139 results on '"Jon Pritchard"'
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2. Immediate nephrectomy versus preoperative chemotherapy in the management of non-metastatic Wilms’ tumour: Results of a randomised trial (UKW3) by the UK Children’s Cancer Study Group
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J. Imeson, Jenny Walker, Peter Gornall, Roger E. Taylor, Boo Messahel, Pat Sartori, Rosemary S. Shannon, Anna Kelsey, Jon Pritchard, Carolyn Hutton, Suzanne Stevens, Kathy Pritchard-Jones, Helen Middleton, Chris Mitchell, Juliet Hale, David Machin, Gordan M. Vujanic, Gill Levitt, and Richard Grundy
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Male ,Cancer Research ,Vincristine ,medicine.medical_specialty ,Time Factors ,Adolescent ,medicine.medical_treatment ,Nephrectomy ,Wilms Tumor ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Stage (cooking) ,Child ,Neoplasm Staging ,Chemotherapy ,business.industry ,Infant ,Cancer ,Wilms' tumor ,medicine.disease ,Combined Modality Therapy ,Survival Analysis ,Kidney Neoplasms ,Surgery ,Radiation therapy ,Treatment Outcome ,Oncology ,Chemotherapy, Adjuvant ,Child, Preschool ,Dactinomycin ,Female ,business ,medicine.drug ,Kidney disease - Abstract
Immediate nephrectomy versus preoperative chemotherapy in the management of non-metastatic Wilms' tumour: Results of a randomised trial (UKW3) by the UK Children's Cancer Study Group Purpose: To determine if patients receiving preoperative chemotherapy with vincristine and actinomycin D for non-metastatic Wilms' tumour have a more advantageous stage distribution and so need less treatment compared to patients who have immediate nephrectomy, without adversely affecting outcome. Methods: Between 1991 and 2001, a total of 205 patients with newly diagnosed non-metastatic renal tumours, of which 186 had Wilms' histologies, were randomly assigned either to immediate surgery or to 6 weeks preoperative chemotherapy and then delayed surgery. Both groups of children received postoperative chemotherapy according to tumour stage and histology determined at the time of nephrectomy Results: There was a significant improvement in the stage distribution for patients with Wilms' histologies receiving delayed surgery compared to those having immediate nephrectomy (stage L 65.2% versus 54.3%; stage 11: 23.9% versus 14.9%; stage 111: 9.8% versus 29.8%, chi(2) test for trend = 7.02, p = 0.008). This improvement resulted in 20% fewer children receiving radiotherapy or doxorubicin yet event-free and overall survivals at 5 years of 79.6% and 89.0%, respectively, were similar in the two groups. Conclusion: Six weeks of preoperative chemotherapy with vincristine and actinomycin D results in a significant shift towards a more advantageous stage distribution and hence reduction in therapy, while maintaining excellent event free and overall survival in children with non-metastatic Wilms' tumour. Around 20% of survivors were therefore spared the late-effects of doxorubicin or radiotherapy. Our results suggest that all children with non-metastatic Wilms' tumour should receive chemotherapy prior to tumour resection. (c) 2006 Elsevier Ltd. All rights reserved.
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- 2006
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3. SUCCESSFUL TREATMENT OF MULTIFOCAL UNRESECTABLE HEPATOBLASTOMA WITH CHEMOTHERAPY ONLY
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Jon Pritchard, Asim Qidwai, Asim Noor Rana, and M. Shamvil Ashraf
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Hepatoblastoma ,medicine.medical_specialty ,medicine.medical_treatment ,Liver transplantation ,Disease-Free Survival ,Nephrotoxicity ,Ototoxicity ,Antineoplastic Combined Chemotherapy Protocols ,Biopsy ,medicine ,Humans ,Cardiotoxicity ,Chemotherapy ,medicine.diagnostic_test ,business.industry ,Remission Induction ,Hematology ,medicine.disease ,Surgery ,medicine.anatomical_structure ,Oncology ,Vincristine ,Pediatrics, Perinatology and Child Health ,Dactinomycin ,Female ,Tomography, X-Ray Computed ,business ,Left lobe of liver - Abstract
We report the case of a girl with multi-focal hepatoblastoma in whom chemotherapy alone has resulted in long term event-free survival and possibly cure, without any surgical procedure apart from biopsy for initial diagnosis. At presentation she had a large tumour arising from the left lobe of liver and two other separate masses were noted in the right lobe, but the lungs were free of metastases. Histology showed a foetal type of hepatoblastoma. The serum alpha-feto protein (AFP) level was 44,000 iu/litre. Chemotherapy was started using the triple drug regime recommended for "high risk" (of relapse) patients in the SIOPEL 2 hepatoblastoma protocol of the International Society of Paedaitric Oncology (SIOP). Within a few weeks her abdominal girth decreased, the child became much more comfortable. Drug-induced cardiotoxicity, ototoxicity and nephrotoxicity were not observed. After a total of 4 courses of chemotherapy (completed at the end of August 1998) a CT scan showed that all 3 tumours were smaller but that there were residual multifocal defects in the liver neither hepatic resection nor liver transplantation were considered safe or appropriate. 6.5 years after completion of chemotherapy and now aged 8.5 years the child is in normal health and at school with normal liver size, serum AFP levels and chest imaging.
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- 2006
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4. The Nikolas Symposia and histiocytosis
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Jon Pritchard, Peter Beverley, R. Maarten Egeler, and Robert J. Arceci
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Histiocytosis ,medicine.medical_specialty ,Langerhans cell histiocytosis ,Applied Mathematics ,General Mathematics ,Histiocytoses ,Immunology ,medicine ,Disease ,Biology ,medicine.disease ,Dermatology ,Histiocyte - Abstract
Histiocytoses are a group of rare diseases that involve histiocytes (literally tissue cells (Greek), but in reality tissue-resident macrophages and dendritic cells), which are derived from bone-marrow stem cells. Histiocytoses pose problems similar to those of other rare diseases of childhood. Individual physicians see few cases, disease material is hard to collect and families suffer from lack of information and understanding. In this article, we describe how a series of 'think tank' meetings, the Nikolas Symposia, which have concentrated on Langerhans cell histiocytosis, have furthered our understanding of this enigmatic disease.
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- 2005
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5. Phase II study of high-dose cyclophosphamide in relapsing and/or resistant hepatoblastoma in children: a study from the SIOPEL group
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Margaret Childs, Giorgio Perilongo, Laurence Brugières, Jon Pritchard, Marcello Scopinaro, Walter Daniel Cacciavillano, Penelope Brock, Elisabeth Shafford, and Rudolf Mailbach
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Adult ,Hepatoblastoma ,Male ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Cyclophosphamide ,Phases of clinical research ,Gastroenterology ,Carboplatin ,chemistry.chemical_compound ,Stable Disease ,Refractory ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Child ,Antineoplastic Agents, Alkylating ,business.industry ,Liver Neoplasms ,Middle Aged ,medicine.disease ,Nitrogen mustard ,Surgery ,Clinical trial ,Treatment Outcome ,Oncology ,chemistry ,Doxorubicin ,Child, Preschool ,Female ,Cisplatin ,business ,Progressive disease ,medicine.drug - Abstract
The study sought to evaluate the response to cyclophosphamide (CPM) in hepatoblastoma (HB). Patients with a refractory or relapsing HB after first-line therapy as per SIOPEL 2 and 3 protocols were eligible. All patients were to receive two courses of CPM 2 g/m(2) on days 1 and 2 at 3-week intervals. Eighteen patients were included; 17 were evaluable for response. Prior treatment was cisplatinum alone (1 patient) or cisplatinum-carboplatin-doxorubicin (17 patients). The disease status at the beginning of CPM was: progressive during first-line treatment (10 patients), persistent unresectable disease at the end of the protocol (2 patients), relapse (6 patients). Tumour response was partial response (1 patient), stable disease (1 patient), progressive disease (15 patients) and not evaluable in one. All patients died, 17 of progressive disease and one of surgery complications. The low response rate (1/17) led the SIOPEL group to conclude that single-agent CPM is not effective for the treatment of relapsing or refractory HB.
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- 2004
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6. Histiocyte disorders
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Jan Inge Henter, Carlo Tondini, and Jon Pritchard
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Histiocytosis, Langerhans-Cell ,Histiocytosis, Non-Langerhans-Cell ,Oncology ,Humans ,Hematology ,Histiocytosis, Sinus - Published
- 2004
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7. Outcome of patients with stage III or inoperable WT treated on the second United Kingdom WT protocol (UKWT2); A United Kingdom Children's Cancer Study Group (UKCCSG) study
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J. Imeson, Gordan M. Vujanic, Richard Grundy, Helen Middleton, H.B. Marsden, Anna Kelsey, Jon Pritchard, Roger E. Taylor, and C. Hutton
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Clear-cell sarcoma of the kidney ,Vincristine ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Wilms Tumor ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Stage (cooking) ,Child ,Chemotherapy ,business.industry ,Wilms' tumor ,Hematology ,medicine.disease ,Survival Analysis ,Kidney Neoplasms ,United Kingdom ,Nephrectomy ,Surgery ,Radiation therapy ,Treatment Outcome ,Oncology ,Doxorubicin ,Pediatrics, Perinatology and Child Health ,Dactinomycin ,Radiotherapy, Adjuvant ,Sarcoma, Clear Cell ,business ,Kidney disease ,medicine.drug - Abstract
Background The aims of UKWT2 included consolidating the results for stage III patients obtained in UKWT1 and improving the outcome for patients with inoperable tumours by giving vincristine, actinomycin-D and doxorubicin in an intensive schedule (Intensive AVA). Procedure The second UK WT trial (UKWT2) ran between July 1986 and September 1991 accruing 448 patients. One hundred and six patients were diagnosed and treated for stage III disease. Six had clear cell sarcoma of the kidney (CCSK) and seven had rhabdoid tumours of the kidney (RTK) and are analysed separately. One other patient was excluded from overall analysis. Ninety-two patients were followed for a median of 115 months. Seventy-five received standard chemotherapy and abdominal radiotherapy according to protocol. Seventeen had stage III disease at immediate nephrectomy, but radiotherapy was omitted by physician choice. Thirty-three patients had inoperable disease at diagnosis and received pre-nephrectomy chemotherapy. Results Overall survival (OS) at 4 years for stage III favourable histology (FH) patients receiving abdominal RT was 83% (CI: 73–89). For children with stage III disease in whom RT was omitted the OS was 82% (CI: 59–97) and for inoperable disease 94% (CI: 78–98). The overall and event-free survival (EFS) of children with stage III CCSK was 100% and was achieved with the majority of patients not receiving radiotherapy (CI: 48–100). Three of seven children with RTK are alive EFS and OS 43% (CI: 10–73). For patients treated by abdominal radiotherapy the overall local control rate was 94.4% (CI: 86.4–98.5*%), 96.7% (CI: 88.5–99.6%) for flank RT and 83.3% (51.6–98.0%) for whole abdominal radiotherapy (WRT). Conclusions The outcome for stage III FH disease was similar to that reported for UKWT1 and NWTS-3. The combination of abdominal RT together with 3-drug chemotherapy achieves a high abdominal tumour control rate. Flank RT is probably sufficient for localised tumour rupture. The high cure rates for children in this trial with ‘inoperable disease’ suggests that treatment should be modified according to their post-chemotherapy stage in order to avoid over-treatment. The high OS for stage III CCSK on this protocol suggests that treatment duration could be curtailed and the role of RT reviewed, though the numbers are small. The prognosis for older children with RTK seems to be better than for younger children although larger studies are required to confirm this. © 2003 Wiley-Liss, Inc.
