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Biomedical subjects

B Morland

Publications and source records attributed to B Morland.

At least 19 recordsLinked to original sources
PubMed2007

Anaplastic large cell lymphoma of bone--is it a bad tumor?

A teenage boy presented with a CD30-positive anaplastic large cell lymphoma (ALCL) affecting his scapula and was successfully treated with chemotherapy. His clinical features and outcome were compared with other cases described in the literature. A further review of 11 ALCL cases with bony involvement treated in the UK since 1990, including two with primary bone disease, did not suggest an unfavorable treatment outcome. This finding will need to be confirmed by further study on a larger patient cohort with primary bone ALCL.

Activin Receptors, Type II↗
PubMed2007

Anaesthetic outcome and predictive risk factors in children with mediastinal tumours.

PURPOSE: The aims were to identify and test the significance of specific factors associated with risks for anaesthesia in children with mediastinal tumours. PATIENTS AND METHOD: Clinical information was retrospectively collected from the records of 63 children presented with mediastinal tumour (1964-2002) in a regional Paediatric Oncology centre and correlated with the type and outcome of anaesthesia, using non-parametric analyses. RESULTS: Thirteen patients had local anaesthesia or sedation for diagnostic procedures and none developed any complication. Fifty children received general anaesthesia (GA) for diagnostic investigations or tumour resection. Two patients were excluded from the analysis because of treatment prior to GA. Problems with intubation, ventilation and cardiovascular collapse were encountered in 7 of 48 (15%) patients and this resulted in tracheostomy in one patient and death in 2 other cases. When compared with the 41 uncomplicated cases, the presence of at least 3 respiratory symptoms/signs, tracheal and vascular compression, and infection significantly increased the risk of GA. Of these, tracheal compression remained the strongest predictive factor. CONCLUSIONS: Decision to postpone GA should be considered if all these risk factors (tracheal compression, vascular compression, the presence of at least three respiratory symptoms/signs) are present in the same patient.

Adolescent↗
PubMed2004

European collaboration in trials of new agents for children with cancer.

Childhood cancer is a relatively rare disease, representing just 1% of all malignancies. Within Europe, this represents some 12,000 new cases each year, with approximately 1600 a year in the United Kingdom and 1800 in France. International collaboration in phase III trials of childhood cancer has been the norm for many years, traditionally within Europe, but, largely because of organisational considerations, phase I and II trials have only been conducted on a national basis. With overall cure rates in the region of 70%, relatively few children are available for these early drug trials. Access to new drugs is also a major problem. Against this background, a United Kingdom (UK)/French 'new agent' collaboration was established, expanding subsequently into a wider European grouping. This paper documents the history of that collaboration, the outcomes and future challenges.

Antineoplastic Agents↗
PubMed2003

Viridans streptococcus bacteremia in children on chemotherapy for cancer: an underestimated problem.

The authors discuss the morbidity associated with viridans streptococcus bacteremia, and its implications on the choice of antibiotics used as prophylaxis and treatment. They retrospectively studied the case notes of 38 children who were being treated for various malignant conditions in their unit and developed 40 episodes of bacteremia with viridans streptococci between October 1995 and January 1999. Viridans streptococci were the third commonest blood culture isolate during this period, after coagulase-negative staphylococci and Staphylococcus aureus. The majority of the isolates were Streptococcus mitis (55%). Others were S. sanguis (25%), S. oralis (12.5%), S. salivarius (5%), and S. acidominimus (2.5%). Twenty-five percent of the patients had been treated with regimens that included cytosine arabinoside, 60% were receiving prophylactic co-trimoxazole, and 87.5% were neutropenic. Thirty percent of patients had abnormal chest X-rays, and 15% were hypotensive; 2 patients required admission to the intensive care unit. Initial antibiotic therapy was changed because of failure of clinical response in 60% of cases, despite the infecting organism being sensitive in vitro. This study confirms the importance of viridans streptococci as a cause of bacteremia in pediatric hematology and oncology patients, leading to significant morbidity. Further work is required to establish the optimal treatment for viridans streptococcus bacteremia.

Adolescent↗
PubMed2002

A randomised study of prophylactic G-CSF following MRC UKALL XI intensification regimen in childhood ALL and T-NHL.

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.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Strategy for hepatoblastoma management: Transplant versus nontransplant surgery.

