Bate, J., Baker, S., Breuer, J., Chisholm, J.C., Gray, J., Hambleton, S., Houlton, A., Jit, M., Lowis, S., Makin, G., et al.
(2019). PEPtalk2: results of a pilot randomised controlled trial to compare VZIG and aciclovir as postexposure prophylaxis (PEP) against chickenpox in children with cancer. Archives of disease in childhood,
Vol.104
(1),
pp. 25-29.
show abstract
ObjectiveTo determine the likely rate of patient randomisation and to facilitate sample size calculation for a full-scale phase III trial of varicella zoster immunoglobulin (VZIG) and aciclovir as postexposure prophylaxis against chickenpox in children with cancer.DesignMulticentre pilot randomised controlled trial of VZIG and oral aciclovir.SettingEngland, UK.PatientsChildren under 16 years of age with a diagnosis of cancer: currently or within 6 months of receiving cancer treatment and with negative varicella zoster virus (VZV) serostatus at diagnosis or within the last 3 months.InterventionsStudy participants who have a significant VZV exposure were randomised to receive PEP in the form of VZIG or aciclovir after the exposure.Main outcome measuresNumber of patients registered and randomised within 12 months of the trial opening to recruitment and incidence of breakthrough varicella.ResultsThe study opened in six sites over a 13-month period. 482 patients were screened for eligibility, 32 patients were registered and 3 patients were randomised following VZV exposure. All three were randomised to receive aciclovir and there were no cases of breakthrough varicella.ConclusionsGiven the limited recruitment to the PEPtalk2 pilot, it is unlikely that the necessary sample size would be achievable using this strategy in a full-scale trial. The study identified factors that could be used to modify the design of a definitive trial but other options for defining the best means to protect such children against VZV should be explored.Trial registration numberISRCTN48257441, EudraCT number: 2013-001332-22, sponsor: University of Birmingham..
Vaarwerk, B., Schoot, R.A., Maurice-Stam, H., Slater, O., Hartley, B., Saeed, P., Gajdosova, E., van den Brekel, M.W., Balm, A.J., Hol, M.L., et al.
(2019). Psychosocial well-being of long-term survivors of pediatric head-neck rhabdomyosarcoma. Pediatric blood & cancer,
Vol.66
(2),
pp. e27498-e27498.
Roy Moulik, N., Vaidya, S., Mandeville, H. & Chisholm, J.C.
(2019). Managing peritoneal involvement in children and young people with rhabdomyosarcoma: A single‐center experience from the United Kingdom. Pediatric blood & cancer,
Vol.66
(9).
Vaarwerk, B., Bisogno, G., McHugh, K., Brisse, H.J., Morosi, C., Corradini, N., Jenney, M., Orbach, D., Chisholm, J.C., Ferrari, A., et al.
(2019). Indeterminate Pulmonary Nodules at Diagnosis in Rhabdomyosarcoma: Are They Clinically Significant? A Report From the European Paediatric Soft Tissue Sarcoma Study Group. Journal of clinical oncology,
Vol.37
(9),
pp. 723-730.
Gallego, S., Zanetti, I., Orbach, D., Ranchère, D., Shipley, J., Zin, A., Bergeron, C., de Salvo, G.L., Chisholm, J., Ferrari, A., et al.
(2018). Fusion status in patients with lymph node-positive (N1) alveolar rhabdomyosarcoma is a powerful predictor of prognosis: Experience of the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG). Cancer,
Vol.124
(15),
pp. 3201-3209.
Chisholm, J.C., Suvada, J., Dunkel, I.J., Casanova, M., Zhang, W., Ritchie, N., Choi, Y., Park, J., Das Thakur, M., Simko, S., et al.
(2018). BRIM-P: A phase I, open-label, multicenter, dose-escalation study of vemurafenib in pediatric patients with surgically incurable, BRAF
mutation-positive melanoma. Pediatric blood & cancer,
Vol.65
(5),
pp. e26947-e26947.
Bisogno, G., Jenney, M., Bergeron, C., Gallego Melcón, S., Ferrari, A., Oberlin, O., Carli, M., Stevens, M., Kelsey, A., De Paoli, A., et al.
(2018). Addition of dose-intensified doxorubicin to standard chemotherapy for rhabdomyosarcoma (EpSSG RMS 2005): a multicentre, open-label, randomised controlled, phase 3 trial. The lancet oncology,
Vol.19
(8),
pp. 1061-1071.
Moreno, L., Casanova, M., Chisholm, J.C., Berlanga, P., Chastagner, P.B., Baruchel, S., Amoroso, L., Gallego Melcón, S., Gerber, N.U., Bisogno, G., et al.
(2018). Phase I results of a phase I/II study of weekly nab-paclitaxel in paediatric patients with recurrent/refractory solid tumours: A collaboration with innovative therapies for children with cancer. European journal of cancer,
Vol.100,
pp. 27-34.
Ali, A., Mohamed, M., Chisholm, J. & Thway, K.
(2017). Solid-Pattern Desmoplastic Small Round Cell Tumor. International journal of surgical pathology,
Vol.25
(2),
pp. 158-161.
Ferrari, A., Trama, A., De Paoli, A., Bergeron, C., Merks, J.H., Jenney, M., Orbach, D., Chisholm, J.C., Gallego, S., Glosli, H., et al.
(2017). Access to clinical trials for adolescents with soft tissue sarcomas: Enrollment in European pediatric Soft tissue sarcoma Study Group (EpSSG) protocols. Pediatric blood & cancer,
Vol.64
(6).
Selfe, J., Olmos, D., Al-Saadi, R., Thway, K., Chisholm, J., Kelsey, A. & Shipley, J.
(2017). Impact of fusion gene status versus histology on risk-stratification for rhabdomyosarcoma: Retrospective analyses of patients on UK trials. Pediatric blood & cancer,
Vol.64
(7),
pp. e26386-e26386.
Chisholm, J.C., Merks, J.H., Casanova, M., Bisogno, G., Orbach, D., Gentet, J.-., Thomassin-Defachelles, A.-., Chastagner, P., Lowis, S., Ronghe, M., et al.
(2017). Open-label, multicentre, randomised, phase II study of the EpSSG and the ITCC evaluating the addition of bevacizumab to chemotherapy in childhood and adolescent patients with metastatic soft tissue sarcoma (the BERNIE study). European journal of cancer,
Vol.83,
pp. 177-184.
Kieran, M.W., Chisholm, J., Casanova, M., Brandes, A.A., Aerts, I., Bouffet, E., Bailey, S., Leary, S., MacDonald, T.J., Mechinaud, F., et al.
(2017). Phase I study of oral sonidegib (LDE225) in pediatric brain and solid tumors and a phase II study in children and adults with relapsed medulloblastoma. Neuro-oncology,
Vol.19
(11),
pp. 1542-1552.
Clement, S.C., Schoot, R.A., Slater, O., Chisholm, J.C., Abela, C., Balm, A.J., van den Brekel, M.W., Breunis, W.B., Chang, Y.C., Davila Fajardo, R., et al.
