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F Wesenberg

Publications and source records attributed to F Wesenberg.

At least 19 recordsLinked to original sources

Children with acute lymphoblastic leukaemia have high plasma levels of total homocysteine at time of diagnosis.

OBJECTIVE: Cancer can induce venous thromboembolic complications for various reasons. As part of a greater study, acquired and congenital prothrombotic risk factors were investigated in children with leukaemia or non-Hodgkin's lymphoma and compared with similar investigations in children with congenital heart defects. MATERIAL AND METHODS: Blood samples were taken from 60 children with newly diagnosed leukaemia or lymphoma and 133 children with congenital heart defects in the course of a scheduled cardiac catheterization. When children with cancer were in remission, analyses of acquired prothrombotic risk factors were repeated. Children with cancer were observed for symptoms of thromboembolism throughout their treatment period. RESULTS: Total homocysteine levels were significantly raised in children with cancer (median value 10.0 micromol/L) as compared with the levels in children with congenital heart diseases (5.0 micromol/L) (p<0.001), while children with acute lymphoblastic leukaemia had the highest values. The median level of lipoprotein(a) was slightly increased in children with newly diagnosed leukaemia or lymphoma (105 mg/L versus 100 mg/L, p<0.001), and levels of coagulation inhibitors were higher (p<0.001). Total homocysteine levels normalized when children attained remission of cancer disease. Two children had symptoms of acute thrombosis. CONCLUSIONS: Raised concentrations of total homocysteine were frequent in children with newly diagnosed cancer, but this normalized when the children were in remission. The clinical significance of our observations and the impact on venous thromboembolism have yet to be defined.

Adolescent↗

Deletion of the Ink4-locus (the p16ink4a, p14ARF and p15ink4b genes) predicts relapse in children with ALL treated according to the Nordic protocols NOPHO-86 and NOPHO-92.

Inactivation of the Ink4 gene locus locus on 9p comprising the tumour suppressor gene p16ink4a and its neighbours p14ARF and p15ink4b is common in childhood acute lymphoblastic leukaemia (ALL), but the prognostic significance is controversial. DNA from 230 patients was retrospectively analysed by Southern blotting, single strand conformation polymorphism (SSCP) and sequencing techniques. The results were correlated with clinical characteristics and outcome. One hundred and ninety-four fully analysed patients, similarly treated using the Nordic NOPHO-86 or the current NOPHO-92 protocols, were included in the outcome analysis. Deletions approached a minimally deleted region between the p16ink4a and p15ink4b genes, making the p14ARF gene the most commonly deleted coding sequence. Bi-allelic deletion was associated with high white blood cell count (WBC) (P < 0.001), T cell phenotype (P < 0.001) and mediastinal mass (P < 0.001). Patients with Ink4 locus bi-allelic deletions had an inferior pEFS (P < 0.01) and multivariate analysis indicated that bi-allelic deletion of the p16ink4a and the p14ARF genes was an independent prognostic risk factor (P < 0.05). Sub-group analysis revealed a pronounced impact of deletion status for high-risk patients, ie with high WBC. Deletion-status and clinical risk criteria (WBC) could thus be combined to further differentiate risk within the high-risk group. The analysis of the Ink4 locus adds independent prognostic information in childhood ALL treated by Nordic protocols and may help in selection of patients for alternative treatment.

Antineoplastic Combined Chemotherapy Protocols↗

Adverse drug events in children during hospitalization and after discharge in a Norwegian university hospital.

UNLABELLED: The frequency and characteristics of adverse drug events (ADEs) in children hospitalized in the paediatric department of Ullevaal University Hospital, Norway, were determined using intensive monitoring. Of 579 children treated with drugs, 28% experienced ADEs; 7% at the time of admission, 18% during hospitalization and 9% after discharge. All children treated for cancer, 19% treated with anti-infective drugs, 15% treated with antiasthmatics and 10% treated with drugs affecting the nervous system experienced ADEs. The most frequent events were gastrointestinal, CNS- and skin reactions and 19% were considered as serious. ADEs caused 6% of the admissions and 44% required interventions. Most ADEs were found by screening patient records, where physicians mostly described adverse drug events requiring interventions and nurses described less serious events. Parents reported 14% of the events, of which a majority were CNS reactions. CNS reactions may be more common than expected and observations by parents are important when investigating such reactions in children. CONCLUSIONS: ADEs, mainly gastrointestinal, CNS and skin reactions related to drugs affecting the nervous system, anti-infectives and antiasthmatics, were seen in 28% of the patients. The reporting of events by parents was a useful supplement to the screening of patient records.

