae of childhood leukemia and its treatment, as well as the value of neuropsychological procedures in assessing functional status and integrity of the brain.


Assuntos
Neoplasias Encefálicas/psicologia , Glioblastoma/psicologia , Leucemia Linfoide/psicologia , Testes Neuropsicológicos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/etiologia , Criança , Glioblastoma/diagnóstico por imagem , Glioblastoma/etiologia , Humanos , Leucemia Linfoide/complicações , Leucemia Linfoide/terapia , Masculino , Tomografia Computadorizada por Raios X
7.
Am J Med ; 77(2): 355-8, 1984 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-6380290

RESUMO

Two patients with advanced lymphoma involving the lungs that was resistant to chemotherapy had an initial excellent response to interferon therapy. After two months of stable disease, alpha interferon A therapy was discontinued, with relapse of a few months later. Both patients had extensive pulmonary involvement with relapse of the lymphoma, and both showed a dramatic response to retreatment with alpha interferon A. Unusual interferon-related pulmonary complications were observed in one patient, and their management is detailed.


Assuntos
Interferon Tipo I/uso terapêutico , Neoplasias Pulmonares/terapia , Linfoma/terapia , Recidiva Local de Neoplasia/terapia , Corticosteroides/uso terapêutico , Adulto , Ensaios Clínicos como Assunto , DNA Recombinante , Humanos , Interferon Tipo I/efeitos adversos , Interferon Tipo I/genética , Neoplasias Pulmonares/diagnóstico por imagem , Metástase Linfática , Linfoma/diagnóstico por imagem , Masculino , Radiografia , Síndrome do Desconforto Respiratório/etiologia
8.
Int J Radiat Oncol Biol Phys ; 36(5): 1251-61, 1996 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-8985051

RESUMO

PURPOSE: Delayed cerebral necrosis (DN) is a significant risk for brain tumor patients treated with high-dose irradiation. Although differentiating DN from tumor progression is an important clinical question, the distinction cannot be made reliably by conventional imaging techniques. We undertook a pilot study to assess the ability of proton magnetic resonance spectroscopy (1H MRS) to differentiate prospectively between DN or recurrent/residual tumor in a series of children treated for primary brain tumors with high-dose irradiation. METHODS AND MATERIALS: Twelve children (ages 3-16 years), who had clinical and MR imaging (MRI) changes that suggested a diagnosis of either DN or progressive/recurrent brain tumor, underwent localized 1H MRS prior to planned biopsy, resection, or other confirmatory histological procedure. Prospective 1H MRS interpretations were based on comparison of spectral peak patterns and quantitative peak area values from normalized spectra: a marked depression of the intracellular metabolite peaks from choline, creatine, and N-acetyl compounds was hypothesized to indicate DN, and median-to-high choline with easily visible creatine metabolite peaks was labeled progressive/recurrent tumor. Subsequent histological studies identified the brain lesion as DN or recurrent/residual tumor. RESULTS: The patient series included five cases of DN and seven recurrent/residual tumor cases, based on histology. The MRS criteria prospectively identified five out of seven patients with active tumor, and four out of five patients with histologically proven DN correctly. Discriminant analysis suggested that the primary diagnostic information for differentiating DN from tumor lay in the normalized MRS peak areas for choline and creatine compounds. CONCLUSIONS: Magnetic resonance spectroscopy shows promising sensitivity and selectivity for differentiating DN from recurrent/progressive brain tumor. A novel diagnostic index based on peak areas for choline and creatine compounds may provide a simple discriminant for differentiating DN from recurrent or residual primary brain tumors.


Assuntos
Neoplasias Encefálicas/diagnóstico , Encéfalo/patologia , Recidiva Local de Neoplasia/diagnóstico , Radioterapia/efeitos adversos , Adolescente , Neoplasias Encefálicas/radioterapia , Criança , Pré-Escolar , Feminino , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Necrose , Neoplasia Residual , Sensibilidade e Especificidade
9.
Hybridoma ; 3(3): 233-45, 1984.
Artigo em Inglês | MEDLINE | ID: mdl-6500584

RESUMO

Monoclonal antibodies to tumor-associated antigens (TAA) of human colorectal cancer were elicited using immunosorbents of lectins combined with peripheral protein extracts of xenografted colon adenocarcinoma. This method of immunization was compared with whole cells from surgical specimens and to crude membranes from xenografted tumors. The immunosorbent immunogens were superior to the other immunogens in three ways: (1) the number of hybrids reactive with colon tumor cells or extracts, but not with lymphoid cells or extracts, (2) the number of stable hybrids after cloning, and (3) the number of hybridoma clones reactive with tissue sections of colon tumors, but not normal colonic mucosa. In addition, lectin immunosorbents elicited primarily IgG antibodies, especially IgG3, with almost 50% of the clones of interest reacting to seemingly less immunogenic glycoproteins. The improved elicitation of monoclonal antibodies to TAA by the use of lectin immunosorbents and peripheral protein extracts has considerable potential for generating reagents useful in diagnosis and therapy of human tumors.


Assuntos
Anticorpos Monoclonais/classificação , Antígenos de Neoplasias/imunologia , Neoplasias do Colo/imunologia , Neoplasias Retais/imunologia , Animais , Anticorpos Monoclonais/biossíntese , Anticorpos Antineoplásicos/imunologia , Especificidade de Anticorpos , Humanos , Imunização , Imunoglobulina G/classificação , Camundongos
10.
Am J Pediatr Hematol Oncol ; 11(1): 93-105, 1989.
Artigo em Inglês | MEDLINE | ID: mdl-2653080

RESUMO

Therapy for occult or overt meningeal leukemia produces subclinical or clinical neurotoxicity in a variable proportion of children with acute lymphoblastic leukemia (ALL). The type, frequency, and permanence of these central nervous system (CNS) changes depend primarily on the therapy itself, although the contribution of additional factors, such as young age, may be substantial. Neurotoxicity in patients who have received 2,400 cGy cranial irradiation plus 5 concurrent doses of intrathecal methotrexate as CNS prophylaxis has been characterized more fully than the CNS changes accompanying other forms of therapy. Cross-sectional studies using cranial computed tomography scans to evaluate structural changes in the brain have shown ventricular dilatation in 15%, white matter hypodensity in 3.5%, and calcifications in 8%. The principal neuroendocrine effect is decreased growth velocity during therapy and adolescence, with significant decreases in final height in approximately one-third of children. Secondary cerebral gliomas with a poor prognosis are being reported with increasing regularity, but the true risk of this complication is still unknown. Use of parenteral methotrexate as the sole method of CNS prophylaxis is associated with transient focal white matter hypodensity. Neuroendocrine and neuropsychologic sequelae associated with this therapy are minimal; however, much of the available information is based on patients treated with regimens that had unacceptably high CNS relapse rates or whose length of follow-up was brief. With more aggressive, and hence more effective, prophylaxis with intrathecal methotrexate, spinal cord myelopathy may become a significant new area of neurotoxicity. Clinically significant CNS toxicity develops in the majority of patients who receive treatment for meningeal relapse. The leukemia itself is a prime contributing factor to this neurotoxicity. In patients who are subsequently cured of leukemia, acute neurotoxicity consists mainly of seizures; the most significant sequelae appearing after the cessation of therapy consists of significant drops in full scale IQ.