(2016). Endocrine disorders among long-term survivors of childhood head and neck rhabdomyosarcoma. European journal of cancer,
Vol.54,
pp. 1-10.
Phillips, R.S., Sung, L., Amman, R.A., Riley, R.D., Castagnola, E., Haeusler, G.M., Klaassen, R., Tissing, W.J., Lehrnbecher, T., Chisholm, J., et al.
(2016). Predicting microbiologically defined infection in febrile neutropenic episodes in children: global individual participant data multivariable meta-analysis. British journal of cancer,
Vol.114
(6),
pp. 623-630.
Veal, G.J., Errington, J., Sastry, J., Chisholm, J., Brock, P., Morgenstern, D., Pritchard-Jones, K. & Chowdhury, T.
(2016). Adaptive dosing of anticancer drugs in neonates: facilitating evidence-based dosing regimens. Cancer chemotherapy and pharmacology,
Vol.77
(4),
pp. 685-692.
Herd, F., Bate, J., Chisholm, J., Johnson, E. & Phillips, B.
(2016). Variation in practice remains in the UK management of paediatric febrile neutropenia: Table 1. Archives of disease in childhood,
Vol.101
(4),
pp. 410-411.
Carceller, F., Bautista, F.J., Fowkes, L.A., Marshall, L.V., Sirvent, S.I., Chisholm, J.C., Pearson, A.D., Koh, D.-. & Moreno, L.
(2016). Response Assessment in Paediatric Phase I Trials According to RECIST Guidelines: Survival Outcomes, Patterns of Progression and Relevance of Changes in Tumour Measurements. Pediatric blood & cancer,
Vol.63
(8),
pp. 1400-1406.
Thway, K., Chisholm, J., Hayes, A., Swansbury, J. & Fisher, C.
(2015). Pediatric low-grade fibromyxoid sarcoma mimicking ossifying fibromyxoid tumor: adding to the diagnostic spectrum of soft tissue tumors with a bony shell. Hum pathol,
Vol.46
(3),
pp. 461-466.
show abstract
We describe a case of superficial low-grade fibromyxoid sarcoma (LGFMS) in a 12-year-old boy, confirmed by the detection of FUS-CREB3L2 fusion transcripts by reverse-transcription polymerase chain reaction and FUS rearrangement with fluorescence in situ hybridization, which had morphological features similar to ossifying fibromyxoid tumor (OFMT), including an almost complete rim of mature, metaplastic bone. LGFMS and OFMT can appear morphologically similar, with bland ovoid cells within a fibrous to myxoid matrix. Both can occur superficially; and whereas MUC4 immunoreactivity is characteristic of LGFMS, this can also be seen in some OFMTs. As the morphological spectrum of LGFMS is wide, we highlight the potential for diagnostic confusion with OFMT, which is clinically pertinent as most OFMTs behave in a benign manner whereas LGFMS is a malignant neoplasm with a propensity for local recurrence and a significant metastatic rate. .
Schoot, R.A., Slater, O., Ronckers, C.M., Zwinderman, A.H., Balm, A.J., Hartley, B., van den Brekel, M.W., Gupta, S., Saeed, P., Gajdosova, E., et al.
(2015). Adverse events of local treatment in long-term head and neck rhabdomyosarcoma survivors after external beam radiotherapy or AMORE treatment. European journal of cancer,
Vol.51
(11),
pp. 1424-1434.
Norman, G., Fayter, D., Lewis-Light, K., Chisholm, J., McHugh, K., Levine, D., Jenney, M., Mandeville, H., Gatz, S. & Phillips, B., et al.
(2015). An emerging evidence base for PET-CT in the management of childhood rhabdomyosarcoma: systematic review. Bmj open,
Vol.5
(1),
p. e006030.
show abstract
INTRODUCTION: Rhabdomyosarcoma (RMS) management depends on risk stratification at diagnosis and treatment response. Assessment methods include CT, MRI, bone scintigraphy, histological analysis and bone marrow biopsy. Advanced functional imaging (FI) has potential to improve staging accuracy and management strategies. METHODS AND ANALYSIS: We conducted a systematic review (PROSPERO 2013:CRD42013006128) of diagnostic accuracy and clinical effectiveness of FI in histologically proven paediatric RMS. PRISMA guidance was followed. We searched 10 databases to November 2013. Studies with ≥10 patients with RMS which compared positron emission tomography (PET), PET-CT or diffusion-weighted imaging (DWI) MRI to conventional imaging at any treatment stage were included. Study quality was assessed. Limited, heterogeneous effectiveness data required narrative synthesis, illustrated by plotting sensitivity and specificity in receiver operating curve (ROC) space. RESULTS: Eight studies (six PET-CT, two PET) with 272 RMS patients in total were included. No DWI-MRI studies met inclusion criteria. Pooled estimates were not calculated due to sparseness of data. Limited evidence indicated initial PET-CT results were predictive of survival. PET-CT changed management of 7/40 patients. Nodal involvement PET-CT: sensitivity ranged from 80% to 100%; specificity from 89% to 100%. Distant metastatic involvement: PET-CT sensitivity ranged from 95% to 100%; specificity from 80% to100%. Data on metastases in different sites were sparse. Limited data were found on outcome prediction by PET-CT response. DISSEMINATION AND ETHICS: PET/PET-CT may increase initial staging accuracy in paediatric RMS, specifically in the detection of nodal involvement and distant metastatic spread. There is a need to further assess PET-CT for this population, ideally in a representative, unbiased and transparently selected cohort of patients..
Gatz, S.A., Thway, K., Mandeville, H., Kerawala, C., MacVicar, D. & Chisholm, J.
(2015). Chemotherapy responsiveness in a patient with multiply relapsed ameloblastic fibro-odontosarcoma of the maxilla. Pediatric blood & cancer,
Vol.62
(11),
pp. 2029-2032.
Lehrnbecher, T., Aplenc, R., Rivas Pereira, F., Lassaletta, A., Caselli, D., Kowalczyk, J., Chisholm, J., Sung, L. & Grp, S.I.
(2014). Variations in non-pharmacological anti-infective measures in childhood leukemia - results of an international survey (vol 97, pg 1548, 2012). Haematologica,
Vol.99
(7),
pp. 1272-1272.
Morgenstern, D.A., Hargrave, D., Marshall, L.V., Gatz, S.A., Barone, G., Crowe, T., Pritchard-Jones, K., Zacharoulis, S., Lancaster, D.L., Vaidya, S.J., et al.
