摘要:

AbstractIn neuroblastoma, N‐myc amplification and loss of heterozygosity for the short arm of chromosome 1 (LOH 1p) are common genetic abnormalities. We have recently shown that the presence of additional material of the long arm of chromosome 17 (add.17q) also occurs relatively frequently. In the present study, we analyzed a series of 55 tumors for LOH 1p, N‐myc amplification and add.17q, using Southern blot analysis with polymorphic DNA probes of pairs of tumor and constitutional DNA. We determined the correlation of these parameters with clinical variables, such as age, stage, serum lactate dehydrogenase (LDH) and ferritin and also with outcome. LOH 1p occurred in 20 out of 55 cases (36%) and was found more often in stage III/IV tumors and in the older age group, although both correlations were not statistically significant. N‐myc amplification was only demonstrated in 12 tumors with concomitant LOH 1p and was not present in the 35 cases without LOH 1p. Add.17q was found in 20/53 (38%) informative cases. LOH 1p was shown to be the most significant predictor of a poor outcome (P<0.00001), independent of age and stage. LOH 1p is also of prognostic value in those cases without N‐myc amplification, indicating a stronger prognostic value for LOH 1p. Add.17q was also associated with an unfavourable prognosis, although this was less significantly then with LOH 1p (P= 0.00004). © 1995 Wi1ey

ISSN:0098-1532    

DOI:10.1002/mpo.2950240402

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractThe survival from acute lymphoblastic leukaemia in childhood is now approximately 60–70%, and from acute myeloid leukaemia, up to 50%. However, there is little information on the effects of intensive chemotherapy and radiotherapy used in the treatment of these conditions on lung function and exercise capacity in the long term.Seventy survivors of acute leukaemia from one centre in the UK were studied. Measurements of lung volumes, spirometry and transfer factor were made. Each child also performed a standard, symptom‐limited maximal exercise test on a cycle ergometer. Predictive equations for indices of lung function and exercise tolerance were calculated from 146 age‐ and sex‐matched control subjects. The results of the survivors of leukaemia were compared to these.There was a significant reduction of forced expiratory volume in one second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), and transfer for carbon monoxide (DLCO;P<0.05 for each measurement), in the survivors of leukaemia when compared to the control subjects. In addition, there was a mild but significant reduction of both maximal and submaximal indices of exercise capacity in the leukaemic group. A multivariate analysis was carried out to identify those variables acting independently to reduce lung volumes. For FEV1, FVC and TLC, these were craniospinal irradiation, cyclophosphamide and chest complications during treatment. For a reduction in DLCO, the significant factors were administration of anthracyclines, craniospinal irradiation and bone marrow transplantation.Survivors of acute leukemia have impaired pulmonary function and exercise capacity. Long‐term cardiopulmonary follow‐up may be necessary and new regimens devised which reduce long‐term toxicity without compromising survival rates. © 1995

ISSN:0098-1532    

DOI:10.1002/mpo.2950240403

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractThe role of screening for early detection of Wilms' tumour (WT) in patients with aniridia (A), Beckwith‐Weidemann syndrome (BWS) and hemihypertrophy (HH) has been explored. Of the 1,622 Wilms' tumour patients registered with the National Childhood Cancer Registry from 1971 to 1991, 41 were recorded as having A, BWS or HH. Twenty‐eight of these had their anomaly diagnosed before the WT and 13 had screening procedures carried out, mainly abdominal ultrasound. In 8 patients the screening procedure detected the WT. There was no significant difference in stage distribution or outcome for any of the three subgroups who were not screened, screen‐positive or screen‐negative. We conclude that regular screening with abdominal ultrasound is not of proven value. Parents should be taught abdominal palpation and advised to seek appropriate advice for untoward symptoms. © 1995 Wi1ey

ISSN:0098-1532    

DOI:10.1002/mpo.2950240404

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractVincristine (VCR) has been widely used to treat childhood malignancies for over thirty years, but its plasma disposition has not yet been well‐defined. Therefore, we conducted a pharmacokinetic study of VCR in 17 children with acute lymphoblastic leukemia (ALL) receiving the first dose of VCR. A new high‐performance liquid chromatographic assay was used for the measurement of VCR in plasma. A two‐compartment pharmacokinetic model was fit to the data by nonlinear least‐squares regression. Estimated pharmacokinetic parameters were highly variable; mean (S.D.) volume of distribution at steady‐state was 360 (176) L.m−2; total body clearance was 431 (238) ml. min−1.m−2, and elimination half‐life was 823 (390) min. These results were compared to data from eight adults with lung cancer. Mean volume of distribution in adults and children were similar, but VCR clearance was significantly larger in children (P= 0.01), resulting in a significantly longer elimination half‐life in the adults (P<0.01).We conclude that administration of a standard dosage of VCR to children with ALL results in a highly variable systemic drug exposure, which may have implications for the oncolytic effect and/or toxicity in individual patients. Comparison of data from children and adults suggests that VCR elimination rate is a function of age; this could account for more severe neurotoxicity in older patients. However, it cannot be excluded that differences between the children and adults may be due to other variables than age. Future studies should focus on the possible influence of multidrug resistance modulating agents on VCR pharmacokinetics and on pharmacokinetic‐pharmacodynamic relationships in individual patients.