BACKGROUND: Liver transplantation now is proposed for managing selected hepatoblastoma cases. Indications are not yet well defined. METHODS: The case records of 34 children with hepatoblastoma treated over a period of 10 years (1991 to 2000) were reviewed retrospectively. RESULTS: All patients benefited from preoperative chemotherapy. Twenty patients underwent major hepatic resections. Twelve patients, in absence of residual metastasis, underwent liver transplant because the tumour remained unresectable after chemotherapy. Two patients who presented with recurrence after a right hepatectomy, benefited from transplant as a second option. Two other patients did not undergo surgery because of widespread disease or resistance to chemotherapy. Disease-free survival rates were 95% after surgical resection, 100% when primary transplant was performed in patients with good response to chemotherapy, 60% after transplantation in patients with poor response to chemotherapy, 50% in patients with transplant as second option, and 0% in patients not undergoing surgery. CONCLUSIONS: Transplantation is a potentially curative option for unresectable hepatoblastoma when chemosensitive (decrease in alpha-fetoprotein and decrease in tumour size). In this context, also favourable cases with good response but difficult resections with doubtful margins of resection may best be proposed for primary transplantation. Patients with recurrent or resistant disease are not good candidates.

Antineoplastic Agents↗
PubMed2001

A phase I study in paediatric patients to evaluate the safety and pharmacokinetics of SPI-77, a liposome encapsulated formulation of cisplatin.

Pre-clinical studies indicate that cisplatin encapsulated in STEALTH((R))liposomes (SPI-77) retains anti-tumour activity, but has a much reduced toxicity, compared to native cisplatin. A phase I study was conducted to determine the toxicity and pharmacokinetics of SPI-77 administered to children with advanced cancer not amenable to other treatment. Paediatric patients were treated at doses ranging from 40 to 320 mg m(-2)by intravenous infusion every 4 weeks. Blood samples taken during, and up to 3 weeks after, administration and plasma and ultrafiltrate were prepared immediately. Urine was collected, when possible, for 3 days after administration. SPI-77 administration was well tolerated with the major toxicity being an infusion reaction which responded to modification of the initial infusion rate of SPI-77. Limited haematological toxicity and no nephrotoxicity were observed. No responses to treatment were seen during the course of this phase I study. Measurement of total plasma platinum showed that cisplatin was retained in the circulation with a half life of up to 134 h, with maximum plasma concentrations approximately 100-fold higher than those reported following comparable doses of cisplatin. Comparison of plasma and whole blood indicated that cisplatin was retained in the liposomes and there was no free platinum measurable in the ultrafiltrate. Urine recovery was less than 4% of the dose administered over 72 h. Results from this phase I study indicate that high doses of liposomal cisplatin can safely be given to patients, but further studies are required to address the issue of reformulation of liposomally bound cisplatin.

Adolescent↗
PubMed2001

A phase I study of nolatrexed dihydrochloride in children with advanced cancer. A United Kingdom Children's Cancer Study Group Investigation.

A phase I study of nolatrexed, administered as a continuous 5 day intravenous infusion every 28 days, has been undertaken for children with advanced malignancy. 16 patients were treated at 3 dose levels; 420, 640 and 768 mg/m(2)24 h(-1). 8 patients were evaluable for toxicity. In the 6 patients treated at 768 mg/m(2)24 h(-1), dose-limiting oral mucositis and myelosuppression were observed. Plasma nolatrexed concentrations and systemic exposure, measured in 14 patients, were dose related, with mean AUC values of 36 mg(-1)ml(-1)min(-1), 50 mg ml(-1)min(-1)and 80 mg ml(-1)min(-1)at the 3 dose levels studied. Whereas no toxicity was encountered if the nolatrexed AUC was <45 mg ml(-1)min(-1), Grade 3 or 4 toxicity was observed with AUC values of >60 mg ml(-1)min(-1). Elevated plasma deoxyuridine levels, measured as a surrogate marker of thymidylate synthase inhibition, were seen at all of the dose levels studied. One patient with a spinal primitive neuroectodermal tumour had stable disease for 11 cycles of therapy, and in two patients with acute lymphoblastic leukaemia a short-lived 50% reduction in peripheral lymphoblast counts was observed. Nolatrexed can be safely administered to children with cancer, and there is evidence of therapeutic activity as well as antiproliferative toxicity. Phase II studies of nolatrexed in children at the maximum tolerated dose of 640 mg/m(2)24 h(-1)are warranted.

Acute Disease↗
PubMed2000

Prospective validation of renal function-based carboplatin dosing in children with cancer: A United Kingdom Children's Cancer Study Group Trial.