Adolescent↗

Ependymoma in children and young adults (0-19 years): report of 25 consecutive cases.

The objective of this retrospective study was to evaluate the relative effect of surgery and radiotherapy (RT) on the survival of 25 consecutive children and young adults treated for ependymoma [18 in the posterior fossa (PF), 2 in supratentorial locations (ST) and 5 in intraspinal locations (IS)]. Five-year survival rates for patients with PF, ST and IS tumors were 28%, 0% and 100%, respectively. Total tumor resection was a positive prognostic factor in the case of PF tumors. No patients with subtotal removal of a PF tumor survived for longer than 5 years. The effect of RT on survival of patients with PF ependymomas in this series was uncertain. No patients with PF ependymoma had disseminated disease at diagnosis, and all tumor recurrences were local. Based on these observations, we see no indications for craniospinal RT of PF ependymomas, except in rare cases of disseminated disease. If RT is given, it should only be targeted to the tumor site. The two patients with ST ependymoma died within 3.8 years after primary treatment. Our series of ST ependymomas does not allow any specific treatment recommendations. One patient with IS ependymoma was cured by surgery alone. Four patients with IS ependymoma had documented residual tumor after surgery. RT induced remission in these patients. For IS ependymomas we recommend no RT if total tumor removal can be documented. In patients with subtotal removal of IS ependymomas local RT is effective and should be given.

Adolescent↗

Rational use of blood products.

Blood product transfusions can be life saving and must be considered in the supportive care of children of any age with underlying oncological or haematological problems, as well as after major surgery or after serious trauma. Paediatric transfusions are particularly challenging because life-long effects of transfusion complications are more durable and serious in children than in adults, in whom the median age at transfusion is >70 years (Tynell E, Norda R, Shanwell A, Björkman A. Long-term survival in transfusion recipients in Sweden, 1993. Transfusion 2001, 41, 251-255). While the general indications for transfusions in paediatric patients are similar to adults, the threshold, volumes and infusion rates for transfusions vary with age. In this Update, we discuss current blood products, then suggest transfusion "triggers" in major surgery and haematological and oncologic practice. Finally, future developments and new possibilities are considered.

Blood Component Transfusion↗

Microcephalus, medulloblastoma and excessive toxicity from chemotherapy: an unusual presentation of Fanconi anaemia.

UNLABELLED: Fanconi anaemia is a genetically and phenotypically heterogeneous disorder with different forms of clinical presentation. In this case the patient had suffered from microcephalus and delayed motor development from birth, but extensive investigation did not disclose any aetiology. At 3.5 y she developed a cerebellar medulloblastoma which was treated with surgery and chemotherapy. Following chemotherapy with alkylating agents she suffered from severe bone marrow aplasia which caused life-threatening infections, feeding problems and impaired kidney function. Fanconi anaemia was suspected, but it took 2 mo before the chromosome fragility test came out positive. From the moment diagnosis of Fanconi anaemia was made, no further active treatment was given. The patient's condition improved for some time, but she relapsed and died exactly 1 y after the first diagnosis of brain tumour. CONCLUSION: Fanconi anaemia must always be suspected in patients who experience excessive toxicity from chemotherapy regardless of the type of malignancy and congenital malformations.

Antineoplastic Combined Chemotherapy Protocols↗

Competitive PCR for quantification of minimal residual disease in acute lymphoblastic leukaemia.

A very precise and reproducible polymerase chain reaction (PCR) method was developed in order to quantify minimal residual disease (MRD) in children with acute lymphoblastic leukaemia (ALL). A clone-specific competitor was constructed by introducing a restriction site in a PCR product identical to parts of the highly specific rearranged T-cell receptor delta (TCR-delta), T-cell receptor gamma (TCR-gamma), or immunoglobulin heavy chain (IgH) genes of the malignant clone. Using primers located externally to the restriction site the competitor and the DNA from the malignant clone will be amplified under identical conditions. After restriction enzyme cleavage, the PCR products originating from the competitor and the malignant clone can be distinguished by size in a gel electrophoresis step and the amount of residual disease can be determined. The method is very sensitive with a detection limit of at least one malignant cell in 10(5) normal cells. This method may be used for treatment stratification based on the early response to antileukaemic therapy.