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- 2004
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8. Risk-adapted treatment for childhood hepatoblastoma
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Rudolf Maibach, Giorgio Perilongo, Penelope Brock, Jon Pritchard, Doron Aronson, Piotr Czauderna, Margaret Childs, C.R. Staalman, Laurence Brugières, R. Rondelli, Marcelo Scopinaro, E. Shafford, J.B. Otte, Jack Plaschkes, and G. MacKinlay
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Cisplatin ,Cancer Research ,Hepatoblastoma ,Chemotherapy ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Liver transplantation ,medicine.disease ,Gastroenterology ,Carboplatin ,Surgery ,chemistry.chemical_compound ,Oncology ,chemistry ,Internal medicine ,Toxicity ,medicine ,Doxorubicin ,Risk factor ,business ,medicine.drug - Abstract
SIOPEL 2 was a pilot study designed to test the efficacy and toxicity of two chemotherapy (CT) regimens, one for patients with hepatoblastoma (HB) confined to the liver and involving no more than three hepatic sectors ('standard-risk (SR) HB'), and one for those with HB extending into all four sectors and/or with lung metastases or intra-abdominal extra hepatic spread 'high-risk (HR) HB'. SR-HB patients were treated with four courses of cisplatin (CDDP), at a dose of 80 mg/m(2) every 14 days, delayed surgery, and then two more similar CDDP courses. HR-HB patients were given CDDP alternating every 14 days with carboplatin (CARBO), 500 mg/m(2), and doxorubicin (DOXO), 60 mg/m(2). Two courses of CARBO/DOXO and one of CDDP were given postoperatively. Between October 1995 and May 1998, 77 SR-HB (10 of whom were actually treated with the HR protocol) and 58 HR-HB patients were registered and all 135 could be evaluated. Response rates for the entire SR-HB and HR-HB groups were 90% (95% CI 80-96%) and 78% (95% CI 65-87%). and resection rates were 97% (95% CI 87-99%) and 67% (95% CI 54-79%) including several children undergoing liver transplantation. For SR-HB patients, 3-year overall and progression-free survivals were 91% (+/-7%) and 89% (+/-7%) and for the HR-HB group 53% (+/-13%) and 48% (+/-13%), respectively. The short-term toxicity of these regimens was acceptable, with no toxic deaths. A treatment strategy based on CDDP monotherapy and surgery thus appears effective in SR-HB but, despite CT intensification, only half of the HR-HB patients are long-term survivors. For SR-HB patients, the efficacy of CDDP monotherapy and the CDDP/DOXO ('PLADO') combination are now being compared in a prospective randomied trial (SIOPEL 3). (C) 2003 Elsevier Ltd. All rights reserved.
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- 2004
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9. Cognitive Outcome of Long-Term Survivors of Multisystem Langerhans Cell Histiocytosis: A Single-Institution, Cross-Sectional Study
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Leasha Lillywhite, Jon Pritchard, Louise Parry, Faraneh Vargha-Khadem, Claire Chapman, and Vasanta Nanduri
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Male ,Cancer Research ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Intelligence ,Population ,Pilot Projects ,Neuropsychological Tests ,Langerhans cell histiocytosis ,Central Nervous System Diseases ,Memory ,Cerebellum ,medicine ,Humans ,Learning ,Psychiatry ,education ,Language Disorders ,education.field_of_study ,Intelligence quotient ,business.industry ,Cognitive disorder ,Cognition ,medicine.disease ,Magnetic Resonance Imaging ,Histiocytosis, Langerhans-Cell ,Histiocytosis ,Cross-Sectional Studies ,Oncology ,El Niño ,Cohort ,Female ,Cognition Disorders ,business ,Follow-Up Studies - Abstract
Purpose: Damage to the CNS, including the cerebellum, and to the hypothalamopituitary axis, is documented in Langerhans cell histiocytosis (LCH). Neuropsychologic deficits have been recognized, but this is the first study in which cognitive function has been systematically assessed in a cohort of patients. Patients and Methods: Twenty-eight long-term survivors of multisystem LCH (mean age, 15.1 years) were investigated for intelligence, memory and learning, language, and academic attainments. Results: The mean intelligence quotient (IQ) of the entire group was not significantly different from the mean of the population (ie, mean ± SD, 100 ± 1), but there were wide ranges (Full-Scale IQ [FSIQ]: mean, 93.6; range, 61.7 to 134; Performance IQ [PIQ]: mean, 92.2; range, 46 to 136; and Verbal IQ [VIQ]: mean, 93.7; range, 64.2 to 126). CNS involvement was a significant risk factor for lower scores, but sex, diabetes insipidus, and cranial radiotherapy were not. The CNS group had lower VIQ, PIQ, and FSIQ than patients with no CNS involvement (no CNS group: mean ± SD FSIQ, 102.3 ± 15.6; CNS group: mean ± SD FSIQ, 73.6 ± 7.7; P < .001). A similar pattern of results was obtained for all other cognitive measures. Even when effects of reduction in FSIQ were taken into account, specific deficits were found in patients in the CNS group. Conclusion: Long-term survivors of multisystem LCH, particularly patients with CNS involvement, may develop significant cognitive deficits. All patients should have formal, repeated neuropsychologic assessment as part of long-term follow-up, which will enable abnormalities to be detected early so that appropriate supportive measures can be offered.
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- 2003
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10. Orthotopic liver transplantation for unresectable hepatoblastoma
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Jon Pritchard, Anil Dhawan, Paolo Muiesan, A Baker, Giorgina-Mieli Vergani, Nigel Heaton, Parthi Srinivasan, Mohamed Rela, and John McCall
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Hepatoblastoma ,medicine.medical_specialty ,Lung Neoplasms ,Time Factors ,Adolescent ,medicine.medical_treatment ,Population ,Liver transplantation ,Lymphocytes, Tumor-Infiltrating ,medicine ,Humans ,Child ,education ,Survival rate ,Neoplasm Staging ,Porta hepatis ,Transplantation ,education.field_of_study ,business.industry ,Graft Survival ,Liver Neoplasms ,medicine.disease ,Primary tumor ,Liver Transplantation ,Surgery ,Survival Rate ,Regimen ,Treatment Outcome ,medicine.anatomical_structure ,Child, Preschool ,business - Abstract
Background The outcome of treatment for advanced hepatoblastoma has recently improved after the introduction of preoperative or pre- and postoperative cisplatin-containing chemotherapy combined with complete surgical excision. The role of liver transplantation in a population of patients who have received this regimen has not been clearly defined. Methods Orthotopic liver transplantation (OLT) was performed in 13 children, aged 5 months to 11 years (median 27 months), who were assessed with unresectable hepatoblastoma, and whose pretreatment extent-of-disease was based on radiologic findings of group III (n=11) and group IV (n=2). One child with a multifocal tumor showed pulmonary metastases at presentation, but, according to radiologic studies, the deposits resolved with chemotherapy before liver transplantation. One other child showed exophytic extension of the primary tumor infiltrating the porta hepatis and body of the pancreas. All 13 patients received preoperative chemotherapy to reduce the size of the primary tumor(s) and to treat metastatic spread. Results Twelve children underwent elective OLT; all are alive and show normal graft function at a mean follow-up of 33 months (range 1-108). One child shows evidence of recurrent disease in the form of pulmonary metastases. One child underwent emergency OLT for acute liver failure after (incomplete) extended right hepatectomy and died from respiratory failure, with no evidence of recurrent tumor 3 weeks posttransplant. Conclusions Liver transplantation is an effective treatment for unresectable unifocal or multifocal hepatoblastoma confined to the liver. A multidisciplinary approach to the management of hepatoblastoma, with thoughtful collaboration between pediatric oncologists, hepatologists, and liver surgeons, is essential.
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- 2002
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11. Role of Chest Computed Tomography at Diagnosis in the Management of Wilms’ Tumor: A Study by the United Kingdom Children’s Cancer Study Group
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Catherine M. Owens, P. A. Veys, C. Dicks-Mireaux, Jon Pritchard, J. Imeson, and Gill Levitt
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Male ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Wilms Tumor ,Metastasis ,Predictive Value of Tests ,Recurrence ,Risk Factors ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Stage (cooking) ,Child ,Neoplasm Staging ,Retrospective Studies ,business.industry ,Infant, Newborn ,Infant ,Cancer ,Retrospective cohort study ,Combination chemotherapy ,Wilms' tumor ,Prognosis ,medicine.disease ,Antineoplastic Agents, Phytogenic ,Kidney Neoplasms ,Surgery ,Oncology ,Vincristine ,Child, Preschool ,Predictive value of tests ,Female ,Radiology ,Tomography, X-Ray Computed ,business ,Kidney disease - Abstract
PURPOSE: This study sought to determine whether the identification of minimal pulmonary metastatic disease by chest computed tomography (CT) performed at diagnosis in patients with Wilms’ tumor and normal chest x-rays (CXR) could predict a subgroup of children at increased risk of pulmonary relapse. PATIENTS AND METHODS: A retrospective analysis was carried out of the records of 449 children entered onto the United Kingdom Childrens’ Cancer Study Group Second Wilms’ Tumor Study between July 1986 and September 1991. The imaging protocol did not stipulate chest CT at diagnosis, but 141 children who had normal frontal and lateral CXRs and a chest CT scan performed at diagnosis were eligible for analysis. After surgery, children with stage I Wilms’ tumor received single-agent chemotherapy (vincristine), whereas children with stages II, III, and bilateral Wilms’ tumor received combination chemotherapy. Most children with stage III tumors were also treated with abdominal radiotherapy (20 Gy). RESULTS: In 31 patients (22%), pulmonary nodules were visible on chest CT; eight experienced relapse, four (15%) in the lungs. When only stage I patients were analyzed, there was a significant difference between the pulmonary relapse rate of 43% (three of seven) in the CT-positive group and 10% (five of 48) in the CT-negative group (P = .02). Four of eight patients with stage I disease with pulmonary relapse died. CONCLUSION: CT seemed to identify a subgroup of stage I patients who were at increased risk of pulmonary relapse. These children had received only single-agent chemotherapy. A prospective randomized trial is needed to clarify whether these children would benefit from combination chemotherapy.