Assuntos
Sistema Nervoso Central/efeitos dos fármacos , Citarabina/efeitos adversos , Metotrexato/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Sistema Nervoso Central/efeitos da radiação , Criança , Citarabina/uso terapêutico , Humanos , Neoplasias Meníngeas/tratamento farmacológico , Neoplasias Meníngeas/radioterapia , Metotrexato/uso terapêutico , Sistemas Neurossecretores/anormalidades , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia
11.
Cancer ; 45(9): 2274-8, 1980 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-6929724

RESUMO

Central nervous system (CNS) "prophylaxis" is critical in the treatment of acute lymphocytic leukemia (ALL). The standard method employed combines cranial radiation (CRT) and intrathecal methotrexate (IT MTX). Recently, a 52% incidence of abnormal computed tomography (CT) brain scans was found in asymptomatic children with ALL whose CNS prophylaxis consisted of CRT and either IT MTX or intrathecal cytosine arabinoside (IT Ara-C). In the present study, CT brain scans were studied in 43 asymptomatic children with ALL in continuous complete remission. The CNS prophylaxis consisted of IT MTX alone in 10 patients and IT MTX combined with intermediate-dose intravenous MTX in 33 patients. No patient had received CRT. The patients' ages at the time of diagnosis ranged from 22 months to 17 years, 7 months. The time interval from completion of CNS prophylaxis to CT scanning ranged from ten to 59 months. Only one CT scan was clearly abnormal; it showed mildly dilated ventricles and visualization of the cortical sulci. The CT scans of 7 additional patients were classified as abnormal because of borderline dilatation of the lateral ventricles (3 patients) and/or visualization of the cortical sulci (7 patients). No patient demonstrated areas of decreased cerebral attenuation coefficient or intracerebral calcification--findings previously ascribed to the use of methotrexate. Clinical leukoencephalopathy has not been observed in any of our patients. This would suggest that MTX alone in the absence of CNS leukemia or CRT is highly unlikely to produce structural CNS abnormalities detectable by CT.


Assuntos
Encéfalo/diagnóstico por imagem , Leucemia Linfoide/tratamento farmacológico , Metotrexato/efeitos adversos , Adolescente , Encefalopatias/diagnóstico , Doenças do Sistema Nervoso Central/prevenção & controle , Criança , Pré-Escolar , Humanos , Lactente , Injeções Intravenosas , Injeções Espinhais , Remissão Espontânea , Fatores de Tempo , Tomografia Computadorizada por Raios X
12.
Cancer Treat Rep ; 62(2): 239-45, 1978 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-346212

RESUMO

Eight patients with advanced metastatic osteogenic sarcoma were treated with cis-dichlorodiammineplatinum(II) (DDP). Prior to DDP, seven patients had amputations and all had received adjuvant adriamycin (ADR) therapy. In addition, prior to DDP, six patients had received high-dose methotrexate. There was one complete response (pulmonary metastases) and four partial responses (three metastases in the lungs and one in the bone). One additional patient, with local recurrence of osteogenic sarcoma of the mandible following initial resection and adjuvant ADR, was retreated with surgery and DDP and is disease-free for greater than 3 years. The cumulative dose ranged from 300 to 660 mg/m2. Toxicity included irreversible kidney damage in two patients, transient severe hematologic suppression in two patients, and nausea and vomiting in all patients. DDP is a new effective agent in the treatment of osteogenic sarcoma.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Cisplatino/uso terapêutico , Osteossarcoma/tratamento farmacológico , Adolescente , Adulto , Cisplatino/efeitos adversos , Ensaios Clínicos como Assunto , Feminino , Humanos , Masculino , Metástase Neoplásica , Remissão Espontânea
13.
Cancer Treat Rep ; 67(12): 1123-6, 1983 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-6197165

RESUMO

Thirty-two patients with small cell carcinoma of the lung were given chest radiotherapy to progressive intrathoracic tumor after failing chemotherapy. Two-thirds of these patients received split-course treatment at a dose of 4000 rad in 10 fractions. Sixteen of 25 evaluable patients (64%) had an objective response, but only five responders did not progress within the port during life. Median time to local progression was 16 weeks. Two patients, one of whom was given concurrent chemotherapy, survived greater than 18 months, and one is free of disease at 31+ months. Short-term palliation of chest disease and occasional long-term survival are possible with this regimen, although most patients will die with systemic disease within several months. Small cell carcinoma of the lung is less responsive to irradiation as second-line therapy than as initial therapy, but doses of greater than or equal to 4000 rad can offer symptomatic relief in many cases and, rarely, survival beyond 18 months.