(2014). Toxicity and outcome of children and adolescents participating in phase I/II trials of novel anticancer drugs: the Royal Marsden experience. J pediatr hematol oncol,
Vol.36
(3),
pp. 218-223.
show abstract
Early phase trials are crucial in developing new therapies for poor prognosis childhood malignancies. Outcomes and toxicities of children treated on phase I/II trials at the Royal Marsden, one of the largest pediatric oncology early phase trial units in Europe, were examined to provide a baseline dataset and generate hypotheses. All patients recruited over a 10-year period to December 2011 were included. Variables including baseline characteristics, time on study, survival, toxicities, and admissions were collected. Seventy-two patients were recruited to 21 trials (5 phase I, 16 phase II; overall 12 involved molecularly targeted agents). Median age at consent was 12.4 years. Dose-limiting toxicities were rare in phase I trial participants (2 of 15 evaluable patients, 13%); the most common reason for leaving trials was disease progression (76%), rather than drug toxicity (1.7%). Median time on trial was 1.3 months (phase I patients) and 3.3 months (phase II). Early phase trials in children are safe and unexpected toxic side effects are infrequent. Patients and their families are willing to travel to access novel therapies, although the overall prognosis for these individuals is poor. Continued expansion of the portfolio is needed ultimately to improve the outcomes for those with resistant disease. .
Calton, E.A., Le Doare, K., Appleby, G., Chisholm, J.C., Sharland, M., Ladhani, S.N. & Participants, C.A.
(2014). Invasive Bacterial and Fungal Infections in Paediatric Patients with Cancer: Incidence, Risk Factors, Aetiology and Outcomes in aUK Regional Cohort 2009-2011. Pediatric blood & cancer,
Vol.61
(7),
pp. 1239-1245.
Norman, G., Fayter, D., Light-Lewis, K., Chisholm, J., Mandeville, H., Gatz, S., Levine, D., Jenney, M., McHugh, K. & Phillips, B., et al.
(2014). THE ROLE OF PET-CT IN THE MANAGEMENT OF CHILDHOOD RHABDOMYOSARCOMA: SYSTEMATIC REVIEW. Pediatric blood & cancer,
Vol.61,
pp. S133-S133.
Schoot, R.A., Slater, O., Ronckers, C.M., Zwinderman, A.H., Balm, A.J., Hartley, B., van de Brekel, M., Gupta, S., Saeed, P., Gajdosova, E., et al.
(2014). ADVERSE EVENTS OF LOCAL TREATMENT IN HEAD AND NECK RHABDOMYOSARCOMA SURVIVORS AFTER EXTERNAL BEAM RADIOTHERAPY OR AMORE TREATMENT. Pediatric blood & cancer,
Vol.61,
pp. S311-S311.
Bisogno, G., De Salvo, G.L., Bergeron, C., Carli, M., Ferrari, A., Jenney, M., Mercks, H., Kelsey, A., Gallego, S., Chisholm, J., et al.
(2014). THE ROLE OF DOXORUBICIN IN THE TREATMENT OF RHABDOMYOSARCOMA: PRELIMINARY RESULTS FROM THE EPSSG RMS2005 RANDOMIZED TRIAL. Pediatric blood & cancer,
Vol.61,
pp. S133-S134.
Dommett, R., Chisholm, J., Turner, M., Bajaj-Elliott, M. & Klein, N.J.
(2013). Mannose-binding lectin genotype influences frequency and duration of infectious complications in children with malignancy. J pediatr hematol oncol,
Vol.35
(1),
pp. 69-75.
show abstract
Children with cancer receiving identical treatment differ in their experience of infection, suggesting that variations in immunity may influence susceptibility to infection. Studies of the influence of mannose-binding lectin (MBL), an important component of the innate immune system, in children with febrile neutropenia (FN) have yielded conflicting results. We examined the role of MBL in infection susceptibility in the largest cohort of children with cancer reported to date. MBL levels were measured and genotyping performed on children (≤16 y) receiving chemotherapy for cancer in London, UK. Clinical data from FN episodes were recorded prospectively. MBL status was assessed in 269 children; 513 episodes of FN were captured from 211 patients. Patients with MBL2 polymorphisms experienced more FN episodes than wildtype genotype (median 2 vs. 1, respectively; P = 0.074) and more episodes with documented infection (P = 0.045). Patients experiencing multiple FN episodes had lower MBL levels (P = 0.036). MBL genotype influenced duration of episode in some groups: high-risk MBL-deficient patients spent up to 5 nights longer/episode in hospital than equivalent wildtypes. These results indicate that MBL deficiency influences both susceptibility to and outcome of FN episodes and may be most important in those patients at higher risk of complications of FN..
Bate, J., Gibson, F., Johnson, E., Selwood, K., Skinner, R. & Chisholm, J.
(2013). Neutropenic sepsis: prevention and management of neutropenic sepsis in cancer patients (NICE Clinical Guideline CG151). Archives of disease in childhood-education and practice edition,
Vol.98
(2),
pp. 73-75.
Bate, J., Gibson, F., Selwood, K., Skinner, R., Phillips, B. & Chisholm, J.C.
(2013). A reaudit of current febrile neutropenia practice in UK paediatric oncology centres prior to implementation of NICE guidance. Archives of disease in childhood,
Vol.98
(4),
pp. 315-316.
Gibson, F., Chisholm, J., Blandford, E., Donachie, P., Hartley, J., Lane, S., Selwood, K., Skinner, R., Phillips, R. & CCLG Supportive Care Group, , et al.
(2013). Developing a national 'low risk' febrile neutropenia framework for use in children and young people's cancer care. Support care cancer,
Vol.21
(5),
pp. 1241-1251.
show abstract
PURPOSE: A Delphi study was undertaken to develop a framework guidance that would rationalise and standardise the care of children with febrile neutropenia (FNP) across the UK. METHODS: A mailed Delphi survey was undertaken with health professionals working in children's cancer units. The survey employed two rounds of feedback on 22 practice statements drawn from a systematic review of clinical evidence. Consensus was assumed for any statement where 80+ % of respondents indicated that they "agreed" or "strongly agreed". RESULTS: Consensus was reached on 21 of the 22 practice statements in round 1 that were categorised into six areas: definition of fever and neutropenia, initial management and choice of antibiotic, defining low-risk patients, strategy in low-risk patients and alternative approaches. Consensus could not be reached on whether patients needed to be afebrile to be suitable for discharge and the required length of outpatient antibiotic treatment. CONCLUSIONS: A Delphi survey allowed the successful development of a national framework for identification and management of children with FNP. The use of an existing well-functioning professional network was key in this project's success..
Orbach, D., Mosseri, V., Stevens, M., Rey, A., Gallelo, S., Kelsey, A., Christine, D., Brenann, B., Van Noesel, M., Gaze, M., et al.
(2013). NON PARAMENINGEAL HEAD-AND-NECK RHABDOMYOSARCOMA IN CHILDREN AND ADOLESCENT: A VERY LONG TERM EXPERIENCE OF THE INTERNATIONAL SOCIETY OF PEDIATRIC ONCOLOGY MALIGNANT MESENCHYMAL TUMOR (SIOP-MMT) COMMITTEE. Pediatric blood & cancer,
Vol.60,
pp. 36-36.
Rousseau, R., Geoerger, B., Chisholm, J., Casanova, M., Merks, J., Monnet, A., Dhalluin, C. & Oberlin, O.
(2013). THE BERNIE STUDY: A PHASE II STUDY EVALUATING ADDITION OF BEVACIZUMAB TO CHEMOTHERAPY IN CHILDREN AND ADOLESCENTS WITH METASTATIC RHABDOMYOSARCOMA AND NON-RHABDOMYOSARCOMA SOFT TISSUE SARCOMA. Pediatric blood & cancer,
Vol.60,
pp. 92-92.
Schoot, R.A., McHugh, K., van Rijn, R.R., Kremer, L.C., Chisholm, J.C., Caron, H.N. & Merks, J.H.
(2013). Response assessment in pediatric rhabdomyosarcoma: can response evaluation criteria in solid tumors replace three-dimensional volume assessments?. Radiology,
Vol.269
(3),
pp. 870-878.
show abstract
PURPOSE: To investigate (a) interobserver variability for three-dimensional (3D) (based on European Pediatric Soft-Tissue Sarcoma Study Group [EpSSG] guidelines) and one-dimensional (1D) (based on Response Evaluation Criteria in Solid Tumors [RECIST]) response assessments, (b) intermethod variability between EpSSG guidelines and RECIST, and (c) clinically relevant consequences of interobserver and intermethod variability in pediatric patients with rhabdomyosarcoma. MATERIALS AND METHODS: The study was approved by the Academic Medical Center Ethics Committee and the Great Ormond Street Hospital Ethics Committee; both committees waived the requirement for informed consent because of the retrospective nature of the study. Data were analyzed from 124 consecutive male and female children and young adults (age range, 1-18 years) with rhabdomyosarcoma at two institutions (1999-2009) with relevant imaging studies. Tumors were measured by two radiologists (1D and 3D measurements) at diagnosis and after induction chemotherapy. Interobserver variability was analyzed by using three different tests, and the intermethod variation was calculated. RESULTS: Sixty-four eligible patients were included (median age, 4.6 years). Agreement between observers for EpSSG guidelines and RECIST was moderate (κ = 0.565 and 0.592, respectively); interobserver variation led to different potential treatment decisions in nine (14%) and 11 (17%) of the 64 patients, respectively. Comparison of EpSSG guidelines and RECIST resulted in 13 discrepant response classifications (20%), which were equally distributed (under- and overestimation of response) and led to consequences for treatment choice in five patients (8%). CONCLUSION: EpSSG guidelines and RECIST are not interchangeable; neither technique demonstrated superiority in this study. These findings should be taken into account in future study protocol design. Online supplemental material is available for this article..
Williamson, D., Missiaglia, E., Chisholm, J. & Shipley, J.
(2012). Inconvenience of convenience cohorts--letter. Cancer epidemiol biomarkers prev,
Vol.21
(8),
p. 1388.
Bate, J., Chisholm, J., Skinner, R., Breuer, J., Ramsay, M., Wheatley, K., Hambleton, S. & Heath, P.T.
(2012). Varicella post-exposure prophylaxis in children with cancer: urgent need for a randomised controlled trial. Archives of disease in childhood,
Vol.97
(9),
pp. 853-854.
Chisholm, J., Phillips, P., Sutton, A., Riley, R., Picton, S. & Stewart, L.
(2012). Predicting Infectious Complications in Neutropenic Children and young people with Cancer Optimizing risk predictive strategies in febrile neutropenic episodes in children and young people undergoing treatment for malignant disease. Systematic reviews in pharmacy,
.
Missiaglia, E., Williamson, D., Chisholm, J., Wirapati, P., Pierron, G., Petel, F., Concordet, J.-., Thway, K., Oberlin, O., Pritchard-Jones, K., et al.
(2012). PAX3/FOXO1 fusion gene status is the key prognostic molecular marker in rhabdomyosarcoma and significantly improves current risk stratification. J clin oncol,
Vol.30
(14),
pp. 1670-1677.
show abstract
PURPOSE: To improve the risk stratification of patients with rhabdomyosarcoma (RMS) through the use of clinical and molecular biologic data. PATIENTS AND METHODS: Two independent data sets of gene-expression profiling for 124 and 101 patients with RMS were used to derive prognostic gene signatures by using a meta-analysis. These and a previously published metagene signature were evaluated by using cross validation analyses. A combined clinical and molecular risk-stratification scheme that incorporated the PAX3/FOXO1 fusion gene status was derived from 287 patients with RMS and evaluated. RESULTS: We showed that our prognostic gene-expression signature and the one previously published performed well with reproducible and significant effects. However, their effect was reduced when cross validated or tested in independent data and did not add new prognostic information over the fusion gene status, which is simpler to assay. Among nonmetastatic patients, patients who were PAX3/FOXO1 positive had a significantly poorer outcome compared with both alveolar-negative and PAX7/FOXO1-positive patients. Furthermore, a new clinicomolecular risk score that incorporated fusion gene status (negative and PAX3/FOXO1 and PAX7/FOXO1 positive), Intergroup Rhabdomyosarcoma Study TNM stage, and age showed a significant increase in performance over the current risk-stratification scheme. CONCLUSION: Gene signatures can improve current stratification of patients with RMS but will require complex assays to be developed and extensive validation before clinical application. A significant majority of their prognostic value was encapsulated by the fusion gene status. A continuous risk score derived from the combination of clinical parameters with the presence or absence of PAX3/FOXO1 represents a robust approach to improving current risk-adapted therapy for RMS..
George, S.L., Broster, S., Chisholm, J.C. & Brock, P.
(2012). Docetaxel in the treatment of children with refractory or relapsed hepatoblastoma. J pediatr hematol oncol,
Vol.34
(7),
pp. e295-e297.
show abstract
We report on the use of single-agent docetaxel (100 mg/m(2) in children >10 kg, 3.3 mg/kg in children <10 kg), given as a 1-hour infusion at 21-day intervals in 5 children with relapsed or refractory hepatoblastoma. One patient achieved complete remission of pulmonary metastases after 2 courses of docetaxel and remains well 10 years later, after completion of 13 courses of docetaxel and whole-lung radiotherapy. One patient showed a partial response to docetaxel based on α-fetoprotein measurements. Docetaxel shows some activity in progressive hepatoblastoma in this small case series and is a potential drug for future study in this disease..
Lehrnbecher, T., Aplenc, R., Rivas Pereira, F., Lassaletta, A., Caselli, D., Kowalczyk, J., Chisholm, J., Sung, L. & Grp, S.I.
(2012). Variations in non-pharmacological anti-infective measures in childhood leukemia - results of an international survey. Haematologica-the hematology journal,
Vol.97
(10),
pp. 1548-1552.
Missiaglia, E., Williamson, D., Chisholm, J., Wirapati, P., Pierron, G., Petel, F., Concordet, J.-., Thway, K., Oberlin, O., Pritchard-Jones, K., et al.
(2012). Questionable Universal Validity of PAX3/FOXO1 Fusion Gene Status As Molecular Marker for Improvement of Risk Stratification in Rhabdomyosarcoma Therapy Reply. Journal of clinical oncology,
Vol.30
(32),
pp. 4040-4041.
Geoerger, B., Aerts, I., Casanova, M., Chisholm, J., Hargrave, D., Leary, S.E., Ashley, D., Bouffet, E., MacDonald, T., Di Giannatale, A., et al.
(2012). UPDATED RESULTS FROM A PHASE I STUDY OF LDE225, A SMOOTHENED ANTAGONIST, IN PEDIATRIC PATIENTS WITH RECURRENT MEDULLOBLASTOMA OR OTHER SOLID TUMORS. Pediatric blood & cancer,
Vol.59
(6),
pp. 980-980.
Patel, S.R., Bate, J., Mathews, R., Chisholm, J. & Heath, P.T.
(2012). VACCINATION STATUS OF CHILDREN WITH CANCER AFTER COMPLETION OF STANDARD-DOSE CHEMOTHERAPY AND AFTER HAEMATOPOIETIC STEM CELL TRANSPLANT. Pediatric blood & cancer,
Vol.59
(6),
pp. 1116-1116.
Morgenstern, D., Hargrave, D., Marshall, L.V., Gatz, S.A., Barone, G., Crowe, T., Pritchard-Jones, K., Zacharoulis, S., Lancaster, D.L., Vaidya, S.J., et al.
(2012). EARLY PHASE CLINICAL TRIALS IN PAEDIATRIC ONCOLOGY THE ROYAL MARSDEN EXPERIENCE. Pediatric blood & cancer,
Vol.59
(6),
pp. 1091-1091.
Geoerger, B., Chisholm, J., Le Deley, M.-., Gentet, J.-., Zwaan, C.M., Dias, N., Jaspan, T., Mc Hugh, K., Couanet, D., Hain, S., et al.
(2011). Phase II study of gemcitabine combined with oxaliplatin in relapsed or refractory paediatric solid malignancies: An innovative therapy for children with Cancer European Consortium Study. Eur j cancer,
Vol.47
(2),
pp. 230-238.
show abstract
AIM: To assess objective response rates after 4 cycles of gemcitabine in combination with oxaliplatin in children and adolescents with relapsed or refractory solid tumours. METHODS: This multicentre, non-randomised Phase II study included five strata: neuroblastoma, osteosarcoma, medulloblastoma and other CNS tumours strata with two-stage Simon designs and a miscellaneous, extra-cranial solid tumour stratum with descriptive design. Eligibility criteria included: age 6 months to 21 years; measurable, relapsed or refractory solid malignancy; no more than one previous salvage therapy. Gemcitabine was administered intravenously at 1000 mg/m(2) over 100 min followed by oxaliplatin at 100mg/m(2) over 120 min on Day 1 of a 14-d cycle. Tumour response was assessed every 4 cycles according to WHO criteria. RESULTS: Ninety-three out of 95 patients enrolled in 25 centres received treatment: 12 neuroblastoma; 12 osteosarcoma; 14 medulloblastoma; 13 other CNS tumours and 42 miscellaneous non-CNS solid tumours. Median age was 11.7 years (range, 1.3-20.8 years). Tumour control (CR+PR+SD) at 4 cycles was obtained in 30/93 evaluable patients (32.3%; 95% confidence interval (CI), 22.9-42.7%), including four PR: 1/12 patients with osteosarcoma, 1/12 with medulloblastoma, 1/12 with rhabdomyosarcoma and 1/4 with other sarcoma. Five out of 12 eligible patients with neuroblastoma experienced stable disease. During a total of 481 treatment cycles (median 4, range 1-24 per patient), the most common treatment-related toxicities were haematologic (leukopenia, neutropenia, thrombocytopenia) and neurological (dysesthesia, paresthesia). CONCLUDING STATEMENT: The gemcitabine-oxaliplatin combination administered in a bi-weekly schedule has acceptable safety profile with limited activity in children with relapsed or refractory solid tumours..
Chisholm, J.C., Marandet, J., Rey, A., Scopinaro, M., de Toledo, J.S., Merks, J.H., O'Meara, A., Stevens, M.C. & Oberlin, O.
(2011). Prognostic factors after relapse in nonmetastatic rhabdomyosarcoma: a nomogram to better define patients who can be salvaged with further therapy. J clin oncol,
Vol.29
(10),
pp. 1319-1325.
show abstract
PURPOSE: Previous studies suggest poor outcome in children with relapsed rhabdomyosarcoma (RMS). A better understanding is needed of which patients can be salvaged after first relapse. PATIENTS AND METHODS: The analysis included children with nonmetastatic RMS and embryonal sarcoma enrolled onto the International Society of Paediatric Oncology (SIOP) Malignant Mesenchymal Tumor (MMT) 84, 89, and 95 studies who relapsed after achieving complete local control with primary therapy. All patients included in the analysis had follow-up for ≥ 3.0 years after the last event. The clinical features, initial treatment characteristics, and features of the relapse were correlated with survival in univariate and multivariate analyses. RESULTS: In all, 474 eligible patients were identified for the study. At ≥ 3.0 years from the last event, 176 (37%) were alive ("cured"). In a full-model multivariate analysis, the factors identified at first relapse that most strongly associated with poor outcome were metastatic relapse (odds ratio [OR], 4.19; 95% CI, 2.0 to 8.5), prior radiotherapy treatment (OR, 3.64; 95% CI, 2.1 to 6.4), initial tumor size > 5 cm (OR, 2.53; 95% CI, 1.5 to 4.1), and time of relapse < 18 months from diagnosis (OR, 2.20; 95% CI, 1.3 to 3.6). Unfavorable primary disease site, nodal involvement at diagnosis, alveolar histology, and previous three- or six-drug chemotherapy were also independently associated with poor outcome. To estimate chance of cure for individual patients, a nomogram was developed, which allowed for weighting of these significant factors. CONCLUSION: Some children with relapsed RMS remain curable. It is now possible to estimate the chance of salvage for individual children to direct therapy appropriately toward cure, use of experimental therapies, and/or palliation..
Slade, I., Bacchelli, C., Davies, H., Murray, A., Abbaszadeh, F., Hanks, S., Barfoot, R., Burke, A., Chisholm, J., Hewitt, M., et al.
(2011). DICER1 syndrome: clarifying the diagnosis, clinical features and management implications of a pleiotropic tumour predisposition syndrome. J med genet,
Vol.48
(4),
pp. 273-278.
show abstract
BACKGROUND: Constitutional DICER1 mutations were recently reported to cause familial pleuropulmonary blastoma (PPB). AIM: To investigate the contribution and phenotypic spectrum of constitutional and somatic DICER1 mutations to cancer. METHODS AND RESULTS: The authors sequenced DICER1 in constitutional DNA from 823 unrelated patients with a variety of tumours and in 781 cancer cell lines. Constitutional DICER1 mutations were identified in 19 families including 11/14 with PPB, 2/3 with cystic nephroma, 4/7 with ovarian Sertoli-Leydig-type tumours, 1/243 with Wilms tumour (this patient also had a Sertoli-Leydig tumour), 1/1 with intraocular medulloepithelioma (this patient also had PPB), 1/86 with medulloblastoma/infratentorial primitive neuroectodermal tumour, and 1/172 with germ cell tumour. The inheritance was investigated in 17 families. DICER1 mutations were identified in 25 relatives: 17 were unaffected, one mother had ovarian Sertoli-Leydig tumour, one half-sibling had cystic nephroma, and six relatives had non-toxic thyroid cysts/goitre. Analysis of eight tumours from DICER1 mutation-positive patients showed universal retention of the wild-type allele. DICER1 truncating mutations were identified in 4/781 cancer cell lines; all were in microsatellite unstable lines and therefore unlikely to be driver mutations. CONCLUSION: Constitutional DICER1 haploinsufficiency predisposes to a broad range of tumours, making a substantial contribution to PPB, cystic nephroma and ovarian Sertoli-Leydig tumours, but a smaller contribution to other tumours. Most mutation carriers are unaffected, indicating that tumour risk is modest. The authors define the clinical contexts in which DICER1 mutation testing should be considered, the associated tumour risks, and the implications for at-risk individuals. They have termed this condition 'DICER1 syndrome'. ACCESSION NUMBERS: The cDNA Genbank accession number for the DICER1 sequence reported in this paper is NM_030621.2..
Bate, J., Chisholm, J., Heath, P.T., Breuer, J., Skinner, R., Manley, S., Patel, S., Wheatley, K., Ramsay, M., Kearns, P.R., et al.
(2011). PEPtalk: postexposure prophylaxis against varicella in children with cancer. Archives of disease in childhood,
Vol.96
(9),
pp. 841-845.
Lehrnbecher, T., Aplenc, R., Pereira, F.R., Lassaletta, A., Caselli, D., Kowalczyk, J., Chisholm, J. & Sung, L.
(2011). INSTITUTIONAL VARIATIONS IN NON-PHARMACOLOGICAL ANTI-INFECTIVE MEASURES - RESULTS OF AN INTERNATIONAL SURVEY. Pediatric blood & cancer,
Vol.57
(5),
pp. 847-847.
Bate, J., Patel, S.R., Chisholm, J., Heath, P.T. & CCLG,
(2010). Immunisation Practices of Paediatric Oncology and Shared Care Oncology Consultants: A United Kingdom Survey. Pediatric blood & cancer,
Vol.54
(7),
pp. 941-946.
Jorgensen, M., Bate, J., Gatscher, S. & Chisholm, J.C.
(2010). Invasive pneumococcal disease following treatment for choroid plexus carcinoma. Support care cancer,
Vol.18
(5),
pp. 647-650.
show abstract
INTRODUCTION: A 13-month-old child was treated for choroid plexus carcinoma with partial embolisation, complete surgical excision and chemotherapy. The patient's course was complicated by the presence of chronic bilateral subdural collections. CASE REPORT: Four months from completing treatment, the child presented with an empyema in the subdural space caused by Streptococcus pneumoniae subtype 6A. DISCUSSION: The case highlights a number of questions about pneumococcal immunisation after standard chemotherapy. Evidence-based guidelines are required urgently to direct best practice..
Rees, H., Andrews, M., Broster, S., Nicholson, J., Skinner, R., Chisholm, J. & Canc, S.C.
(2010). Influenza vaccination during cancer therapy. Archives of disease in childhood,
Vol.95
(7).
Chisholm, J., Marandet, J., Rey, A. & Oberlin, O.
(2010). PROGNOSTIC FACTORS AFTER RELAPSE IN NON-METASTATIC RHABDOMYOSARCOMA: WHO CAN BE SALVAGED?. Pediatric blood & cancer,
Vol.55
(5),
pp. 836-836.
Schoot, R., McHugh, K., van Rijn, R., Chisholm, J. & Merks, J.
(2010). ARE THE RECIST CRITERIA USEFUL IN ASSESSING RESPONSE IN PAEDIATRIC RHABDOMYOSARCOMA?. Pediatric blood & cancer,
Vol.55
(5),
pp. 901-902.
Chisholm, J.C., Casanova, M., Geoerger, B., Merks, J.H., Massimini, G., Moore, N., Rooney, I.A., Viviers, L. & Oberlin, O.
(2010). A phase II study evaluating addition of bevacizumab to chemotherapy in childhood and adolescent patients presenting with metastatic rhabdomyosarcoma (RMS) and non-rhabdomyosarcoma soft tissue sarcoma (NRSTS). Journal of clinical oncology,
Vol.28
(15).
Gibson, F., Hartley, J., Lane, S., Phillips, R., Selwood, K., Skinner, R. & Chisholm, J.
(2009). Reaching A National Consensus On An Approach To Low Risk Febrile Neutropenia: The Challenges of A Delphi Survey. European journal of oncology nursing,
Vol.13
(1),
pp. 63-63.
Thomas, L., Baggen, L., Chisholm, J. & Sharland, M.
(2009). Diagnosis and treatment of aspergillosis in children. Expert review of anti-infective therapy,
Vol.7
(4),
pp. 461-472.
Bate, J., Ladhani, S., Sharland, M., Chisholm, J., Lamagni, T., Ramsay, M., Johnson, A. & Pebody, R.
(2009). Infection-Related Mortality in Children With Malignancy in England and Wales, 2003-2005. Pediatric blood & cancer,
Vol.53
(3),
pp. 371-374.
Dommett, R., Geary, J., Freeman, S., Hartley, J., Sharland, M., Davidson, A., Tulloh, R., Taj, M., Stoneham, S. & Chisholm, J.C., et al.
(2009). Successful introduction and audit of a step-down oral antibiotic strategy for low risk paediatric febrile neutropaenia in a UK, multicentre, shared care setting. European journal of cancer,
Vol.45
(16),
pp. 2843-2849.
Patel, S.R., Chisholm, J.C. & Heath, P.T.
(2008). Vaccinations in children treated with standard-dose cancer therapy or hematopoietic stem cell transplantation. Pediatric clinics of north america,
Vol.55
(1),
pp. 169-+.
Laddie, J. & Chisholm, J.
(2007). A survey of parent and staff views on management by risk stratification in children with febrile neutropenia (FN). Pediatric blood & cancer,
Vol.49
(4),
pp. 508-509.
Phillips, R., Skinner, R. & Chisholm, J.C.
(2007). Treating low-risk febrile neutropenia: Jenny's story. Archives of disease in childhood,
Vol.92
(1),
pp. 7-8.
Andrews, M., Chisholm, J., Nicholson, J., Broster, S. & Rees, H.
(2007). Cross-sectional survey of influenza vaccination uptake in children with cancer. Pediatric blood & cancer,
Vol.49
(4),
pp. 509-509.
Chisholm, J.C.
(2007). Reimmunization after therapy for childhood cancer. Clinical infectious diseases,
Vol.44
(5),
pp. 643-645.
Phillips, B., Selwood, K., Lane, S.M., Skinner, R., Gibson, F. & Chisholm, J.C.
(2007). Variation in policies for the management of febrile neutropenia in United Kingdom Children's Cancer Study Group centres. Archives of disease in childhood,
Vol.92
(6),
pp. 495-498.