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- 2002
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12. Response Without Shrinkage in Bilateral Wilms Tumor: Significance of Rhabdomyomatous Histology
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Patrick G. Duffy, Olga Slater, Kieran McHugh, Jon Pritchard, and John Anderson
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Adult ,Male ,medicine.medical_specialty ,Pathology ,Adolescent ,medicine.medical_treatment ,Rhabdomyoma ,Wilms Tumor ,Disease-Free Survival ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Child ,Survival rate ,Retrospective Studies ,Bilateral Wilms Tumor ,Chemotherapy ,business.industry ,Histology ,Wilms' tumor ,Hematology ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Kidney Neoplasms ,Survival Rate ,Oncology ,Pediatrics, Perinatology and Child Health ,Female ,Histopathology ,business ,Kidney disease - Abstract
To test the hypothesis that poor response to chemotherapy in patients with bilateral Wilms tumor may be associated with the appearance of rhabdomyomatous histology, suggesting a differentiation response.Twenty-six patients with bilateral Wilms tumor were treated at the authors' hospital between 1985 and 1995. Radiologic response to presurgical chemotherapy was assessed, and postsurgery histology was reviewed.There was a significant association between rhabdomyomatous differentiation in postchemotherapy surgical specimens and poor radiologic response. Poor response did not, however, necessarily mean poor outcome: of 11 patients with rhabdomyomatous differentiation, 7 are alive and disease-free, 2 died of complications, and only 2 died of uncontrolled Wilms tumor.Rhabdomyomatous differentiation in postchemotherapy bilateral Wilms tumor is associated with poor radiologic response. This observation may indicate a differentiation response rather than an absolute failure of response to chemotherapy. Clinical measures other than tumor volume are needed to distinguish between tumors that respond to chemotherapy but do not shrink, and those that genuinely do not respond.
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- 2002
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13. Juvenile xanthogranuloma as a sequel to Langerhans cell histiocytosis: a report of three cases
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M. Malone, Peter H. Hoeger, C. Diaz, John I. Harper, and Jon Pritchard
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Cell type ,Pathology ,medicine.medical_specialty ,Juvenile xanthogranuloma ,business.industry ,Dermatology ,medicine.disease ,Histiocytosis ,Cutaneous Involvement ,Langerhans cell histiocytosis ,Touton giant cell ,medicine ,business ,Histiocyte - Abstract
We report three children who had multisystem Langerhans cell histiocytosis (LCH) with cutaneous involvement and subsequently developed juvenile xanthogranuloma (JXG). JXG appeared 3--6 years after the initial manifestation of LCH. JXG lesions, which presented as yellowish papules, revealed typical Touton giant cells and were factor XIIIa positive but S100 and CD1a negative. Non-LCH histiocyte disorders, such as JXG, are known to occur as a reaction to a variety of external stimuli such as infection and trauma. It is therefore conceivable that the inflammatory reaction associated with LCH may have precipitated the development of JXG in our patients. Alternatively, one could speculate that this association might be due to a common histogenetic precursor of the cell types involved.
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- 2001
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14. A randomized trial of treatment for multisystem Langerhans’ cell histiocytosis
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Jörg Michaelis, Stacy Nicholson, Maurizio Aricò, Stephan Ladisch, Ulrike Pötschger, Nicole Grois, Valerie Broadbent, Åke Jakobson, Diane M. Komp, Adriana Ceci, Jon Pritchard, and Helmut Gadner
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medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Adult Langerhans Cell Histiocytosis ,Vinblastine ,Methylprednisolone ,Risk Assessment ,Gastroenterology ,Langerhans cell histiocytosis ,Internal medicine ,medicine ,Humans ,Child ,Etoposide ,Chemotherapy ,business.industry ,medicine.disease ,Survival Analysis ,Surgery ,Histiocytosis, Langerhans-Cell ,Histiocytosis ,Treatment Outcome ,Pediatrics, Perinatology and Child Health ,Toxicity ,Drug Therapy, Combination ,business ,medicine.drug - Abstract
Objective: To compare 2 active agents, vinblastine and etoposide, in the treatment of multisystem Langerhans' cell histiocytosis (LCH) in an international randomized study. Study design: One hundred forty-three untreated patients were randomly assigned to receive 24 weeks of vinblastine (6 mg/m 2 , given intravenously every week) or etoposide (150 mg/m 2 /d, given intravenously for 3 days every 3 weeks), and a single initial dose of corticosteroids. Results: Vinblastine and etoposide were equivalent ( P ≥.2) in all respects: response at week 6 (57% and 49%); response at the last evaluation (58% and 69%); toxicity (47% and 58%); and probability of survival (76% and 83%), of disease reactivation (61% and 55%), and of developing permanent consequences (39% and 51%) including diabetes insipidus (22% and 23%). LCH reactivations were usually mild, as was toxicity. All children ≥2 years old without risk organ involvement (liver, lungs, hematopoietic system, or spleen) survived. With such involvement, lack of rapid (within 6 weeks) response was identified as a new prognostic indicator, predicting a high (66%) mortality rate. Conclusions: Vinblastine and etoposide, with one dose of corticosteroids, are equally effective treatments for multisystem LCH, but patients who do not respond within 6 weeks are at increased risk for treatment failure and may require different therapy. (J Pediatr 2001;138:728-34)
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- 2001
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15. Late relapse and prognosis for neuroblastoma patients surviving 5 years or more: A report from the European Neuroblastoma Study Group ?Survey?
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Simon Cotterill, A. D. J. Pearson, J.A. Kohler, A.B.M. Foot, and Jon Pritchard
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Cancer Research ,Pediatrics ,medicine.medical_specialty ,business.industry ,Disease ,medicine.disease ,Clinical trial ,Oncology ,Relative risk ,Neuroblastoma ,Pediatrics, Perinatology and Child Health ,medicine ,Progression-free survival ,Stage (cooking) ,business ,Late Relapse ,Progressive disease - Abstract
Background and Procedure Most deaths from neuroblastoma occur within 2 years of diagnosis but there have been several anecdotal reports of relapse and death after much longer periods of follow up. In order to investigate and quantify the risk of late events we analysed data for patients registered with the European Neuroblastoma Study Group between 1982 and 1990. Out of a total of 1,277 children registered, 427 were alive with follow-up beyond 5 years from diagnosis (median follow-up of 8.8 years, range 5–14 years). Of these 406 were in remission with no prior recurrence, 16 were in remission having experienced a relapse prior to 5 years, and 5 were alive with progressive disease. Results For the 406 patients in remission with no prior relapse the 10 year progression free survival (PFS) was 96% (CI 94–98). For those aged over 1 year with stage 4 disease at diagnosis 10 year PFS was 88% (CI 79–96) compared to 98% (CI 97–99) for other patients combined, P 1 yr with stage 4 disease at diagnosis (relative risk 10.5, P < 0.001) and prior relapse (RR 4.2, P = 0.01). Conclusions The results of this study emphasise the importance of long-term follow-up of patients and the need for late monitoring of clinical trials in children with neuroblastoma. They also provide a baseline for comparison with future and hopefully more effective treatment programmes. Med. Pediatr. Oncol. 36:235–238, 2001. © 2001 Wiley-Liss, Inc.
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- 2001
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16. Cisplatin, Doxorubicin, and Delayed Surgery for Childhood Hepatoblastoma: A Successful Approach—Results of the First Prospective Study of the International Society of Pediatric Oncology
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Jon Pritchard, Giorgio Perilongo, Jean W. Keeling, Jack Plaschkes, Penelope Brock, Julia Brown, Claire Dicks-Mireaux, E. Shafford, Angela Phillips, and Anton Vos
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Hepatoblastoma ,Male ,Cancer Research ,medicine.medical_specialty ,Liver tumor ,medicine.medical_treatment ,Antineoplastic Combined Chemotherapy Protocols ,Preoperative Care ,medicine ,Humans ,Doxorubicin ,Prospective Studies ,Child ,Prospective cohort study ,Survival rate ,Cisplatin ,Chemotherapy ,business.industry ,Liver Neoplasms ,Infant, Newborn ,Infant ,medicine.disease ,Combined Modality Therapy ,Primary tumor ,Surgery ,Oncology ,Child, Preschool ,Female ,alpha-Fetoproteins ,business ,medicine.drug - Abstract
PURPOSE: Hepatoblastoma (HB) is a rare malignant liver tumor which occurs almost exclusively in childhood. In the 1970s, survival was approximately 20% to 30%. Since the introduction of cisplatin (PLA) and doxorubicin (DO) into the chemotherapy regimens used to treat these patients, the survival rate has improved dramatically. In most recent studies, primary surgery preceded chemotherapy. In this study by the liver group of the International Society of Pediatric Oncology the aim was to improve survival and reduce operative morbidity and mortality by using preoperative chemotherapy. PATIENTS AND METHODS: After biopsy and assessment of pretreatment extent of disease all patients were treated with continuous 24-hour intravenous infusion of PLA 80 mg/m2 followed by DO 60 mg/m2 over 48 hours (PLADO). After four courses of this chemotherapy, patients were reassessed. Where possible, the primary tumor was resected and treatment completed with two more courses of chemotherapy. RESULTS: One hundred fifty-four patients were registered in the study, and 138 received preoperative chemotherapy. One hundred thirteen (82%) showed a partial response with tumor shrinkage and serial decrease of serum alpha-fetoprotein levels. One hundred fifteen patients had delayed surgery, and 106 (including six with liver transplants) had complete resection of primary tumor. Five-year event-free survival was 66%, and overall survival was 75%. CONCLUSION: This study demonstrates that international collaboration on a large scale is feasible. The toxicity of chemotherapy and morbidity of surgery were acceptable and the overall survival gratifyingly high. We now regard PLADO chemotherapy and delayed surgery to be the best available treatment for children with HB. Other treatment programs should be measured against this standard.
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- 2000
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17. Growth and endocrine disorders in multisystem Langerhans' cell histiocytosis
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Jon Pritchard, V. R. Nanduri, Richard Stanhope, and P. Bareille
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Chemotherapy ,medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,medicine.disease ,Growth hormone deficiency ,Histiocytosis ,Endocrinology ,medicine.anatomical_structure ,Langerhans cell histiocytosis ,Anterior pituitary ,Internal medicine ,Diabetes insipidus ,medicine ,Endocrine system ,Complication ,business - Abstract
INTRODUCTION Langerhans' cell histiocytosis is a rare disorder, with diabetes insipidus occurring in up to half of patients. Causes of growth failure include the illness itself, treatments used and growth hormone insufficiency. PATIENTS AND METHODS We identified all patients with an endocrinopathy secondary to Langerhans' cell histiocytosis (LCH). Growth data were analysed from all patients with multisystem involvement. RESULTS Of 144 patients with multisystem LCH, 50 had an endocrinopathy, 49 of whom had diabetes insipidus. Growth hormone insufficiency (GHI) was present in 21 patients, seven of whom had other anterior pituitary deficiencies as well (gonadotrophin deficiency + GHI n = 2, gonadotrophin deficiency + TSH deficiency + GHI n = 2, panhypopituitarism n = 3). GH insufficiency, the development of which appeared to be independent of pituitary radiation, occurred at a median age of 8.3 years (4.7–18 years) and at a median interval of 3.5 years (0–11.8 years) after diagnosis of LCH. The median height SDS at diagnosis of growth hormone insufficiency was −2.9. Thirteen of the patients with growth hormone insufficiency attained final height with a median height SDS of −1.2. The final height SDS of 15 patients without GH insufficiency was closer to target height SDS, but not statistically different from that of the GH insufficient group. CONCLUSIONS GH therapy significantly improves growth in GH insufficient patients with Langerhans' cell histiocytosis. Early institution of GH therapy may further improve height outcome. However, most children with Langerhans' cell histiocytosis regardless of endocrine function, failed to reach target height.