PURPOSE: Carboplatin dosing in adults with cancer is based on renal function. The purpose of the current study was to validate a previously developed pediatric carboplatin-dosing formula. PATIENTS AND METHODS: Thirty-eight pediatric patients were randomized to receive a carboplatin dose calculated according to surface area or a renal function-based dosing formula. On the next course of therapy, the alternative dosing method was used for each patient. Carboplatin pharmacokinetics (based on free plasma platinum concentrations) were measured after both courses. RESULTS: The mean observed areas under the carboplatin concentration-versus-time curve (AUCs) after renal function- and surface area-based dosing were 98% and 95% of the target AUCs, respectively. The variation in the observed AUC was significantly less after renal function-based dosing (F test, P =.02), such that 74% of courses had an observed AUC within +/- 20% of the target value, versus 49% for courses after dosing according to surface area. Only one of 22 courses at the center with the most experience with renal function-based dosing was associated with an AUC outside +/- 20% of the target value, versus nine of 22 courses after surface area-based dosing in the same center. There was a relationship (r(2) =.71) between carboplatin AUC and thrombocytopenia in 10 neuroblastoma patients treated with a combination of carboplatin, vincristine, etoposide, and cyclophosphamide. CONCLUSION: Renal function-based carboplatin dosing in children results in more consistent drug exposure than surface area-based drug administration.

Adolescent↗
PubMed1999

Orthotopic liver transplantation for unresectable hepatoblastoma: a single center's experience.

BACKGROUND/PURPOSE: Complete surgical resection after chemotherapy is the definitive treatment for hepatoblastoma. However, orthotopic liver transplantation (OLT) is now accepted as a treatment modality for patients with unresectable tumours. The aim of this study was to review a single center's experience of OLT for unresectable hepatoblastoma. METHODS: A retrospective review of 8 patients with unresectable hepatoblastoma who were referred for liver transplantation was conducted. RESULTS: The patients assessed had an age range of 5 to 105 months at presentation; median, 24 months, (5 boys; 3 girls). Two patients have familial adenomatous polyposis, and one has right hemihypertrophy. All 8 patients had received standard chemotherapy according to SIOP (International Society of Pediatric Oncology) protocols. Extrahepatic metastases were found in 3 patients at diagnosis, but none had detectable metastases at the time of OLT. Four patients continued chemotherapy while awaiting OLT. Three patients received whole grafts, and 5 received reduced grafts. The median follow-up period was 22 months (range, 2 to 78 months). Five patients are alive and well, although 1 patient had a second OLT for biliary cirrhosis secondary to biliary stricture at 6 years. Three patients died: one 26 days post OLT of sepsis and two of disease recurrence at 22 months and 70 months posttransplant. The actuarial survival rate is 88% and 65% at 1 and 5 years, respectively, whereas the overall survival rate is 62.5%. CONCLUSION: OLT for unresectable hepatoblastoma without extra hepatic metastases is highly successful with a low recurrence rate.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Phase I study of temozolomide in paediatric patients with advanced cancer. United Kingdom Children's Cancer Study Group.

A phase I study of temozolomide administered orally once a day, on 5 consecutive days, between 500 and 1200 mg m(-2) per 28-day cycle was performed. Children were stratified according to prior craniospinal irradiation or nitrosourea therapy. Sixteen of 20 patients who had not received prior craniospinal irradiation or nitrosourea therapy were evaluable. Myelosuppression was dose limiting, with Common Toxicity Criteria (CTC) grade 4 thrombocytopenia occurring in one of six patients receiving 1000 mg m(-2) per cycle, and two of four patients treated at 1200 mg m(-2) per cycle. Therefore, the maximum-tolerated dose (MTD) was 1000 mg m(-2) per cycle. The MTD was not defined for children with prior craniospinal irradiation because of poor recruitment. Plasma pharmacokinetic analyses showed temozolomide to be rapidly absorbed and eliminated, with linear increases in peak plasma concentrations and systemic exposure with increasing dose. Responses (CR and PR) were seen in two out of five patients with high-grade astrocytomas, and one patient had stable disease. One of ten patients with diffuse intrinsic brain stem glioma achieved a long-term partial response, and a further two patients had stable disease. Therefore, the dose recommended for phase II studies in patients who have not received prior craniospinal irradiation or nitrosoureas is 1000 mg m(-2) per cycle. Further evaluation in diffuse intrinsic brain stem gliomas and other high-grade astrocytomas is warranted.

Adolescent↗
PubMed1997

Granulocyte colony-stimulating factor in established febrile neutropenia: a randomized study of pediatric patients.