Chisholm, J.C., Machin, D., McDowell, H., McHugh, K., Ellershaw, C., Jenney, M., Foot, A.B. & Children's Cancer and Leukaemia Group (CCLG; formerly United Kingdom Children's Cancer Study Group),
(2007). Efficacy of carboplatin given in a phase II window study to children and adolescents with newly diagnosed metastatic soft tissue sarcoma. Eur j cancer,
Vol.43
(17),
pp. 2537-2544.
show abstract
AIM: The activity of carboplatin was evaluated in a phase II window study in previously untreated children with metastatic soft tissue sarcoma. METHODS: Children with poor-risk metastatic disease (over 10 years and/or with bone/bone marrow involvement) treated in the SIOP MMT 98 study were scheduled to receive two courses of intravenous carboplatin (area under curve [AUC] of 10), 21 days apart. RESULTS: Sixteen eligible patients were entered into the rhabdomyosarcoma (RMS) group. Response (complete remission or partial remission) was seen in five children (31%, 95% confidence interval (CI) 14-56%). Ten eligible patients with other soft tissue sarcomas were recruited into the non-RMS group. Two responses (20%, 95% CI 6-51%) were seen. Toxicity in both groups was predictable nausea, vomiting and marrow suppression and there were no toxic deaths. CONCLUSION: Single-agent carboplatin at AUC of 10 has an acceptable toxicity profile but only moderate efficacy in poor-risk metastatic soft tissue sarcoma..
Duncan, C., Chisholm, J.C., Freeman, S., Riley, U., Sharland, M. & Pritchard-Jones, K.
(2007). A prospective study of admissions for febrile neutropenia in secondary paediatric units in South East England. Pediatr blood cancer,
Vol.49
(5),
pp. 678-681.
show abstract
BACKGROUND: The Paediatric Oncology Centres (POCs) treating childhood cancer in South East England produce unified supportive care guidelines for use in the secondary pediatric (shared care) units. This study evaluated the adherence to current guidelines for febrile neutropenia (FN) and documented outcome in terms of bacterial isolates, antibiotic resistance patterns, length of hospital stay, and mortality. PROCEDURE: Prospective study of pediatric FN admissions between July 2001 and December 2002. RESULTS: Data were received on 433 eligible FN episodes in 212 patients. The recommended empirical antibiotics (piptazobactam + gentamicin) were used in 354 (82%) admissions. Blood cultures were positive in 129 episodes (30%). Gram-positive organisms predominated (120/149 organisms isolated) and the majority were coagulase-negative Staphylococci (95/120). There were 27 Gram-negative isolates and 1 fungal isolate. No Gram-negative isolate was resistant to both first-line antibiotics. Only one death was recorded in the study group. The median length of hospital stay was 5 days. CONCLUSIONS: We obtained data on a large number of shared care episodes of FN. The antibiotic guidelines were followed in most episodes. Bacteremia was common, but little resistance to first-line antibiotics was documented among Gram-negative isolates, confirming the safety of the strategy in our population..
Fowler, D.J., Chisholm, J., Roebuck, D., Newman, L., Malone, M. & Sebire, N.J.
(2006). Melanotic neuroectodermal tumor of infancy: clinical, radiological, and pathological features. Fetal pediatr pathol,
Vol.25
(2),
pp. 59-72.
show abstract
We present a case of a 4-month-old female infant with a maxillary melanotic neuroectodermal tumor of infancy (MNTI) and review the pooled data from previous publications on this entity. The literature to date comprises 378 reported cases from 1918 to the present, from which data on the presence or absence of metastatic disease was available in 311, and on the presence or absence of local recurrence in 165. These pooled data suggest a local recurrence rate of 36% with metastasis occurring in 7% of cases. At present, the optimal management includes complete surgical excision with clear margins, but there are no reliable histopathological or molecular features to predict the biological behavior in individual cases..
Fowler, D.J., Malone, M., Chisholm, J., Roebuck, D. & Sebire, N.J.
(2006). Primary thoracic myxoid variant of extrarenal rhabdoid tumor in childhood. Fetal pediatr pathol,
Vol.25
(3),
pp. 159-168.
show abstract
Primary extrarenal rhabdoid tumors (RT) are now recognized as a specific entity in pediatric oncological pathology practice. We present an unusual case of a small cell myxoid variant of a thoracic RT in an infant and highlight the importance of recent molecular developments in the diagnosis of these tumors. An 8-month-old child presented with a short history of cough and shortness of breath. Imaging demonstrated a large mass occupying the majority of the thoracic cavity on the right side. A percutaneous needle biopsy of the mass showed fragments of tissue composed of malignant tumor with a predominant "small ovoid cell" phenotype and extensive myxoid change, with small nests and islands of tumor cells; occasional cells demonstrated open vesicular nuclei, prominent nucleoli, and eosinophilic cytoplasmic inclusions. Immunohistochemical staining revealed focal strong cytoplasmic positivity for cytokeratin, focal strong paranuclear cytoplasmic vimentin positivity, and INI1 staining showed normal nuclear positivity in control tissues but was negative in tumor cell nuclei. Electron microscopy demonstrated characteristic paranuclear whorls of intermediate filaments confirming the diagnosis of extrarenal malignant RT. The diagnosis of malignant rhabdoid tumor may be difficult, particularly in cases, such as the present, with a predominant small-cell myxoid phenotype. The characteristic expression patterns of cytokeratin and vimentin provide strong clues to the diagnosis, and the use of INI1 antibody now makes definitive diagnosis possible even on needle core biopsies..
Chisholm, J.C. & Dommett, R.
(2006). The evolution towards ambulatory and day-case management of febrile neutropenia. Br j haematol,
Vol.135
(1),
pp. 3-16.
show abstract
Febrile neutropenia (FN) is only second to chemotherapy administration as a cause of hospital admission during treatment for cancer. As FN may signify serious or life-threatening infection, management protocols have focussed on trying to prevent adverse outcomes in these patients. However, it is now possible to identify a subset of patients with FN at low risk of life-threatening complications in whom duration of hospitalisation and intensity of therapy can be reduced safely. This review discusses how the management of FN has evolved to enable patients identified as low risk to be treated on specific low risk management strategies, with an emphasis on some of the practical considerations for the implementation of such strategies..
Chisholm, J., Rubie, H., Desfachalles, S., Morland, B., Munzer, C., Valteau-Couanet, D., Mosseri, V., Bergeron, C., Weston, C., Coze, C., et al.
(2006). A Phase II study of Temozolomide in relapsed or refractory high-risk Neuroblastoma. Journal of clinical oncology,
(24(33)),
pp. 5259-5264.
Chisholm, J., Howe, K., Taj, M. & Zambon, M.
(2005). Influenza immunisation in children with solid tumours. European journal of cancer,
Vol.41
(15),
pp. 2280-2287.
Veal, G.J., Cole, M., Errington, J., Parry, A., Hale, J., Pearson, A.D., Howe, K., Chisholm, J.C., Beane, C., Brennan, B., et al.