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- 2000
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18. The treatment of Wilms' tumour: results of the United Kingdom Children's Cancer Study Group (UKCCSG) second Wilms' tumour study
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A Kelsey, Brian D. Marsden, P H Morris Jones, Rosemary S. Shannon, Roger E. Taylor, Helen Middleton, Jon Pritchard, Chris Mitchell, Peter Gornall, Gordan M. Vujanic, J. Imeson, and C Owens
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Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Clear-cell sarcoma of the kidney ,Time Factors ,Adolescent ,Wilms’ ,medicine.medical_treatment ,chemotherapy ,Wilms Tumor ,Disease-Free Survival ,Internal medicine ,medicine ,Humans ,childhood cancer ,Stage (cooking) ,Child ,Rhabdoid Tumor ,radiotherapy ,treatment ,tumour ,business.industry ,Infant, Newborn ,Infant ,Cancer ,Regular Article ,Wilms' tumor ,medicine.disease ,Kidney Neoplasms ,Nephrectomy ,Surgery ,Radiation therapy ,Vincristine ,Child, Preschool ,Female ,Sarcoma, Clear Cell ,Sarcoma ,business ,Follow-Up Studies ,Kidney disease - Abstract
The aims of the UKW2 study were: (1) to further refine treatment for stage I and II favourable histology (FH) patients; (2) to consolidate the UKW1 results for stage III FH patients; (3) to improve the outlook for patients with inoperable primary tumours and those patients with stage IV and unfavourable histology disease. Treatment consisted of primary nephrectomy, wherever possible, followed by chemotherapy and radiotherapy, as dictated by stage and histology. Treatment was refined successfully for stage I and II FH patients. The 4-year event-free survival for these two groups was 94% and 91%, respectively. Stage III FH patients had a 4-year event free survival of 84%. The outlook for patients with clear cell sarcoma of the kidney is as good as for patients with favourable histology, whilst that for patients with anaplastic or rhabdoid variants remains poor. The outlook for the majority of children with Wilms’ tumour is now excellent. © 2000 Cancer Research Campaign
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- 2000
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19. Basilar invagination as a sequela of multisystem Langerhans’ cell histiocytosis
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Wui Khean Chong, Gill Levitt, Richard Stanhope, Vasanta Nanduri, Jon Pritchard, and J.M. Jarosz
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Adolescent ,Basilar invagination ,Encephalocele ,Cohort Studies ,Langerhans cell histiocytosis ,Cerebellar Diseases ,Platybasia ,Odontoid Process ,otorhinolaryngologic diseases ,medicine ,Humans ,Foramen Magnum ,Longitudinal Studies ,Survivors ,Child ,Foramen magnum ,business.industry ,Occipital bone ,Sequela ,Anatomy ,medicine.disease ,Magnetic Resonance Imaging ,Histiocytosis, Langerhans-Cell ,Histiocytosis ,medicine.anatomical_structure ,Occipital Bone ,Pediatrics, Perinatology and Child Health ,Female ,Bone Diseases ,Abnormality ,business ,Follow-Up Studies - Abstract
We report the presence of basilar invagination, an unexpected and previously undescribed abnormality of the skull base, in 7 of 38 long-term survivors of multisystem Langerhans' cell histiocytosis. The abnormality is acquired, but its pathogenesis is uncertain.
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- 2000
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20. Labyrinthine involvement in Langerhans' cell histiocytosis
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Peter David Phelps, Vasanta Nanduri, Wui Khean Chong, Kusum Sirimanna, C. M. Bailey, and Jon Pritchard
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Pathology ,medicine.medical_specialty ,Hearing Loss, Sensorineural ,Labyrinth Diseases ,Deafness ,Mastoid ,Bony labyrinth ,Langerhans cell histiocytosis ,otorhinolaryngologic diseases ,medicine ,Humans ,Inner ear ,Cochlea ,Vestibular system ,business.industry ,General Medicine ,medicine.disease ,Histiocytosis, Langerhans-Cell ,Histiocytosis ,medicine.anatomical_structure ,Otorhinolaryngology ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Middle ear ,Female ,Sensorineural hearing loss ,sense organs ,business - Abstract
Background: Langerhans' cell histiocytosis, a rare condition caused by the proliferation of abnormal Langerhans' cells (`LCH cells') and an accompanying granulomatous infiltrate, can affect several organs including the ear. External and middle ear involvement are common with a reported incidence as high as 61%. The bony labyrinth is resistant to erosion by the granulation tissue, thereby protecting the cochlea and vestibular structures. Probably for this reason, involvement of the inner ear is rare, with few case reports in the literature. Patients: We report two girls, one with bilateral and the other with unilateral mastoid involvement, in whom there was invasion of the labyrinth. The first girl had `single system' LCH affecting only bone and developed an acute hearing loss due to invasion of the cochlea, while the second had both bone and skin involvement and labyrinthine involvement was diagnosed on imaging prior to the onset of labyrinthine symptoms. Conclusion: Inner ear involvement can lead to permanent deafness, which may be prevented by early institution of treatment. Threatened inner ear involvement requires urgent systemic medical therapy with steroids, possibly combined with chemotherapy.
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- 1998
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21. Diarrhea after resection of advanced abdominal neuroblastoma: A common management problem
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Jon Pritchard, Michele A. Markley, Helen Rees, Edward M. Kiely, and Agostino Pierro
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Diarrhea ,Loperamide ,medicine.medical_specialty ,medicine.medical_treatment ,Neuroblastoma ,Postoperative Complications ,Clinical Protocols ,medicine ,Humans ,Antidiarrheals ,Child ,Retrospective Studies ,Chemotherapy ,business.industry ,Incidence ,Incidence (epidemiology) ,Infant, Newborn ,Infant ,Combined Modality Therapy ,Surgery ,Survival Rate ,Dissection ,medicine.anatomical_structure ,El Niño ,Abdominal Neoplasms ,Child, Preschool ,Abdomen ,medicine.symptom ,Complication ,business ,medicine.drug - Abstract
Background: After resection of advanced abdominal neuroblastoma, children may have persistent postoperative diarrhea. Until recently, the magnitude of this problem had not been appreciated. Methods: To assess the incidence, severity, and management of chronic postoperative diarrhea in these patients, we reviewed the case notes of all children with stage III or IV abdominal and pelvic neuroblastoma who underwent tumor resection in our hospital between January 1985 and September 1996. We classified the severity of diarrhea as follows: mild, less than 3 loose stools per day; moderate, 3 to 5 loose stools per day; and severe, more than 5 loose stools per day and/or urgency, incontinence, or nocturnal diarrhea. Results: Seventy-seven children underwent resection during this period, and 23 (30%) had postoperative diarrhea, classified as mild in 11 patients, moderate in 7, and severe in 5. Dissection around the superior mesenteric and celiac arteries was associated with a significantly higher incidence of diarrhea. Fifteen children (65%) received treatment with loperamide, which reduced but did not abolish symptoms. Twelve children subsequently died of progressive neuroblastoma. Of the 11 surviving children (mean duration of follow-up, 8.4 years), 8 have persistent loose stools. Conclusions: Diarrhea, probably resulting from disruption of the autonomic nerve supply to the gut during clearance of tumor from the major vessels of the retroperitoneum, is common after resection of advanced abdominal neuroblastoma. Many children require long-term treatment to slow intestinal peristalsis, and a few have severe and unremitting diarrhea. More effective medical management of this complication is needed. (Surgery 1998;123:568-72.)
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- 1998
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22. CONTROVERSIES AND NEW APPROACHES TO TREATMENT OF LANGERHANS CELL HISTIOCYTOSIS
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Malcolm K. Brenner, Jon Pritchard, and Robert J. Arceci
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business.industry ,medicine.medical_treatment ,Genetic Therapy ,Hematology ,Immunotherapy ,medicine.disease ,Bone and Bones ,Genetic therapy ,Histiocytosis, Langerhans-Cell ,Oncology ,Langerhans cell histiocytosis ,Immunology ,medicine ,Humans ,Treatment strategy ,Bone Diseases ,business - Abstract
There continues to be genuine ambivalence as to whether Langerhans cell histiocytosis (LCH) is a primary neoplastic or immuno-dysregulatory disorder. Treatment strategies have moved from one camp to the other depending upon the most current alleged successes or failures. This has been particularly true for patients who fall outside of the sphere where treatment is minimal or where known treatment approaches are clearly beneficial. However, there is growing evidence that LCH is both the result of clonal proliferation of Langerhans cells and the immunologic consequence of increased cellular activation. This new knowledge should be the basis for the development of new therapeutic approaches for patients with LCH and its complications.
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- 1998
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23. Multivariate analysis of risk factors in stage 4 neuroblastoma patients over the age of one year treated with megatherapy and stem-cell transplantation: a report from the European Bone Marrow Transplantation Solid Tumor Registry
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Adj Pearson, D. Frappaz, Olivier Hartmann, Ross Pinkerton, Ruth Ladenstein, Bernhard Kremens, Helmut Gadner, T Klingebiel, Carole Coze, Alberto Garaventa, Christine Lasset, F Chauvin, Paolo Paolucci, Jean Michon, Jon Pritchard, and T Philip
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Male ,Cancer Research ,medicine.medical_specialty ,Neoplasm, Residual ,Adolescent ,medicine.medical_treatment ,Bone Neoplasms ,Hematopoietic stem cell transplantation ,Neuroblastoma ,Risk Factors ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,Stage (cooking) ,Child ,Survival analysis ,Proportional Hazards Models ,Retrospective Studies ,Chemotherapy ,business.industry ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,Infant ,Induction chemotherapy ,Retrospective cohort study ,Total body irradiation ,Prognosis ,Combined Modality Therapy ,Survival Analysis ,Surgery ,Transplantation ,Oncology ,Child, Preschool ,Multivariate Analysis ,Female ,business - Abstract
PURPOSE The European Bone Marrow Transplantation (EBMT) Solid Tumor Registry (STR) contains detailed information on children with advanced neuroblastoma who, after standard-dose induction chemotherapy and surgery, received myeloablative megatherapy (MGT) followed by stem-cell transplantation (SCT). This data base was analyzed to identify factors that predict event-free survival (EFS). PATIENTS AND METHODS Eligibility criteria were stage IV neuroblastoma, age over 1 year at diagnosis, and no relapse before MGT/SCT. Between February 1978 and July 1992, 549 patients were registered by 36 European transplant centers. The median age at diagnosis was 36 months (range, 13 to 216 months) and the male-female ratio was 1:45. Before MGT, 157 patients were in complete remission (CR), 156 in very good partial remission (VGPR), and 208 in partial remission (PR), whereas 24 had had only a minor response (MR). One hundred ten of 546 patients had undergone two successive MGT procedures. The median observation time was 60 months (range, 12 to 187 months). RESULTS Actuarial EFS is 26% at 5 years. Multivariate analysis by the Cox proportional hazards regression model included 529 patients with complete data sets. After adjustment for treatment duration before MGT and double MGT procedures, two adverse, independent risk factors that influenced EFS were identified: (1) persisting skeletal lesions before MGT as defined by technetium (99TC) scans and/or meta-iodobenzylguanidine (mIBG) scans (P = .004) and (2) persisting bone marrow involvement before MGT (P = .03). CONCLUSION After induction treatment, persisting skeletal disease as defined above and persisting bone marrow involvement may be predictive of a particularly poor outcome. Physicians may consider this an additional important tool to decide the patient's management.