Assuntos
Carcinoma de Células Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Probabilidade , Dosagem Radioterapêutica , Fatores de Tempo
14.
Lancet ; 2(8417-8418): 1422-4, 1984 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-6151043

RESUMO

Features of seizures in children with acute lymphoblastic leukaemia were examined in relation to the type of treatment received for central nervous system prophylaxis. Of the 1289 patients in the study, 132 (10%) had experienced one or more seizures. In 96 the seizures had not been associated with any recognisable aetiology and, with 3 exceptions, had been generalised or focal motor in type. Status epilepticus had occurred in one-third of the group with seizures. Initial seizure rates among patients in continuous complete remission were significantly related to the method of central nervous system prophylaxis. Those who had received intrathecal methotrexate repeatedly with or without moderate doses of methotrexate intravenously or prior prophylactic cranial irradiation had a 20-fold higher seizure risk during remission induction, and a 37-fold higher risk during the 6th to 12th month of therapy, than did those who had received irradiation and only five intrathecal injections of methotrexate early in the course of treatment. Other clinical factors associated with an increased frequency of seizures were escalation of intravenous methotrexate dosage following cranial irradiation and treatment of meningeal leukaemia with intrathecal methotrexate. Parenterally administered methotrexate thus seems to increase susceptibility to seizure development in childhood leukaemia patients.


Assuntos
Epilepsia/complicações , Leucemia Linfoide/complicações , Neoplasias Meníngeas/complicações , Sistema Nervoso Central/diagnóstico por imagem , Sistema Nervoso Central/efeitos da radiação , Criança , Seguimentos , Humanos , Leucemia Linfoide/diagnóstico por imagem , Leucemia Linfoide/tratamento farmacológico , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/prevenção & controle , Metotrexato/administração & dosagem , Radiografia , Estudos Retrospectivos
15.
Pediatr Neurosurg ; 22(6): 289-97; discussion 98, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-7577662

RESUMO

Malignant pediatric tumors of the central nervous system (CNS) have a poor prognosis, with local failure rates as high as 50%. In an attempt to improve local tumor control, we used stereotactic interstitial therapy with 125I implants in patients with recurrent/secondary or newly diagnosed CNS malignancies. Catheters were placed using computed tomography (CT) guidance; computerized dosimetry was completed with the aid of orthogonal films. Implants delivered 1,000 cGy/day to the tumor periphery (0.5 cm beyond the boundary of enhancement on CT scans), to a total dose of 60 Gy. Hyperfractionated external beam irradiation (HEBI), started 2-4 weeks after removal of implants, delivered total doses of 66-70.4 Gy in 110-cGy fractions twice daily to a 3-cm margin around the implant volume. Eight of the 11 patients with newly diagnosed tumors also received 48.4 Gy HEBI to the craniospinal axis. Tumor regression was noted at 2 months after implantation in the 4 patients treated for recurrent/secondary tumors; local progression was subsequently documented in 2 cases at 6 and 20 months after implantation, while a third patient died 6 months after implantation with no evidence of local recurrence. The remaining recurrent/secondary tumor patient has no evidence of active recurrence 15 months after implantation. Local control was maintained in 9 of the 11 patients treated for primary tumors for a median of 27 months (range 15 to 48+ months). The two local failures occurred at 5 and 7 months after implantation. Six patients are alive without evidence of progressive disease (median = 23 months after implantation). There were no severe acute toxicities, but 7 patients later developed histologically confirmed tumor necrosis. Quality of life assessment (QLA) following initial primary therapy with implantation was evaluated utilizing an established criteria and found to be excellent with only one child showing marked QLA score decrease which was related to neurosurgical intervention for radiation-induced necrosis and dysfunctional family social situation. This small series suggests that stereotactic 125I implantation followed by HEBI merits further evaluation in selected children with supratentorial malignant lesions.