(2005). Pharmacokinetics of dactinomycin in a pediatric patient population: a United Kingdom Children's Cancer Study Group Study. Clin cancer res,
Vol.11
(16),
pp. 5893-5899.
show abstract
PURPOSE: Dactinomycin (actinomycin D) is an antitumor antibiotic used routinely to treat certain pediatric and adult cancers. Despite concerns over the incidence of toxicity, little is known about the pharmacology of dactinomycin. A study was done to investigate dactinomycin pharmacokinetics in children. EXPERIMENTAL DESIGN: Dactinomycin was administered to 31 patients by bolus i.v. infusion, at doses of 0.70 to 1.50 mg/m2. Plasma concentrations were determined by liquid chromatography-mass spectrometry up to 24 hours after drug administration and National Cancer Institute Common Toxicity Criteria was assessed. RESULTS: Pharmacokinetic data analysis suggested that a three-compartment model most accurately reflected dactinomycin pharmacokinetics. However, there was insufficient data available to fully characterize this model. A median peak plasma concentration (Cmax) of 25.1 ng/mL (range, 3.2-99.2 ng/mL) was observed at 15 minutes after administration. The median exposure (AUC0-6), determined in 16 patients with sampling to 6 hours, was 2.67 mg/L.min (range, 1.12-4.90 mg/L.min). After adjusting for body size, AUC0-6 and Cmax were positively related to dose (P = 0.03 and P = 0.04, respectively). Patients who experienced any level of Common Toxicity Criteria grade had a 1.46-fold higher AUC0-6, 95% confidence interval (1.02-2.09). AUC0-6 was higher in patients <40 kg, possibly indicating a greater toxicity risk. CONCLUSIONS: Data presented suggest that dosing of dactinomycin based on surface area is not optimal, either in younger patients in whom the risk of toxicity is greater, or in older patients where doses are capped..
Tischkowitz, M.D., Chisholm, J., Gaze, M., Michalski, A. & Rosser, E.M.
(2004). Medulloblastoma as a first presentation of fanconi anemia. J pediatr hematol oncol,
Vol.26
(1),
pp. 52-55.
show abstract
Fanconi anemia is a chromosomal instability syndrome associated with certain congenital abnormalities, defective hemopoiesis, and an increased risk of developing acute myeloid leukemia and some solid tumors. The diagnosis can be made at birth if congenital abnormalities are present but is often made in childhood when hematologic complications develop. The authors report a case of Fanconi anemia diagnosed in a child with no congenital abnormalities and normal bone marrow who first presented with a cerebellar medulloblastoma. The authors discuss diagnostic and therapeutic implications for such malignancies in Fanconi anemia..
Little, M.A., Morland, B., Chisholm, J., Hole, A., Shankar, A., Devine, T., Easlea, D., Meyer, L.C. & Pinkerton, C.R.
(2002). A randomised study of prophylactic G-CSF following MRC UKALL XI intensification regimen in childhood ALL and T-NHL. Med pediatr oncol,
Vol.38
(2),
pp. 98-103.
show abstract
BACKGROUND: Despite the current widespread use of prophylactic G-CSF in children with solid tumours and leukaemia, its effectiveness has not been clearly demonstrated. This randomised study evaluates the role of G-CSF given after a 5-day intensification block in children with acute lymphoblastic leukaemia (ALL). PROCEDURE: Forty-six children with ALL or T-Cell non-Hodgkins lymphoma (NHL) treated on MRC ALL 97, UKALL XI or UKCCSG 9504 NHL protocols were randomised to receive granulocyte colony-stimulating factor following either the first or the second block of intensive chemotherapy in a cross-over study to determine if the prophylactic administration of G-CSF could reduce the rate of readmission to hospital for management of febrile neutropenia. RESULTS: There was a statistically significant difference in the rate of hospital admission in the group receiving prophylaxis, with 34 of 46 being admitted, compared to 42 of 46 patients in the control arm (74 vs. 91%; P=0.0386). There were no differences found in duration of hospital admission, haematological toxicity, neutrophil recovery or duration of supportive care between the two groups. There was no demonstrable cost benefit derived from the prophylactic administration of G-CSF. CONCLUSIONS: This study shows that the prophylactic administration of G-CSF following intensification chemotherapy for childhood ALL and T-NHL produces a significant reduction in the rate of readmission to hospital for the management of febrile neutropenia..
Chisholm, J.C., Devine, T., Charlett, A., Pinkerton, C.R. & Zambon, M.
(2001). Response to influenza immunisation during treatment for cancer. Arch dis child,
Vol.84
(6),
pp. 496-500.
show abstract
AIMS: To assess the annual risk of influenza infection in children with cancer and the immunogenicity of a trivalent split virus influenza vaccine in these children. METHODS: Eighty four children with cancer were tested for susceptibility to the circulating strains of influenza virus in autumn 1995 and 1996. Non-immunised children were reassessed the following spring for serological evidence of natural infection. Forty two patients received two doses of influenza vaccine. These children were receiving continuing chemotherapy for acute lymphoblastic leukaemia or were within six months of completing chemotherapy. RESULTS: Among the 84 children tested for influenza virus susceptibility only 8% of patients were fully protected (antibody titres >/= 40) against all three of the prevalent influenza virus strains; 33% were susceptible to all three viruses. Evidence of acquired natural infection was seen in 30% of unimmunised patients. Among immunised susceptible patients, 66% made some protective response to the vaccine and 55% showed protective antibody titres to all three viral strains following vaccination. Older age was associated with increased response to the H1N1 and H3N2 vaccine components, but total white cell count or neutrophil count at immunisation, type of cancer, or length of time on treatment for acute lymphoblastic leukaemia did not affect response. CONCLUSIONS: Most children with cancer studied were at risk of influenza infection. A significant response to immunisation was seen, supporting annual influenza vaccination for children being treated for cancer..
Chisholm, J., Devine, T., Dick, G., Mycroft, J. & Pinkerton, C.R.
(2000). Safety and tolerability of Amphotericin B Lipid Complex (Abelcet). International journal of pediatric hematology/oncology,
Vol.6
(6),
pp. 393-402.
Chisholm, J., Devine, T., Mycroft, J. & Pinkerton, C.R.
(1999). Liposomal amphotericin B (AmBisome) in children with febrile neutropenia and renal dysfunction. International journal of pediatric hematology/oncology,
Vol.6
(3),
pp. 173-182.
Chisholm, J.C., Devine, T., Mycroft, J. & Pinkerton, C.R.
(1998). Tolerability of amphotericin B lipid complex (ABELCET) in children with malignant disease. Bone marrow transplantation,
Vol.21,
pp. S145-S145.
Veys, P.A., Meral, A., Hassan, A., Goulden, N., Chisholm, J., New, H., Armstrong, J., Bennett-Rees, N., Webb, D. & Gerritsen, B., et al.
(1998). Improved outcome for blood and marrow transplantation in immunodeficiency. Bone marrow transplantation,
Vol.21,
pp. S128-S128.