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- 1998
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24. Contemporary classification of histiocytic disorders
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Alfred C. Feller, Jon Pritchard, Lawrence M. Weiss, R. Maarten Egeler, Blaise E. Favara, Göran Elinder, Peter Bucsky, Jan-Inge Henter, Shinsaku Imashuku, Mary V. Gresik, Elaine S. Jaffe, Macro Pauli, Maurizio Aricò, Ron Jaffe, Helmut Gadner, Christian Nezelof, Gritta Janka-Schaub, Stephan Ladisch, and Pediatrics
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Cancer Research ,Pathology ,medicine.medical_specialty ,business.industry ,Juvenile xanthogranuloma ,Large cell ,Dendritic cell ,medicine.disease ,Histiocytosis ,Non-Langerhans cell histiocytosis ,Oncology ,Langerhans cell histiocytosis ,Histiocytoses ,Pediatrics, Perinatology and Child Health ,Immunology ,Medicine ,business ,Histiocyte - Abstract
Pathologists and pediatric hematologist/ oncologists of the World Health Organization's Committee on Histiocytic/Reticulum Cell Proliferations and the Reclassification Working Group of the Histiocyte Society present a classification of the histiocytic disorders that primarily affect children. Nosology, based on the lineage of lesional cells and biological behavior, is related to the ontogeny of histiocytes (macrophages and dendritic cells of the immune system). Dendritic cell-related disorders of varied biological behavior are dominated by Langerhans cell histiocytosis, but separate secondary proliferations of dendritic cells must be differentiated. Juvenile xanthogranuloma represents a disorder of dermal dendrocytes, another dendritic cell of skin. The hemophagocytic syndromes are the most common of the macrophage-related disorders of varied biological behavior. Guidelines for distinguishing the exceedingly rare malignant diseases of histiocytes from large cell lymphomas through the use of a battery of special studies are provided.
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- 1997
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25. Diabetes insipidus associated with Langerhans cell histiocytosis: Is it reversible?
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Valerie Broadbent and Jon Pritchard
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Male ,Cancer Research ,medicine.medical_specialty ,Vasopressin ,Pediatrics ,Urinary system ,urologic and male genital diseases ,Thirst ,Polyuria ,Langerhans cell histiocytosis ,Posterior pituitary ,medicine ,Humans ,Hypoglycemic Agents ,Deamino Arginine Vasopressin ,Child ,business.industry ,Infant ,medicine.disease ,Surgery ,Histiocytosis, Langerhans-Cell ,medicine.anatomical_structure ,Oncology ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Diabetes insipidus ,Female ,medicine.symptom ,business ,Polydipsia ,Diabetes Insipidus ,hormones, hormone substitutes, and hormone antagonists - Abstract
Fourteen of 58 (24%) children with Langerhans cell hisiocytosis (LCH) currently attending the Hospital for Sick Children (London) developed thirst and polyuria during the course of their disease. Three had single-system disease confined to bone, and 11 had multisystem disease. The median age at presentation of LCH was 2 years 0 months, and polyuria/polydipsia developed at a median age of 3 years 9 months (range 1 month before diagnosis of LCH to 4 years after diagnosis). Each child had a water deprivation test with measurement of urinary arginine vasopressin (AVP) to document diabetes insipidus. The doses of 1-desamino-8-D arginine vasopressin (DDAVP) required to control symptoms were compared at diagnosis and at a mean follow-up of 7 years 8 months. Local and systemic treatment was recorded. Ten of 14 children were shown to have "complete" diabetes insipidus, whilest the other four had "partial" diabetes insipidus. Seven children were treated with irradiation. with or without systemic chemotherapy, six with systemic chemotherapy only, and one with DDAVP replacement only. No child, including two with partial diabetes insipidus irradiated within 4 weeks of the onset of symptoms, lost symptoms of polyuria/polydypsia and none was able to discontinue DDAVP replacement. One child treated with Etoposide showed a temporary rise in urinary AVP level to within the normal range but still needed DDAVP to control her symptoms. The mean doses of DDAVP at onset of diabetes insipidus and at follow-up were 9.3 micrograms and 18 micrograms daily, respectively. We conclude that the most appropriate treatment for reversing diabetes insipidus complicating Langerhans cell histiocytosis is yet to be determined. Precise documentation of posterior pituitary dysfunction, including measurement of urinary AVP levels, is essential if the effects of new forms of treatment are to be assessed accurately.
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- 1997
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26. Getting there? Salvage therapy for refractory Langerhans cell histiocytosis in children
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Jon Pritchard and Sheila Weitzman
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Salvage Therapy ,Cancer Research ,Pediatrics ,medicine.medical_specialty ,business.industry ,Salvage therapy ,Disease ,medicine.disease ,Pancytopenia ,Vinblastine ,Natural history ,Histiocytosis, Langerhans-Cell ,Histiocytosis ,Oncology ,Langerhans cell histiocytosis ,Chronic Disease ,medicine ,Humans ,Child ,business ,Histiocyte ,medicine.drug - Abstract
1 Haematopoetic failure is usually defined as pancytopenia or Multisystem Langerhans Cell Histiocytosis (MSLCH) is seen in both adults and children and its natural history varies from a chronic grumbling disease, often leaving permanent sequelae to a rapidly progressive treatment-resistant form. Deaths are usually in infants, in the severe form of LCH once known as Letterer-Siwe disease. In successive paediatric cooperative trials, starting with the early German–Austrian DAL HX-83 and DAL HX-90, through the trials of the International Histiocyte Society LCH-I and LCH-II, all with conscientiously collected data and quality control, the mortality for this group of patients has remained between 15% and 20% [1,2]. In these trials, involvement of so called risk organs (lungs, liver, spleen, and haematopoietic system) predicts a high risk group of patients – 10–20% of the total-with life threatening disease. It became apparent from these studies, and from a review by the French Histiocytosis study group encompassing 348 patients [3], that the response to standard induction therapy with corticosteroids and vinblastine usually judged at 6 weeks from diagnosis, was the single most important prognostic factor. The probability of survival for patients in the LCH-I and II studies who failed to respond after 2 cycles of this therapy, – i.e., at 6 weeks from diagnosis – was only 20–34% [2,4] and was as low as 10% after more intensive DAL induction therapy [1]. It became apparent fairly early, therefore, that children with MS-LCH who failed to respond to therapy should move quickly to a salvage protocol , if mortality
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- 2005
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27. Euthanasia in Severely Ill Newborns
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Jon Pritchard and Dermot M Murphy
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medicine.medical_specialty ,Palliative care ,business.industry ,MEDLINE ,Medicine ,General Medicine ,business ,Intensive care medicine - Published
- 2005
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28. Success of clinical trials in childhood Wilms' tumour around the world
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Jon Pritchard and Kathy Pritchard-Jones
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Clinical Trials as Topic ,Pediatrics ,medicine.medical_specialty ,business.industry ,Wilms tumour ,MEDLINE ,Wilms' tumor ,General Medicine ,medicine.disease ,Combined Modality Therapy ,Wilms Tumor ,Kidney Neoplasms ,Clinical trial ,medicine ,Humans ,Child ,business - Published
- 2004
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29. Conservative surgery in multimodal therapy for pelvic rhabdomyosarcoma in children
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P.G. Duffy, A Atra, K Aitken, H. C. Ward, CD Mitchell, Jon Pritchard, M Boyle, P.G. Ransley, C. Dicks-Mireaux, and P.N. Plowman
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Male ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Biopsy ,medicine.medical_treatment ,Urinary Bladder ,Antineoplastic Combined Chemotherapy Protocols ,Rhabdomyosarcoma ,medicine ,Humans ,Combined Modality Therapy ,Pelvic Neoplasms ,Child ,Radionuclide Imaging ,Urinary bladder ,medicine.diagnostic_test ,business.industry ,Infant ,Multimodal therapy ,Cystoscopy ,medicine.disease ,Surgery ,Radiation therapy ,medicine.anatomical_structure ,Oncology ,Child, Preschool ,Female ,Tomography, X-Ray Computed ,business ,Research Article - Abstract
Twenty-six previously untreated children, median age 3.4 years, with pelvic rhabdomyosarcoma (RMS) were seen between 1983 and 1988. Fourteen were girls. The planned strategy was to conserve pelvic organs, especially the bladder, by using primary chemotherapy, conservative surgery and, in most cases, radiotherapy. With a median follow-up of 71 months (range 34-103 months) overall survival was 73%, with no treatment-related death. The bladder salvage rate of 88% in survivors with bladder base/prostate primaries was much higher than that reported by the United States Intergroup Rhabdomyosarcoma Studies (IRS), though many of the preserved bladders did not function normally. We identified problems with both radiological and histological off-treatment monitoring. The overall accuracy of computerised tomographic (CT) scanning for prediction of tumour recurrence was only 81%, and endoscopic biopsies proved misleading in four of the ten bladder base/prostate patients monitored by serial cystoscopy. We conclude that a higher cure rate can be achieved by using intensive chemotherapy/radiotherapy and conservative surgery to treat children with pelvic RMS. Factors that might contribute to our favourable bladder salvage results, compared with those of the IRS, include (a) the fact that one of two specialist surgeons monitored and operated on all these patients and (b) our increasing awareness, during the study, that post-chemotherapy/radiotherapy histopathology and pelvic CT scan appearances may be misleading. Referral to paediatric centres with special experience of pelvic RMS may help raise the rate of bladder salvage in these children.
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- 1994
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30. Bladder and kidney function after cure of pelvic rhabdomyosarcoma in childhood
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Hc C. Ward, Pg G. Duffy, Jon Pritchard, Ck K. Yeung, and Pg G. Ransley
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Male ,Cancer Research ,medicine.medical_specialty ,Time Factors ,Urinary system ,Urinary Bladder ,Urology ,Kidney ,urologic and male genital diseases ,Prostate Rhabdomyosarcoma ,Rhabdomyosarcoma ,medicine ,Humans ,Pelvic Neoplasms ,Child ,Urinary Tract ,Pelvis ,Upper urinary tract ,Urinary Tract Physiological Phenomena ,Urinary bladder ,business.industry ,Infant ,medicine.disease ,Combined Modality Therapy ,female genital diseases and pregnancy complications ,Urodynamics ,Neck of urinary bladder ,medicine.anatomical_structure ,Oncology ,Child, Preschool ,Female ,business ,Research Article - Abstract
Eleven survivors of pelvic rhabdomyosarcoma underwent bladder function studies and upper urinary tract evaluation at a mean of 6.6 years after completion of therapy, which included a conservative, bladder-sparing surgical policy. Primary tumour sites were: bladder base/prostate, 6; bladder dome, 1; vagina, 2; and pelvic side wall, 2. Seven children (five bladder base/prostate, one vagina and one pelvic side wall tumours) had received irradiation to the pelvis with external beam alone, brachytherapy or both. All seven of these patients had markedly reduced functional bladder capacity (11-48% of mean expected value for age) and abnormal voiding patterns, though bladder compliance was not reduced and bladder emptying was almost complete in five cases. Four of these children also had upper tract dilatation and two required reconstructive bladder surgery because of severe bilateral hydronephrosis. By contrast, each of four children treated without radiotherapy had a normal functional bladder capacity and a normal voiding pattern. all survivors of pelvic rhabdomyosarcoma, especially those who have received radiotherapy, should be carefully monitored for dysfunction of both lower and upper urinary tracts. The frequency-volume voiding chart is a sensitive and easily accomplished method of assessing bladder function in these patients.