Adolescent↗

Acremonium strictum fungaemia in a paediatric patient with acute leukaemia.

A 7-y-old boy with relapsed acute lymphatic leukaemia developed fungaemia due to Acremonium strictum, a fungus belonging to the group of the hyaline hyphomycetes. Initially, the fungus was misdiagnosed as Candida sp. due to the presence of abundant adventitious forms. At the time of diagnosis the patient was neutropenic and had a central venous catheter (CVC) in situ. The formation of an occlusive thrombotic mass in the v. subclavia dextra complicated the infection. Treatment consisted of amphotericin B, fluconazole, granulocyte colony-stimulating factor (G-CSF) and removal of the CVC. However the patient responded clinically only after the intravascular thrombus had been removed surgically. Amphotericin B, voriconazole and terbinafine showed high activity in vitro against the Acremonium isolate. A literature review revealed 5 other immunocompromised paediatric patients with a systemic or localized infection due to Acremonium spp.

Acremonium↗

Posterior fossa medulloblastoma in children and young adults (0-19 years): survival and performance.

The objective of this study was to present survival data and outcome status in the long-term survivors of a consecutive series of 111 children and young adults treated for posterior fossa medulloblastoma in our departments from 1960 to 1997. The total surgical mortality was 13%. The surgical mortality rate declined significantly during the time period overall, from 23% before 1970 to 0% after 1990. The 5-year survival rate for patients treated between 1960 and 1973 was 0%, while 5-year survival for patients treated after the introduction of systematic craniospinal radiation in 1974 was 53%. Thirty-four patients were alive at the close of this study, with a mean observation time of 13.5 years. Over half, 61%, of the patients had one or more major deficits/problems with respect to learning ability, power of locomotion, sociability, hobbies and relationships with the opposite sex. A younger age at the time of treatment was correlated with larger deficits/problems in these variables. The correlation between young age at the time of treatment and short final height was significant. The frequency of a second neoplasm was 14%. In all but 3 cases the major cause of permanent deficits/problems was radiation therapy.

Adolescent↗

[High dose therapy with autologous stem cell support in malignant disorders. Excerpt from the statement by the advisory group of the State Health Services].

New biomedical knowledge may improve the diagnostic procedures and treatment provided by the Health Services, but at additional cost. In a social democratic health care system, the hospital budgets have no room for expensive, new procedures or treatments, unless these are funded through extra allocation from the central authorities. High dose therapy with autologous stem cell support in malignant disorders is an example of a new and promising, but rather expensive treatment, but its role in cancer therapy has yet to be established. The indications for testing high dose therapy with autologous stem cell support in various malignancies are discussed, with emphasis on the principles for deciding which categories of disease should have priority. The authors suggest some malignant disorders for which high dose therapy with stem cell support should be explored versus conventional treatment in randomised prospective trials.

Cost-Benefit Analysis↗

[Investigation and treatment of immune thrombocytopenic purpura in children in Norway].

The treatment of immune thrombocytopenic purpura (ITP) in children has been debated for a long time. Some years ago the Norwegian paediatric haematology and oncology group proposed guidelines for investigation and therapy. In order to assess the present management of ITP in Norway, we sent a questionnaire to all paediatric departments. Answers from 22 departments could be analyzed. The estimated number of new ITP cases was 54, giving an incidence of 6.7 per 100,000 children. Most of the departments treat only a few patients (one to three patients a year). Investigation and treatment of ITP follows roughly the Norwegian guidelines. Disagreement exists about the indication for start of drug treatment (the lowest accepted platelet count differed from < 5 to 30 x 10(9)/l) and about choice of drug (1/2 prefer steroids, 2/3 immunoglobulins). There seems to be great interest for this topic among the Norwegian pediatricians. A prospective registration of all ITP cases in Norway has now been started.