Assuntos
Braquiterapia/métodos , Irradiação Craniana/métodos , Radioisótopos do Iodo/uso terapêutico , Neoplasias Supratentoriais/radioterapia , Adolescente , Encéfalo/efeitos da radiação , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/radioterapia , Lesões por Radiação/mortalidade , Dosagem Radioterapêutica , Técnicas Estereotáxicas , Neoplasias Supratentoriais/mortalidade , Taxa de Sobrevida
16.
Ann Intern Med ; 98(5 Pt 1): 598-602, 1983 May.
Artigo em Inglês | MEDLINE | ID: mdl-6342490

RESUMO

Nineteen patients with advanced refractory metastatic breast cancer no longer responsive to chemotherapy were treated in the first phase II efficacy trial of recombinant leukocyte A interferon (IFL-rA), a highly purified single molecular species of alpha interferon prepared by recombinant DNA methods. Patients received a previously determined maximum tolerated dose for this agent (50 X 10(6) U/m2 body surface area) by intramuscular injection three times weekly for up to 3 months. The symptoms of toxicity observed in this trial resemble those previously reported for alpha interferons and include fever, chills, fatigue, anorexia, and leukopenia. All patients required dose reductions, most often for reasons of severe fatigue. Of the 17 patients evaluable for tumor response, one patient had stable disease and 16 had evidence of tumor progression. We conclude that IFL-rA is not an active agent in the treatment of advanced, refractory breast cancer when used at a maximum tolerated dose on this treatment schedule.


Assuntos
Neoplasias da Mama/terapia , Interferon Tipo I/uso terapêutico , Leucócitos/imunologia , Adulto , Idoso , Neoplasias da Mama/patologia , Ensaios Clínicos como Assunto , Fadiga/etiologia , Feminino , Gastroenteropatias/etiologia , Humanos , Injeções Intramusculares , Interferon Tipo I/efeitos adversos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Trombocitopenia/etiologia
17.
Cancer Immunol Immunother ; 15(2): 144-8, 1983.
Artigo em Inglês | MEDLINE | ID: mdl-6307500

RESUMO

Highly purified human lymphoblastoid interferon (HLBI) derived from virus-stimulated Namalwa cells was administered by 6-h IV infusion or IM injection to 40 patients with a variety of disseminated malignancies refractory to standard therapy. Each patient received doses escalating from 0.1 to 50 X 10(6) U for up to 5 weeks. Extensive monitoring for clinical effect, toxicity, and pharmacokinetics has revealed higher peak serum interferon levels and somewhat more pronounced systemic toxicity for the IV than for the IM route of administration. Objective evidence of tumor regression was observed in two patients receiving HLBI IV.


Assuntos
Interferon Tipo I/uso terapêutico , Neoplasias/terapia , Linfócitos B , Linfoma de Burkitt , Linhagem Celular , Ensaios Clínicos como Assunto , Esquema de Medicação , Seguimentos , Humanos , Infusões Parenterais , Injeções Intramusculares , Interferon Tipo I/administração & dosagem , Interferon Tipo I/toxicidade , Vírus da Parainfluenza 1 Humana
18.
JAMA ; 248(19): 2461-6, 1982 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-6752447

RESUMO

Eighty-one patients with a variety of refractory disseminated malignant neoplasms have been treated in the first multiple fixed-dose phase I trial of recombinant leukocyte A interferon (IFL-rA). Each patient received IFL-rA by intramuscular injection, three times weekly for 28 days. Dosages were escalated in different patients from 1 to 136 x 10(6) units per injection. The toxic reactions seen with IFL-rA resembled those of nonrecombinant leukocyte interferon and included fever, chills, fatigue, anorexia, myalgia, headache, occasional nausea and vomiting, and dose-dependent reversible leukopenia and hepatic transaminase elevations. The pharmacokinetics of IFL-rA were also comparable with nonrecombinant leukocyte interferon. Objective evidence of antitumor activity was seen in non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Hodgkin's disease, breast cancer, and melanoma, indicating that IFL-rA, the first genetically engineered biological response modifier available for testing in cancer patients, is biologically active in vivo.