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- 1994
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31. Testicular function following the treatment of Hodgkin's disease in childhood
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Piers N. Plowman, Judith E. Kingston, Jon Pritchard, O. B. Eden, JS Malpas, M O Savage, and E. Shafford
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Male ,Cancer Research ,Vincristine ,medicine.medical_specialty ,Adolescent ,Prednisolone ,Urology ,Vinblastine ,Procarbazine ,Male infertility ,Radiotherapy, High-Energy ,Follicle-stimulating hormone ,Basal (phylogenetics) ,Antineoplastic Combined Chemotherapy Protocols ,Testis ,medicine ,Orchidometer ,Humans ,Testosterone ,Spermatogenesis ,Infertility, Male ,business.industry ,Oligospermia ,Luteinizing Hormone ,medicine.disease ,Combined Modality Therapy ,Hodgkin Disease ,Surgery ,Oncology ,Chlorambucil ,Follicle Stimulating Hormone ,business ,Research Article ,medicine.drug - Abstract
Testicular function was studied in 40 males treated in childhood for Hodgkin's disease at St Bartholomew's Hospital, and the Hospital for Sick Children, London, between 1971-1985. All patients were 16 years or over at evaluation, and off treatment more than 6 years. Basal FSH, LH and testosterone levels were measured. Testicular size was measured using a Prader orchidometer, and all patients were offered a seminal analysis. Twenty-eight patients were treated with chemotherapy, usually ChlVPP. Twenty-one also had radiotherapy, five below the diaphragm. Twelve patients were treated with radiotherapy alone (five below the diaphragm). Twenty-six of 28 patients treated with chemotherapy and three of five patients treated with radiotherapy alone below the diaphragm have elevated basal FSH levels, and 18 of these also have elevated basal LH levels. Median testicular volume is 11 ml (range 5-25 ml). Eleven of 13 patients investigated are azoospermic. All patients have normal testosterone levels, and normal secondary sexual characteristics. There is no biochemical evidence of healing of the damaged germinal epithelium with elevated FSH levels persisting up to 17 years from the end of therapy. These results indicate a high incidence of damage to the germinal epithelium in patients treated with ChlVPP chemotherapy and/or radiotherapy below the diaphragm. Appropriate counselling of these patients with regard to their reproductive capabilities is essential.
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- 1993
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32. Renal size and function after cure of Wilms' tumour
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C. Dicks Mireaux, Gill Levitt, Jon Pritchard, E. Yeomans, Judith E. Kingston, and F. Breatnach
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Male ,Cancer Research ,medicine.medical_specialty ,Wilms tumour ,Urology ,Renal function ,Blood Pressure ,urologic and male genital diseases ,Kidney ,Wilms Tumor ,Risk Factors ,Renin ,medicine ,Humans ,Child ,business.industry ,Infant ,Wilms' tumor ,Organ Size ,medicine.disease ,Surgery ,medicine.anatomical_structure ,Oncology ,El Niño ,Child, Preschool ,Female ,Kidney Diseases ,business ,Off Treatment ,Research Article ,Follow-Up Studies ,Glomerular Filtration Rate - Abstract
Now that most patients with Wilms' tumour are cured, it is practicable to study the long-term morbidity of their treatment and use this information to reduce treatment sequelae in the future. In this study we evaluate the size and function of the remaining kidney in 53 survivors of Wilms' tumour with a mean off treatment follow-up of 13 years. There was evidence of renal dysfunction in 17 (32%), including ten (19%) with a low GFR (< 80 ml/min/1.73 m2SA), six (11%) with hypertension and five (9%) with increased urinary albumin excretion. Measurements of renal size showed 'good' renal compensatory hypertrophy in only 55% of patients. 'Good' refers to renal size of more than 2 s.d. above the mean renal length for children with two kidneys. There were no correlations between GFR, renal size, blood pressure, microalbuminuria or type of treatment. However, children less than 24 months at diagnosis and children receiving chemotherapy with radiation doses to remaining kidney of more than 1200 cGy had a worse renal prognosis. Patients whose Wilms' tumour is diagnosed in infancy should have careful long-term follow-up of renal function and size. Older patients may safely be followed up less often, unless their remaining kidney was received > 1200 cGy.
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- 1992
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33. Histiocytosis syndromes in children
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Ayad Atra and Jon Pritchard
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medicine.medical_specialty ,Histiocytosis ,Pathology ,business.industry ,Pediatrics, Perinatology and Child Health ,medicine ,business ,medicine.disease ,Dermatology - Published
- 1992
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34. Pilot study of high-dose vincristine, etoposide, carboplatin and melphalan with autologous bone marrow rescue in advanced neuroblastoma
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Ross Pinkerton, Simon T. Meller, Robin Corbett, Judith E. Kingston, Jon Pritchard, Ian J. Lewis, and T. J. McElwain
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Oncology ,Melphalan ,Cancer Research ,Vincristine ,medicine.medical_specialty ,Chemotherapy ,business.industry ,medicine.medical_treatment ,Induction chemotherapy ,Carboplatin ,Surgery ,Transplantation ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,Internal medicine ,medicine ,Bone marrow ,business ,Etoposide ,medicine.drug - Abstract
The efficacy and toxicity of a high-dose multiagent consolidation regimen, OMEC (vincristine, melphalan, etoposide and carboplatin), with autologous bone marrow rescue was studied in patients with poor-prognosis neuroblastoma. 20 patients were treated with OMEC, 18 after induction chemotherapy and 2 following relapse. All patients received, per m2, vincristine 4 mg, etoposide 1 g, carboplatin 1.0-1.75 g and melphalan 180 mg followed by bone marrow rescue. 4 patients (20%) died of treatment-related complications. Severe gastrointestinal toxicity occurred in all of these patients, and in 75% of patients overall. 1 of 5 patients with evaluable disease achieved complete remission. 13 patients (65%) have relapsed a median of 10 months (range 3-26) after receiving OMEC. Thus, OMEC was not more effective, yet more toxic, than high-dose melphalan given alone, and the use of similar multiagent regimens with overlapping toxicities in advanced neuroblastoma appears inadvisable.
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- 1992
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35. Topical nitrogen mustard: An effective treatment for cutaneous Langerhans cell histiocytosis
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Jon Pritchard, D.J. Atherton, Valerie Broadbent, and Mary P. Sheehan
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Male ,medicine.medical_specialty ,Langerhans cell ,Palliative care ,Administration, Topical ,Skin Diseases ,chemistry.chemical_compound ,Langerhans cell histiocytosis ,medicine ,Humans ,Mechlorethamine ,Adverse effect ,Histiocyte ,Mechlorethamine Hydrochloride ,business.industry ,Remission Induction ,Infant ,medicine.disease ,Dermatology ,Nitrogen mustard ,Surgery ,Solutions ,Histiocytosis, Langerhans-Cell ,medicine.anatomical_structure ,Respiratory failure ,chemistry ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Drug Evaluation ,Female ,Powders ,business - Abstract
In 16 children with multisystem Langerhans cell histiocytosis (mean age 22 months, range 5 to 36 months) severe symptomatic skin involvement was treated with topical nitrogen mustard (mechlorethamine hydrochloride). In each case, rapid clinical improvement occurred within 10 days; subsequent complete healing was observed in 14 children, and partial healing in 2 others in whom treatment was a component of palliative care. Mean duration of treatment was 3.5 months (range 2 to 6 months). Systemic treatment was averted in 11 patients because response to topical therapy was so favorable, but bone marrow or respiratory failure led to a fatal outcome in 5 other patients. Adverse effects were minimal. One patient developed contact allergy to topical nitrogen mustard after 2 years of intermittent therapy, but was successfully desensitized and was then able to continue treatment. We conclude that the topical application of nitrogen mustard is an effective treatment for cutaneous Langerhans cell histiocytosis. Although adverse effects were minimal in the short term, there remains concern about the possibility of long-term cutaneous carcinogenicity.
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- 1991
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36. Partial reversibility of cisplatin nephrotoxicity in children
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Penelope Brock, Dimitri E. Koliouskas, T. Martin Barratt, Jon Pritchard, and Elizabeth Yeomans
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Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Urology ,Renal function ,Blood Pressure ,Kidney ,Nephrotoxicity ,Hypomagnesemia ,Neoplasms ,medicine ,Humans ,Child ,Melphalan ,Cisplatin ,Chemotherapy ,Cumulative dose ,business.industry ,Infant, Newborn ,Infant ,medicine.disease ,Surgery ,Kidney Tubules ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Toxicity ,Female ,business ,Complication ,Follow-Up Studies ,Glomerular Filtration Rate ,medicine.drug - Abstract
To evaluate the long-term renal toxicity of cisplatin, 40 children who had been without treatment at least 18 months (range 18 months to 7 years) were observed. In all the children, glomerular filtration rate (GFR) was estimated from the plasma clearance of chromium 51-labeled ethylenediaminetetraacetic acid, both at the end of treatment and at a median follow-up of 2 years 6 months after treatment was stopped (range 18 months to 7 years). In 21 children, serum magnesium level was also measured at follow-up. Median age at diagnosis was 15 months (range 13 days to 13 years 8 months), and median cumulative doses of cisplatin was 500 mg/m2 (range 120 to 1860 mg/m2). In 22 of 24 children with an end-of-treatment GFR of less than 80 ml/min per 1.73 m2, the median improvement in GFR at follow-up was 22 ml/min per 1.73 m2 (range 2 to 56 ml/min per 1.73 m2). Hypomagnesemia was found in 6 of 21 children and was independent of GFR. No significant correlation was found between improvement in renal function and total cisplatin dose, age, gender, tumor type, or associated nephrotoxic medication. We conclude that most children have some recovery from cisplatin glomerular toxicity, especially if damage is not severe, but that hypomagnesemia may persist.
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- 1991
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37. Wilms' tumour: Pre- and post-chemotherapy CT appearances
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Margaret A Hall-Craggs, Y.Y. Ng, C. Dicks-Mireaux, and Jon Pritchard
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Male ,Vincristine ,medicine.medical_specialty ,medicine.medical_treatment ,Wilms Tumor ,medicine ,Humans ,Combined Modality Therapy ,Radiology, Nuclear Medicine and imaging ,Doxorubicin ,Child ,Retrospective Studies ,Chemotherapy ,business.industry ,Liver Neoplasms ,Infant ,Wilms' tumor ,Retrospective cohort study ,General Medicine ,medicine.disease ,Kidney Neoplasms ,Child, Preschool ,Dactinomycin ,Drug Therapy, Combination ,Female ,sense organs ,Radiology ,Tomography ,Lymph ,Tomography, X-Ray Computed ,business ,medicine.drug - Abstract
Pre-operative chemotherapy is used in our institution for patients with Wilms' Tumours (WT) when surgical 'operability' is in doubt. To date, the computed tomographic (CT) appearances of chemotherapy-induced changes in WT have not been described. We have analysed CT examinations of 18 children undergoing pre-operative chemotherapy to assess the effects of treatment on size, extent and qualitative changes of the tumour. Clinical response to chemotherapy was associated with a reduction in tumour size of at least 50%. Cystic changes were commonly seen within tumours following chemotherapy. CT did not reliably differentiate lymph nodes involved by tumour from those showing only reactive change. Pre-chemotherapy CT scans were incorrect in predicting liver invasion in 4/18 (22%) cases: of these, two were right-sided tumours, and two were bilateral.