Child↗

Outcome after first relapse in children with acute lymphoblastic leukemia: a population-based study of 315 patients from the Nordic Society of Pediatric Hematology and Oncology (NOPHO).

UNLABELLED: This study reports the outcome after relapse of acute lymphoblastic leukemia (ALL) in a population-based study of 809 children over 1 year of age diagnosed July 1981 through June 1986 and with non-B acute lymphoblastic leukemia in the five Nordic countries. By January 1994, 315 children had suffered at least one relapse. The bone marrow was involved in 216 cases. There were 69 isolated CNS relapses, 25 isolated testicular recurrences and five relapses in other extramedullary sites. Of the 315 children with relapse, 94 are still in a second complete remission 12-138 (median: 78) months after relapse. The overall probability of a second event free survival (P-2.EFS) and survival after relapse was 0.28 and 0.33 respectively. The probability of remaining in second remission at 11 years was significantly correlated to the duration of first remission (P < 0.001), the site of relapse (P < 0.001) and gender (P = 0.004). The P-2.EFS for early, intermediate, and late bone marrow involved relapses were 0.08, 0.19, and 0.50 respectively. For early, intermediate and late isolated CNS relapses the P-2.EFS were 0.21, 0.38 and 0.61, respectively. The P-2.EFS for boys with isolated testicular relapses was 0.69. Girls with isolated CNS relapse (P < 0.001) and with bone marrow involved relapse (P = 0.04) had a significantly better prognosis than boys. Children with initial high risk criteria, especially T-ALL and mediastinal mass who relapsed, had a very poor prognosis. CONCLUSION: In this population-based study, about 30% of children with ALL obtained a long second remission and possible cure.

Adolescent↗

Plasma homocysteine in children with acute lymphoblastic leukemia: changes during a chemotherapeutic regimen including methotrexate.

Plasma homocysteine was determined in 12 children with acute lymphoblastic leukemia. The patients were investigated prior to chemotherapy (stage I), during seven weeks of induction chemotherapy (stage II), and thereafter during intermittent high-dose methotrexate (HD-MTX) therapy (stage III). The patients were followed for a period of three to 15 months, and the study included a total of 80 HD-MTX courses. Before start of chemotherapy (stage I), the average plasma homocysteine level in the children with leukemia was 13.18 +/- 6.23 (SD) mumol/liter, which is significantly (P less than 0.001) higher than the level in control children (6.52 +/- 1.21 mumol/liter). The plasma homocysteine level in the patients was positively correlated with the peripheral white blood cell count (P less than 0.01) and negatively correlated with serum folate (P less than 0.02). The serum folate was normal or subnormal in these patients. During induction therapy with cytotoxic drugs such as vincristine, asparaginase, and intrathecal MTX (stage II), there was a drastic change in plasma homocysteine as a function of time. A reciprocal alteration in serum folate was observed, suggesting fluctuating intracellular folate status at this stage of therapy. At the end of stage II (about seven weeks), there was a significant (P less than 0.01) reduction in total homocysteine (to 7.08 +/- 3.84 mumol/liter). HD-MTX (8 g/m2) therapy with 5-formyltetrahydrofolate "rescue" (stage III) was usually begun about seven weeks after start of chemotherapy, and the patients were followed for two to eight courses separated by three to eight weeks. Plasma homocysteine showed a transient increase (26-64%) following each MTX infusion. After three MTX infusions, basal total plasma homocysteine was reduced to 5.56 +/- 1.12 mumol/liter. During most MTX infusions, there was a variable reduction (17-56%) in plasma methionine followed by a rebound increase. It is concluded that plasma homocysteine in children with acute lymphoblastic leukemia is elevated prior to therapy, probably because of occasional folate deficiency and increased burden of proliferating cells. During induction therapy, monitoring plasma homocysteine and serum folate both suggest a labile folate homeostasis, usually a deficiency state. HD-MTX induced a temporary intracellular folate depletion before 5-formyl-tetrahydrofolate was administered, as judged by a transient homocysteinemia. The methionine depletion may interfere with the antileukemic effect of MTX.

Adolescent↗

How much is too much? Folinic acid rescue dose in children with acute lymphoblastic leukaemia.