Assuntos
Interferon Tipo I/administração & dosagem , Neoplasias/terapia , Anorexia/etiologia , Ensaios Clínicos como Assunto , DNA Recombinante , Relação Dose-Resposta a Droga , Avaliação de Medicamentos , Fadiga/etiologia , Febre/etiologia , Humanos , Injeções Intramusculares , Interferon Tipo I/efeitos adversos , Interferon Tipo I/sangue , Cinética , Leucopenia/etiologia , Trombocitopenia/etiologia
19.
J Biol Response Mod ; 3(6): 599-607, 1984 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-6439828

RESUMO

Thirty-three patients were treated in an escalating single-dose trial of partially purified nonrecombinant interferon-gamma (IFN-gamma). The first seven patients received intramuscular injections of IFN-gamma in doses up to 20 X 10(6) units/m2. When it became clear that these patients had no detectable antiviral activity in their serum, subsequent patients were treated by the intravenous route of administration, generally with 2-h infusions. A total of 26 patients received the agent intravenously in single escalating doses ranging from 0.2 to 60 X 10(6) units/m2, on a twice-weekly schedule for 4-6 weeks. The most common toxicities encountered included fever, chills, fatigue, anorexia, and occasional nausea and vomiting. No myelosuppression or hepatic toxicity was observed. A maximum tolerated dose for single-dose intravenous administration was defined as 50 X 10(6) units/m2 on the basis of unacceptable fatigue and prolonged systolic hypotension. Antiviral activity was detected in the serum following doses greater than 2 X 10(6) units/m2 when the IFN-gamma was administered intravenously. No evidence of antitumor activity was seen in this Phase I trial, although the treatment regimen employed did not lead to high or prolonged levels of serum IFN activity in the majority of patients. An accurate assessment of the antitumor activity of this particular IFN-gamma preparation will require Phase II trials employing multiple-treatment regimens.


Assuntos
Interferon gama/uso terapêutico , Neoplasias/terapia , Avaliação de Medicamentos , Humanos , Injeções Intramusculares , Injeções Intravenosas , Interferon gama/administração & dosagem , Interferon gama/efeitos adversos , Interferon gama/sangue
20.
J Immunol ; 132(4): 1611-3, 1984 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-6699400

RESUMO

Human-murine hybridomas, generated by fusion of human CLL cells with non-Ig-secreting murine myeloma NS-1, and secreting the IgM kappa expressed on the CLL cell surface, were grown in the peritoneal cavity of doubly pristane-primed nude mice to produce large quantities of highly concentrated human IgM kappa for the development of anti-idiotype monoclonal antibodies. Although the hybridomas secreted only 0.8 to 1.5 micrograms/ml/10(6) cells in tissue culture, they produced 8 to 12 ml of ascites from two mice containing 1.7 mg/ml of human IgM. Partial purification was then easily accomplished by euglobulin precipitation. Two weekly injections of 100 micrograms of this material into BALB/c mice resulted in the development of both anti-idiotypic and anti-human IgM antibodies. This system overcomes the major hurdle of generating sufficient quantities of the human idiotypic Ig to immunize and screen for specific murine antiidiotypes, and provides the material to produce these therapeutically promising reagents rapidly for clinical trials. This is, to our knowledge, the first report of a human Ig produced in mouse ascites.


Assuntos
Anticorpos Monoclonais/biossíntese , Líquido Ascítico/imunologia , Idiótipos de Imunoglobulinas/biossíntese , Imunoglobulina M/biossíntese , Animais , Anticorpos Monoclonais/administração & dosagem , Humanos , Hibridomas/imunologia , Idiótipos de Imunoglobulinas/imunologia , Idiótipos de Imunoglobulinas/isolamento & purificação , Imunoglobulina M/isolamento & purificação , Leucemia Linfoide/imunologia , Leucemia Linfoide/terapia , Masculino , Camundongos , Camundongos Nus
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