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- 1991
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38. Cytogenetic analysis of primitive neuroectodermal tumors
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Marian Malone, Patricia Gorman, Denise Sheer, and Jon Pritchard
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Genetics ,Cancer Research ,medicine.medical_specialty ,Pathology ,Peripheral Primitive Neuroectodermal Tumor ,Cytogenetics ,Chromosomal translocation ,Karyotype ,Biology ,medicine.disease ,medicine ,Tumor type ,Neuroectodermal tumor ,Molecular Biology - Abstract
Cytogenetic analyses on direct and short-term cultures from three peripheral primitive neuroectodermal tumors (PNET) showed only one tumor with the t(11;22)(q24;q12), a translocation reported as characteristic of this tumor type. A second tumor contained rearrangements including apparent deletions of chromosomes 11 and 22 between bands 11q21 and 11qter and between bands 22q11.2 and 22qter, respectively. A third tumor contained two normal copies of 11q but appeared to be monosomic for 22. We consider these findings in light of a survey of the PNET literature.
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- 1991
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39. Cisplatin ototoxicity in children: A practical grading system
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E. C. Yeomans, Penelope Brock, CR Pinkerton, Jon Pritchard, and S C Bellman
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Cancer Research ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Hearing loss ,medicine.medical_treatment ,Age at diagnosis ,Ototoxicity ,medicine ,Humans ,Child ,Hearing Loss, High-Frequency ,Monitoring, Physiologic ,Cisplatin ,Chemotherapy ,Individual susceptibility ,medicine.diagnostic_test ,business.industry ,Infant ,medicine.disease ,Surgery ,Oncology ,El Niño ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Audiometry, Pure-Tone ,medicine.symptom ,Audiometry ,business ,Follow-Up Studies ,Glomerular Filtration Rate ,medicine.drug - Abstract
A long-term follow-up study was carried out to assess ototoxicity in children who had been treated for a malignant tumour with "standard dose" cisplatin (60-100 mg/m2 per course), and were at least 2 years from stopping treatment. The median age at diagnosis was 2 years 2 months (range 1 month to 13.5 years). On the basis of hearing assessment by pure-tone audiometry, a practical grading system of hearing loss from 0 to 4 is proposed. Moderate to severe high-frequency hearing loss (grade 2-4) was found in half the children and 10 require appropriate hearing aids. The risk of developing ototoxicity increased significantly with the cumulative cisplatin dose (P = 0.027), although there was considerable individual susceptibility. Serial follow-up testing, to a median of 4 years after completion of cisplatin treatment, showed no recovery of hearing in any of these children. We suggest careful monitoring of young children by a consultant audiological physician throughout treatment with cisplatin, particularly when doses of 400 mg/m2 and over have been reached. Alternative chemotherapy should be discussed if grade 2 ototoxicity develops.
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- 1991
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40. Use of indomethacin in Langerhans cell histiocytosis
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Valerie Broadbent, Lucy Olliver, Stephanie E. Munn, and Jon Pritchard
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Male ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Prostaglandin Antagonists ,Bone disease ,medicine.medical_treatment ,Indomethacin ,Analgesic ,Prostaglandin ,Bone Neoplasms ,chemistry.chemical_compound ,Indometacin ,Langerhans cell histiocytosis ,Eosinophilic granuloma ,medicine ,Humans ,Child ,Retrospective Studies ,Chemotherapy ,business.industry ,Anti-Inflammatory Agents, Non-Steroidal ,medicine.disease ,Skeleton (computer programming) ,Surgery ,Histiocytosis, Langerhans-Cell ,Treatment Outcome ,Oncology ,chemistry ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Female ,business ,medicine.drug - Abstract
Background Because prostaglandin (PG) E2 has been identified in the bone lesions of Langerhans cell histiocytosis (LCH), we speculated that indomethacin, a potent PG inhibitor, may be useful in patients with symptomatic LCH involving the bony skeleton. Procedure We used indomethacin to treat patients in whom we wanted to avoid steroids or chemotherapy, or in whom these treatments did not provide complete symptom relief. Ten children with bony LCH between 1984 and 1995 were treated; six had single-system bone disease and four had multisystem disease involving the bony skeleton and other organs. Results The dose of indomethacin ranged from 1 to 2.5 mg/kg/day (9–200 mg/day) in divided doses and was given for 1–16 weeks (mean, 6 weeks). Eight patients had a complete response to treatment, defined as complete resolution of symptoms for 4 weeks. One patient was withdrawn from treatment because of concern regarding the potential of indomethacin to induce seizures and a second patient, with suppurative skin lesions overlying a lytic skull defect, did not respond. Conclusions Indomethacin is a useful therapy for LCH involving the bony skeleton and may have a role as first-line treatment in single-system bone disease. Whether it has a specific role in slowing disease progression or merely acts as an analgesic has not yet been established. Med. Pediatr. Oncol. 32:247–249, 1999. © 1999 Wiley-Liss, Inc.
- Published
- 1999
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41. Primary malignant liver tumors in childhood: Assessment of resectability with high-field MR and comparison with CT
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Jon Pritchard, Vergani Gm, J. P. Finn, Howard Er, Margaret A Hall-Craggs, Spitz L, and C. Dicks-Mireaux
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medicine.medical_specialty ,Liver tumor ,Contrast Media ,Hepatic Veins ,Inferior vena cava ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,Prospective cohort study ,Ultrasonography ,Neuroradiology ,medicine.diagnostic_test ,Portal Vein ,business.industry ,Liver Neoplasms ,Ultrasound ,Infant, Newborn ,Infant ,Magnetic resonance imaging ,Image Enhancement ,medicine.disease ,Magnetic Resonance Imaging ,Liver ,medicine.vein ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Signal averaging ,Radiology ,Tomography ,Tomography, X-Ray Computed ,business - Abstract
Nine children (mean age 20 months), with proven primary malignant hepatic tumors have been examined prospectively by high-field magnetic resonance (MR) imaging to assess tumor resectability. All patients had comparative ultrasonography (US), 8 patients had X-Ray computed tomography (CT), and surgical correlation was available in 8 patients. The hepatic and portal veins and the inferior vena cava were visualized in all patients on MR and in 4 of 8 patients on CT. MR accurately defined liver parenchymal involvement in all 8 patients who had surgical exploration. CT underestimated disease in 2 cases, and defined tumour margins less clearly than MR. MR identified abnormal extrahepatic tissue when present, but was unable to distinguish viable tumor from necrotic tumor or reactive nodes. High quality short TR/short TE spin echo images were obtained by combining cardiac triggering and signal averaging. Short TI inversion recovery images demonstrated tumor and lymphadenopathy most clearly. We conclude that MR is the imaging method of choice for the assessment of liver tumor resectability in children.
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- 1990
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42. Clinicopathologic review of twelve children with nephropathy, Wilms tumor, and genital abnormalities (Drash syndrome)
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I. Gordon, Michael J. Dillon, Jon Pritchard, L. Jadresic, T.M. Barratt, J. Leake, D.B. Grant, and R. A. Risdon
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Male ,Denys–Drash syndrome ,Pathology ,medicine.medical_specialty ,Nephrotic Syndrome ,Genitalia, Male ,Kidney ,Wilms Tumor ,Nephropathy ,medicine ,Humans ,Sex organ ,Genitalia ,Child ,Sex Chromosome Aberrations ,Proteinuria ,business.industry ,Infant ,Wilms' tumor ,Genitalia, Female ,Syndrome ,medicine.disease ,Kidney Neoplasms ,Aniridia ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Kidney Failure, Chronic ,Female ,Kidney Diseases ,Abnormality ,medicine.symptom ,business ,Nephrotic syndrome - Abstract
The clinicopathologic and radiologic features of 12 children with complete and incomplete forms of Drash syndrome are reported. Their common denominator was a nephropathy. Four had the full triad, consisting of nephropathy, Wilms tumor, and genital abnormalities; five had nephropathy and genital abnormalities, and three had nephropathy and Wilms tumor. Of the 11 children who had proteinuria, eight had the nephrotic syndrome. Of the 10 whose condition progressed to end-stage renal failure, seven were less than 3 years of age. The histologic features of Wilms tumor were favorable in all seven children, and the tumor was bilateral in three. Of the nine patients who had genital abnormalities, eight had 46, XY karyotype and either ambiguous genitalla (six patients) or normal female phenotype (two). One other patient had a normal 46, XX female karyotype and phenotype but had both mullerian and wolffian structures and a streak ovary. Nine patients had a distinct pelvicaliceal abnormality not previously reported as a feature of this syndrome. Other congenital abnormalities were aniridia, mental retardation, deafness, nystagmus and cleft palate. This syndrome must be considered in any infant with unexplained nephropathy, particularly in young phenotypic female infants and in those children with ambiguous genitalia or Wilms tumor with an early presentation.
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- 1990
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43. Deletion of part of the short arm of chromosome 17 in a congenital fibrosarcoma
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Jon Pritchard, Marian Malone, Patricia Gorman, and Denise Sheer
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Gene Rearrangement ,Leg ,Cancer Research ,Pathology ,medicine.medical_specialty ,Congenital fibrosarcoma ,Fibrosarcoma ,Infant, Newborn ,Soft tissue ,Soft Tissue Neoplasms ,Karyotype ,Biology ,medicine.disease ,Chromosome 17 (human) ,hemic and lymphatic diseases ,Monoclonal ,Immunology ,Genetics ,medicine ,Humans ,Chromosome Deletion ,neoplasms ,Molecular Biology ,Chromosomes, Human, Pair 17 - Abstract
Cytogenetic reports of soft tissue sarcomas in children, other than rhabdomyosarcomas, are rare. We report the second cytogenetic analysis of a congenital fibrosarcoma. The tumor had a monoclonal karyotype of 49,XX,+7,+15,+del(17)(p12).