PURPOSE: Infection in neutropenic patients is potentially life-threatening and carries important implications for hospital resource use. Prophylactic administration of cytokines may reduce the severity of neutropenia, but involves the treatment of all patients for the possible benefit of a minority. This study evaluates whether treatment with cytokines in the setting of established febrile neutropenia will influence outcome and be potentially more cost-effective. PATIENTS AND METHODS: In a double-blind study, pediatric patients with fever and severe neutropenia were randomized to receive granulocyte colony-stimulating factor ([G-CSF] filgrastim; 5 microg/kg/d) or placebo, in addition to antibiotics. The study protocol required a resolution of fever and a neutrophil count > or = 0.2 x 10(9)/L for hospital discharge. Patients could be randomized for up to four independent febrile episodes. A total of 186 episodes of febrile neutropenia were investigated. RESULTS: Patients randomized to G-CSF had a shorter hospital stay (median, 5 v 7 days; P = .04) and fewer days of antibiotic use (median, 5 v 6 days; P = .02). G-CSF-treated patients also had more rapid neutrophil recovery and higher neutrophil levels at discharge. The 2-day reduction in hospital stay reduced the median bed cost by 29% per patient admission (P = .04). CONCLUSION: Under the clinical guidelines of our institution, the use of G-CSF in the treatment of established febrile neutropenia produced a small but significant reduction in the time that children required antibiotics and hospital admission, with possible cost savings.

Anti-Bacterial Agents↗
PubMed1995

Lymphadenopathy.

Explore the source record for details and available documents.

Bacterial Infections↗
PubMed1994

Synovial sarcoma of the larynx in a child: case report and histological appearances.

Synovial sarcoma of the larynx is extremely rare having been reported only six times previously in the literature. We add another case report, which to our knowledge is the first recorded case in a child. We discuss the alternative approach of combination chemotherapy and radiotherapy which in this case led to a remission lasting about 3 years. The immunohistological and ultrastructural characteristics of the tumour are also presented.

Adolescent↗
PubMed1992

Effectiveness of combinations of bispecific antibodies for delivering saporin to human acute T-cell lymphoblastic leukaemia cell lines via CD7 and CD38 as cellular target molecules.

We have investigated the effectiveness of three different F(ab' gamma)2 bispecific antibodies (BsAb) for delivering the ribosome inactivating protein (RIP) saporin via the CD7 or CD38 cell surface molecules to the human T-ALL cell lines HSB-2 and HPB-ALL. Inhibition of 3H-leucine uptake by target cells was used as the parameter of cellular cytotoxicity. Used singly against HSB-2 cells in the presence of varied concentrations of saporin, an anti-CD7 BsAb, (HB2 x DB7-18) and an anti-CD38 BsAb (OKT10 x RabSap), gave 435- and 286-fold increases in saporin toxicity, respectively. For HPB-ALL cells the anti-CD7 BsAb performed poorly giving only an eight-fold increase in toxicity whilst on the same cell line the anti-CD38 BsAb was highly potent giving an 80,000-fold increase in saporin toxicity. A combination of both BsAb used together against HSB-2 cells was ten times more effective, than the best single BsAb HB2 x DB7-18 used alone. Kinetic studies conducted with HSB-2 cells revealed that the BsAb combination also gave an increased rate of protein synthesis inactivation in comparison to either BsAb used alone. These investigations clearly demonstrate a synergistic action when both BsAb are used in combination to target saporin against CD7 and CD38 expressed on the surface of the HSB-2 cell line.

ADP-ribosyl Cyclase↗
PubMed1991

Characteristics and performance of a bispecific F (ab'gamma)2 antibody for delivering saporin to a CD7+ human acute T-cell leukaemia cell line.

We have investigated the efficacy of a F(ab'gamma)2 bispecific antibody (BsAb) with dual specificity for the CD7 molecule in one Fab arm and for the ribosome inactivating protein (rip) saporin in the other arm, for delivering saporin to the acute T-cell leukaemia cell line HSB-2. Saporin titration experiments revealed that BsAb increased the toxicity of saporin 435-fold for HSB-2 cells, reducing the IC50 for saporin alone from 0.1 mumol to 0.23 nmol when BsAb was included. The rate of protein synthesis inactivation brought about by BsAb-mediated toxin delivery to HSB-2 cells was very similar to that described for conventional immunotoxins (IT's) with a t10 (time taken for a one log inhibition of protein synthesis compared with controls) of 46 h obtained at a saporin concentration of 1 nmol and 226 h at 0.1 nmol. BsAb titration studies demonstrated a clear dose response effect of BsAb concentration on target cell protein synthesis inhibition and cell proliferation. The absolute specificity of toxin delivery was unequivocally demonstrated by a failure of BsAb to deliver an effective dose of saporin to the CD7- cell line HL60 and by the blocking of BsAb-mediated delivery of saporin to HSB-2 cells with an excess of F(ab)2 fragments of the anti-CD7 antibody, HB2. These studies have clearly demonstrated the effectiveness of this BsAb for delivering saporin to a T-ALL cell line utilising CD7 as the target molecule on the cell surface. BsAb's would therefore appear to offer a realistic alternative to IT's for toxin delivery to tumour cells and may even offer certain advantages over conventional IT's for clinical use.

Antibodies, Monoclonal↗