The effect of folinic acid rescue dose on the event-free survival of 71 children with acute lymphoblastic leukaemia was examined in a retrospective clinical study. All patients, diagnosed between 1 January 1980 and 1 January 1989, were treated according to the Norwegian Pilot protocol which included eight courses of high dose (6-8 g/m2/24 h intravenous infusion) methotrexate. Following the infusion, a uniform dose of 75 mg (at 36 h after the beginning of the drug infusion) and 15 mg (at 39-106 h) folinic acid rescue was administered to all patients, at predetermined intervals. The uniformity of the rescue dose resulted in distribution of dosages in the range of 38-140 mg/m2 and 7.5-28 mg/m2 for the different periods, respectively, when the dose was recalculated on the basis of the body surface area of the individual patients. The event-free survival of children receiving less or more than 15 mg/m2 (75 mg/m2) rescue dose was compared. Although no significant difference was found, a tendency was observed for a lower risk of relapse in patients receiving less folinic acid. No major methotrexate-related toxicity was observed in the group of patients receiving the lower dose of rescue. These observations suggest that the reduction of folinic acid rescue dose below the generally accepted 12-15 mg/m2 dose may increase the efficacy of high-dose methotrexate therapy while still remaining safe in preventing treatment-related toxicity. Prospective, randomised clinical trials are needed to examine the role of rescue as a determinant of effective exposure to methotrexate in patients receiving high-dose methotrexate treatment.

Adolescent↗

Antibodies to staphylococcal peptidoglycan and its peptide epitopes, teichoic acid, and lipoteichoic acid in sera from blood donors and patients with staphylococcal infections.

Antibodies to the staphylococcal antigens peptidoglycan, beta-ribitol teichoic acid, and lipoteichoic acid, as well as to the peptidoglycan epitopes L-Lys-D-Ala-D-Ala, L-Lys-D-Ala, and pentaglycine, were found over a wide range of concentrations in sera from both blood donors and patients with verified or suspected staphylococcal infections. The patient group was heterogeneous with regard to both age and type of staphylococcal infections, being representative for sera sent to our laboratory. In single-antigen assays antibodies to pentaglycine had the highest predictive positive value (67%), although only 32% of the patients had elevated levels of such antibodies. Combinations of test antigens could yield positive predictive values as high as 100%, but then the fraction of positive sera was low. Indeed, the fraction of patient sera which was positive in multiple-antigen tests never exceeded 61%. The clinical usefulness of these seroassays for identifying Staphylococcus aureus as a causative agent was limited, owing to the considerable overlap in the range of antibody concentrations between patient and blood donor sera.

Adolescent↗

Structural chromosome aberrations in lymphocytes from children previously treated for Wilms' tumor or Hodgkin's disease.

Nineteen children treated for Wilms' tumor (thirteen cases) or Hodgkin's disease (six cases) with cytostatic agents and/or radiotherapy were studied cytogenetically on lymphocytes cultivated from blood samples drawn after at least 1 year of complete remission after end of therapy. A reference group of children was matched for age, sex, and residence. The frequencies of sister chromatid exchange (5.4 versus 5.6 SCE/cell), and chromosome damage type gaps (6.6 versus 7.1%) and breaks (1.9 versus 1.9%) were not different in the two groups, but exchange type aberrations were more frequent in the patients (0.9 versus 0.06%). Fifty karyotypes were analyzed in all but two cases of Hodgkin's disease. The overall frequency of stable (3.1 versus 3.8%) and unstable (1.7 versus 1.4%) structural chromosome changes such as translocations, deletions, chromatid exchanges, and dicentrics were not different in the patient and the control groups. If the chromosome data reflect a general cancer risk, this risk cannot be considerably higher among the cancer-treated children.

Adolescent↗

Thyroid function in children after cytostatic treatment for acute leukemia.

Sixty-one children were examined for thyroid dysfunction as an adverse late effect after cessation of antileukemic treatment. The aim of the study was to contribute to clarifying which types of therapy can cause this endocrine disorder. Our treatment protocols do not include cranial irradiation as CNS prophylaxis, but we give relatively intensive intrathecal methotrexate treatment. The results indicate that this cytostatic regimen alone does not cause thyroid dysfunction as an adverse late effect.

Adolescent↗