- Published
- 1990
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44. 'JEB'--a carboplatin based regimen for malignant germ cell tumours in children
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Jon Pritchard, T. J. McElwain, J Levitt, V Broadbent, Anthony Oakhill, Simon T. Meller, CR Pinkerton, M Mott, and A Horwich
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Male ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Organoplatinum Compounds ,Pulmonary toxicity ,medicine.medical_treatment ,Bleomycin ,Gastroenterology ,Carboplatin ,JEB Regimen ,chemistry.chemical_compound ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Child ,Lung ,Etoposide ,Cisplatin ,Chemotherapy ,business.industry ,Infant ,Neoplasms, Germ Cell and Embryonal ,Surgery ,Regimen ,Oncology ,chemistry ,Child, Preschool ,Female ,business ,medicine.drug ,Research Article - Abstract
Between February 1986 and July 1988 a total of 21 children aged 1 to 16 years with malignant germ cell tumours (MGCT), 18 with either metastatic disease or unresectable primary tumour, received the JEB regimen - carboplatin dosage calculated from the EDTA glomerular filtration rate (approximately 600 mg m-2), etoposide 120 mg m-2 daily x 3, and bleomycin 15 mg m-2 weekly. Primary sites were: testis (6), ovary (8), sacrococcyx (4), pineal gland (2) and vagina (1). AFP levels were elevated in 19, beta-HCG in 8. Complete marker response was achieved in 19 out of 19 evaluable patients and complete remission of measurable tumour in 16 out of 19, 12 with chemotherapy alone and 4 with the addition of surgery. A reduction in glomerular filtration rate greater than 10% occurred in 3 of 12 evaluable patients; in none greater than 20%. Sequential audiography was normal in 11 out of 12 evaluated. The regimen was myelosuppressive with WHO grade III or IV myelosuppression occurring in 12 patients. Three patients have relapsed; one with a pineal germinoma who relapsed in the abdomen six months after diagnosis, and two with sacrococcygeal teratomas and lung metastases. Two of these remain in second complete remission after further treatment. There was one death from probable bleomycin pulmonary toxicity. We conclude that this regimen is simple to administer and, apart from myelosuppression, it is well tolerated. It appears to have comparable efficacy to cisplatin-based regimens but with much less nephrotoxicity and ototoxicity and avoids the use of alkylating agents and anthracyclines.
- Published
- 1990
45. Hepatoblastoma with a low serum alpha-fetoprotein level at diagnosis: the SIOPEL group experience
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Jon Pritchard, Maretta De Ioris, Rudolf Maibach, Piotr Czaudzerna, Giorgio Perilongo, Jean W. Keeling, Penelope Brock, Liz Shafford, Arthur Zimmermann, Laurence Brugières, Joszef Zsiros, CCA -Cancer Center Amsterdam, APH - Amsterdam Public Health, and Paediatric Oncology
- Subjects
Hepatoblastoma ,Male ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Low serum alpha-fetoprotein ,CHILDREN ,Disease ,Gastroenterology ,Disease-Free Survival ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Chemotherapy ,business.industry ,Liver Neoplasms ,Infant, Newborn ,Cancer ,Infant ,Histology ,medicine.disease ,Combined Modality Therapy ,Confidence interval ,digestive system diseases ,Surgery ,Treatment Outcome ,Oncology ,Female ,alpha-Fetoproteins ,Alpha-fetoprotein ,business - Abstract
To investigate the characteristics of patients with hepatoblastoma and low serum alpha-fetoprotein (AFP) at diagnosis. Inclusion of all 21 patients accrued onto SIOPEL trials, whose serum AFP was
- Published
- 2007
46. Radiotherapy omitted in the treatment of selected children under 3 years of age with stage III favorable histology Wilms tumor
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Gill Levitt, Mark N. Gaze, Jon Pritchard, Antony Michalski, and A. Pachnis
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Male ,Cancer Research ,Vincristine ,medicine.medical_specialty ,medicine.medical_treatment ,Nephrectomy ,Wilms Tumor ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Stage (cooking) ,Survival rate ,Neoplasm Staging ,Chemotherapy ,business.industry ,Infant ,Wilms' tumor ,medicine.disease ,Combined Modality Therapy ,Kidney Neoplasms ,Surgery ,Radiation therapy ,Oncology ,Doxorubicin ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Dactinomycin ,Female ,business ,Progressive disease ,Kidney disease ,medicine.drug - Abstract
Background. Current treatment of stage III favorable histology (FH) Wilms tumor is surgery, radiotherapy to residual disease, and ''triple'' chemotherapy (vincristine, dactinomycin, and doxorubicin) for 12 months. This study tests the hypothesis that some stage III patients, especially very young children with minimal residual abdominal disease, might be successfully treated without radiotherapy, thereby avoiding the adverse late effects associated with radiotherapy. Procedure. From 1984, radiotherapy was omitted from the treatment of 8 carefully selected children who were younger than 3 years of age at diagnosis with stage III Wilms tumor by virtue of microscopic residual disease after surgery and whose lymph nodes were not involved by tumor. They were followed with bimonthly abdominal ultrasound examinations to assess local control. Results. Follow-up is now from 2 to 12 years (me dian 6 years) and 7 of the 8 children are alive and well with no abdominal recurrence. One child relapsed in the lungs and despite further treatment died of progressive disease. The disease-free survival (DFS) and overall survival (OS) are therefore both 87.5%. Conclusions. The DFS and OS in this admittedly small sample are consistent with the survival rates for stage III FH Wilms tumor in the first United Kingdom Children's Cancer Study Group (UKCCSG), North American (NWTS), and European (SIOP) Wilms Tumor studies. Larger numbers of patients are needed to determine whether or not this treatment approach is generally applicable, but we conclude that some children in this stage III ''substage'' may be treated successfully without radiotherapy. Med. Pediatr. Oncol. 31:150-152, 1998. (C) 1998 Wiley- Liss, Inc
- Published
- 1998
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47. Long term morbidity and health related quality of life after multi-system Langerhans cell histiocytosis
- Author
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Gill Levitt, Vasanta Nanduri, Adam Glaser, and Jon Pritchard
- Subjects
Adult ,Male ,Cancer Research ,Pediatrics ,medicine.medical_specialty ,Activities of daily living ,Adolescent ,Cross-sectional study ,Health Status ,Physical examination ,Langerhans cell histiocytosis ,Quality of life ,Surveys and Questionnaires ,Activities of Daily Living ,medicine ,Humans ,Respiratory function ,Survivors ,Child ,medicine.diagnostic_test ,business.industry ,Infant ,medicine.disease ,Histiocytosis ,Histiocytosis, Langerhans-Cell ,Cross-Sectional Studies ,Oncology ,Child, Preschool ,Quality of Life ,Female ,Audiometry ,business ,Follow-Up Studies - Abstract
Background: Langerhans’ cell histiocytosis, a clonal multisystem disorder, can affect children or adults resulting in long term sequelae. However, the overall morbidity for survivors has not been formally determined. Patients and Methods: We performed a cross-sectional study of 40 unselected long term survivors of childhood multisystem Langerhans cell histiocytosis, involving clinical examination, health–related quality of life assessment, brain imaging, neuropsychometry, endocrine assessment, respiratory function tests and audiometry. A specific ‘morbidity score’ was devised to measure outcome. Results: Seventyfive percent of patients had detectable long term sequelae, hypothalamic-pituitary dysfunction (50%), cognitive dysfunction (20%) and cerebellar involvement (17.5%) being the most common. Half had moderate to severe morbidity, and the worst-affected patients were unable to lead an independent adult life. Health-related quality of life, which correlated well with the morbidity score (p 50% of patients. Conclusion: Organ damage from multisystem Langerhans cell histiocytosis causes long term morbidity extending into adult life. Carefully planned, multidisciplinary follow up is essential to ensure early recognition of problems with appropriate interventions to reduce the impact on patients’ ‘quality of life’.
- Published
- 2006
48. Multiple gastric stromal tumors in a child without syndromic association lacks common KIT or PDGFRalpha mutations
- Author
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Iain D. Penman, Amanda J. McCabe, Maureen J. O'Sullivan, Jon Pritchard, Peter M. Gillett, and Gordon A. MacKinlay
- Subjects
Pathology ,medicine.medical_specialty ,Receptor, Platelet-Derived Growth Factor alpha ,Gastrointestinal Stromal Tumors ,Context (language use) ,Biology ,medicine.disease_cause ,Polymerase Chain Reaction ,Germline ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Germline mutation ,medicine ,Genetic predisposition ,Humans ,Stromal tumor ,Family history ,Child ,Mutation ,030219 obstetrics & reproductive medicine ,GiST ,General Medicine ,Proto-Oncogene Proteins c-kit ,030220 oncology & carcinogenesis ,Pediatrics, Perinatology and Child Health ,Cancer research ,Female - Abstract
A diagnosis of multiple gastric stromal tumors that were nonmetastatic at presentation was made in an 11-year-old girl who presented with hematemesis. Gastrointestinal stromal tumor (GIST) is a rare diagnosis in childhood and reported multiple lesions are generally seen in the context of familial disease, occasionally with syndromic associations. Although there are no reports of genetic mutation in cases of pediatric GIST, very many cases of multiple GISTs investigated on a molecular level have shown germline KIT or platelet-derived growth factor receptor-α mutation; these were familial cases. Despite the negative family history in our patient, the multiplicity of lesions in such a young patient raised concern for a genetic predisposition and prompted extensive molecular workup. Repeat evaluation of distinct aliquots of tumor tissue by polymerase chain amplification followed by sequence analysis of selected coding sequences of KIT and platelet-derived growth factor receptor-α previously shown to harbor mutations in GIST, yielded no evidence of even a somatic mutation. This clinically unique case is discussed in the context of a literature review.
- Published
- 2005
49. Clonal relationship between precursor T-lymphoblastic leukaemia/lymphoma and Langerhans-cell histiocytosis
- Author
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Stephen J. Lauer, Robert J. Arceci, Frank Berthold, Karen P. Mann, Mark Raffeld, Andrew L. Feldman, Elaine S. Jaffe, Jon Pritchard, Bahig M. Shehata, and Carlos R. Abramowsky
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Mediastinal Neoplasms ,Diagnosis, Differential ,Langerhans cell histiocytosis ,hemic and lymphatic diseases ,medicine ,Humans ,Child ,Etoposide ,business.industry ,medicine.disease ,Combined Modality Therapy ,Lymphoma ,Vinblastine ,Leukemia, Lymphoid ,Leukemia ,Histiocytosis ,Histiocytosis, Langerhans-Cell ,Oncology ,Chlormethine ,Child, Preschool ,Prednisolone ,business ,medicine.drug - Abstract
1but the biological basis for this link is unknown. We report two cases of Langerhans-cell histiocytosis arising in the context of precursor T-lymphoblastic leukaemia/lymphoma. The Langerhans-cell histiocytosis cells and the precursor T-lymphoblastic leukaemia/lymphoma cells had identical rearrangements of the gene for T-cell receptor � , confirming a clonal relation between the two neoplastic diseases. In April, 1996, a 5-year-old boy presented with a mediastinal mass and a white-cell count of 2·9� 10 9 /L. Bone-marrow aspiration showed precursor T-cell acute lymphoblastic leukaemia; cerebrospinal fluid was negative. He had a complete response to the BerlinFrankfurt-Munster middle-risk schedule. However, from August, 1998, to October, 1998, he developed multiple penile lesions and a biopsy sample showed Langerhans-cell histiocytosis. Between 1998 and 2002 he received several chemotherapeutic regimens and radiotherapy (total dose 44·8 Gy), without a sustained complete response. Regimens included: etoposide and prednisolone; combinations of topical chlormethine, indometacin, betamethasone-depot, vinblastine, thalidomide, etanercept, and intralesional methylprednisolone; mercaptopurine, vinblastine, and 500 mg/m 2 metho
- Published
- 2005
50. Langerhans cell histiocytosis: a clinical update
- Author
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Jean Donadieu, Jon Pritchard, and R. Maarten Egeler
- Subjects
Pathology ,medicine.medical_specialty ,Langerhans cell histiocytosis ,business.industry ,Histiocytosis X ,medicine ,Seborrhoeic dermatitis ,Hand–Schüller–Christian disease ,Differential diagnosis ,medicine.disease ,business ,Histiocyte - Published
- 2005
- Full Text
- View/download PDF
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