ISSN:0098-1532    

DOI:10.1002/mpo.2950240405

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractWe conducted a dose escalation trial of cyclophosphamide plus Sargramostim in the therapy of patients with newly diagnosed or recurrent central nervous system tumors. Cyclophosphamide was administered at doses ranging between 1.0 and 2.5 g/m2daily for two doses. Sargramostim was administered at a fixed dose of 250 μg/m2subcutaneously twice a day beginning 24 hours after the second cyclophosphamide dose and continuing through the leukocyte nadir until the absolute neutrophil count (ANC) was>1,000 cells/μl for two consecutive days. The MTD for patients who had not received any prior chemotherapy and who had received either no radiotherapy or radiotherapy confined to the cranium was 2.0 g/m2daily for two doses. The MTD for patients previously treated with chemotherapy or neuraxis radiotherapy was also 2.0 g/m2daily for two doses. Responses were seen in patients with medulloblastoma (8/9), glioblastoma multiforme (2/13), germinoma (1/1), and pineoblastoma (1/2). © 1995 Wi1ey‐Liss

ISSN:0098-1532    

DOI:10.1002/mpo.2950240406

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractDiabetes insipidus (DI) in Langerhans cell histiocytosis (LCH) is a common complication of unclear etiology. The incidence varies among different publications from 15% to 50%. In the prospective DAL‐HX 83 study, 19 out of 199 patients (9.5%) registered with newly diagnosed LCH were diagnosed to have DI. All patients were stratified according to uniform criteria. One hundred and six patients with disseminated disease were treated with standardized polychemotherapy promptly after diagnosis. At the time of diagnosis of LCH, DI was already established in 8 out of 199 patients (4%). After diagnosis, DI occurred in only one out of the remaining 91 patients with localized disease (1%) and in 10 out of 100 remaining patients with disseminated disease (10%). In 8 patients, the onset of DI was associated with other signs of active LCH. The cumulative risk to develop DI after a median observation time of 5 years 3 months was 11%. Retrospective analysis of clinical features revealed multisystem involvement, skull and orbital lesions, and in particular intracranial extension from osseous lesions to constitute risk factors for DI. Magnetic resonance imaging studies (MRI) were available in 12 patients and showed abnormalities of the pituitary region in 10 children. In none of the patients with established DI was it reversed or ameliorated by any treatment. However, the rapid institution of systemic chemotherapy for disseminated disease seems to prevent the occurrence of DI and may be responsible for the low frequency of DI in the DAL‐HX 83 study. © 1995 Wi1ey‐Li

ISSN:0098-1532    

DOI:10.1002/mpo.2950240407

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

ISSN:0098-1532    

DOI:10.1002/mpo.2950240408

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractLevamisole is an immunomodulatory agent which is used in the adjuvant therapy of certain malignancies. Agranulocytosis is the most commonly reported hematologic side effect associated with this drug. We report here a patient who developed thrombocytopenia nearly 2 years after starting adjuvant levamisole therapy for malignant melanoma. In this case, thrombocytopenia was shown to be levamisole‐related by re‐challenge with the drug. Levamisole‐induced thrombocytopenia (LIT) has been rarely diagnosed, but may be seen more frequently as increasing numbers of patients receive adjuvant therapy for colon cancer and melanoma. © 1995 Wi1ey‐

ISSN:0098-1532    

DOI:10.1002/mpo.2950240409

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractA child was diagnosed in 1969 as having acute lymphoblastic leukaemia (ALL) and received chemotherapy. On bone marrow relapse in 1973, he was treated with cranial irradiation (20 Gy) in addition to chemotherapy. He continues in complete remission 19 years after his relapse. At age 25 years, he presented with headaches and left hemiparesis. Computerised tomograph demonstrated a large, enhancing right‐sided intracranial tumour. Angiography was performed and showed the right internal carotid artery was occluded. Most of the right hemisphere was supplied from the external carotid via the middle meningeal artery. The left posterior cerebral artery and the left anterior cerebral artery were absent presumably as a result of radiation‐induced arteritis. A resection of an anaplastic meningioma arising from the right sphenoidal ridge was achieved. There was a rapid improvement in function and he returned to work. Vasculopathy of the large intracranial arteries has been described after high dose radiation. It may occur as in this case after moderate dose radiation. There is a correlation with meningioma. There is a possibility that large artery vasculopathy will be present in a proportion of patients irradiated for ALL. The long lag time between irradiation and the development of meningioma may mean that, as survivors of childhood ALL enter their third decade since cure, this tumour may be seen increasingly. © 1995 Wi1ey‐Li

ISSN:0098-1532    

DOI:10.1002/mpo.2950240410

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractTransitional cell carcinoma of the bladder rarely occurs in young female patients. We present a case of bladder carcinoma which appeared after treatment with cyclophosphamide, in a 14‐year‐old girl genetically predisposed to bladder cancer. © 1995 Wi1ey‐Li

ISSN:0098-1532    

DOI:10.1002/mpo.2950240411

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY