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Biomedical subjects

H Schrøder

Publications and source records attributed to H Schrøder.

At least 19 recordsLinked to original sources
PubMed2006

Acute lymphoblastic leukemia in adolescents between 10 and 19 years of age in Denmark--secondary publication.

INTRODUCTION: Data seem to indicate that young adults with acute lymphoblastic leukemia (ALL) have a better survival when treated with pediatric protocols compared with adult ALL protocols. The purpose of the study was to report the clinical characteristics and outcome of all children and young adults 10-19 years of age diagnosed with ALL in Denmark between 1992 and 2001. MATERIAL: The study includes 99 patients 10-19 years of age with ALL in Denmark during a ten year period found in the complete NOPHO (Nordic Society of Pediatric Hematology and Oncology) registry and through the Danish Cancer Registry and local pathology databases. Data were retrieved by reviewing medical charts of the patients. A total of 61 children (10-14 years) treated on pediatric protocols and 38 young adults (15-19 years) were diagnosed with ALL. Data were reported as of January 1st 2005. RESULTS: There were no difference with respect to the distribution of T-ALL, CNS-leukemia, total white blood count and high risk chromosomal abnormalities between the two groups. There was a statistical significant lower event free survival (p<0.01) and lower overall survival (p<0.01) in young adults compared with 10-14 year-old children (0.38 vs 0.60 and 0.47 vs 0.67). There were more transplant-related deaths in the young adults. Higher treatment intensity in children may be an additional explanatory factor. Children received more prednisone, vincristine and high-dose methotrexate than young adults. CONCLUSION: Young adult patients with ALL might benefit from therapy with pediatric NOPHO ALL protocols.

Adolescent↗
PubMed2005

G(2) chromosomal radiosensitivity in Danish survivors of childhood and adolescent cancer and their offspring.

In order to investigate the relationship between chromosomal radiosensitivity and early-onset cancer, the G(2) chromosomal radiosensitivity assay was undertaken on a group of 23 Danish survivors of childhood and adolescent cancer, a control group comprising their partners and a group of 38 of their offspring. In addition, the previously reported in-house control group from Westlakes Research Institute (WRI) was extended to 27 individuals. When using the 90th percentile cutoff for the WRI control group, the proportion of individuals with elevated radiosensitivity was 11, 35, 52 and 53% for the WRI control, partner control, cancer survivor and the offspring groups, respectively, with significant differences between the WRI control group and the cancer survivor group (P=0.002) and the offspring group (P<0.001). However, while the comparisons with the WRI control group support an association of chromosomal radiosensitivity with cancer predisposition, when the partner control group was used to define the radiosensitivity cutoff point, no significant differences in radiosensitivity profiles were found between the partner control group and either the cancer survivor group or the offspring group. The failure to distinguish between the G(2) aberration profiles of the apparently normal group of partners and the cancer survivor group suggests that any association with cancer should be viewed with caution, but also raises questions as to the suitability of the partners of cancer survivors to act as an appropriate control group. Heritability of the radiosensitive phenotype was examined by segregation analysis of the Danish families and suggested that 67.3% of the phenotypic variance of G(2) chromosomal radiosensitivity is attributable to a putative major gene locus with dominant effect.

Adolescent↗
PubMed2001

Pharmacokinetics of Erwinia asparaginase after intravenous and intramuscular administration.

PURPOSE: To describe the pharmacokinetics of Erwinia asparaginase (ASNase) after intravenous (i.v.) and intramuscular (i.m.) administration. METHODS: A group of 29 children with newly diagnosed acute lymphoblastic leukemia (ALL) received Erwinia ASNase 30,000 IU/m2 every day for 10 days during multiagent induction therapy. Of these patients. 13 received i.v. therapy and 16 received i.m. therapy. During the reinduction phase the patients received Erwinia ASNase 30,000 IU/m2 twice a week for 2 weeks (Mondays and Thursdays) (8 patients in the i.v.-treated group and 11 patients in the i.m.-treated group). ASNase activity (spectrophotometric assay) was measured in plasma samples obtained from the patients at various times during therapy. RESULTS: The estimated half-life was 6.4 +/- 0.5 h (n = 13), the absorption rate after i.m. administration was found to limit elimination. The apparent volume of distribution corresponded well with the volume of plasma. The estimated clearance suggested that Erwinia ASNase is a low-clearance drug. Bioavailability after i.m. administration was (mean +/- SEM) 27.0 +/- 4.5% (range 11-61%; n = 12). CONCLUSIONS: In this study the pharmacokinetic parameters after i.v. and i.m. administration of Erwinia ASNase were determined based on a substantial number of patients. The present findings emphasize the importance of conducting proper pharmacokinetic studies before a new drug or a new preparation of a drug is introduced in a different schedule.

Adolescent↗
PubMed2001

Monitoring of Erwinia asparaginase therapy in childhood ALL in the Nordic countries.

AIMS: Evaluation of L-asparaginase therapy in the NOPHO-92 ALL-protocol (treatment protocol of acute lymphoblastic leukaemia of the Nordic Society of Paediatric Haematology and Oncology, initiated in 1992) after intravenous and intramuscular administration of Erwinia asparaginase during induction and re-induction therapy. METHODS: Forty children with newly diagnosed acute lymphoblastic leukaemia received Erwinia asparaginase (30 000 IU/m2 i.v. or i.m.) during induction therapy (every day for 10 days), and 19 children received Erwinia asparaginase (30 000 IU/m2 i.v. or i.m.) during re-induction therapy (twice a week for 2 weeks). Within the treatment periods asparaginase trough activity (using a spectrophotometric assay) was determined on specific days. The goal of therapy is complete L-asparagine depletion, which asparaginase activities above 100 IU l(-1) have been shown to ensure. Therefore determination of L-asparagine (using a h.p.l.c. method) was performed only in plasma samples with asparaginase activities below 100 IU l(-1). RESULTS: During induction therapy 92.2% of the trough enzyme activities were above 500 IU l(-1) for the i.v.-treated patients, and 92.4% of the trough enzyme activities were above 500 IU l(-1) for the i.m.-treated patients. During re-induction therapy 64.7% of the trough enzyme activities were below 100 IU l(-1) in the i.v.-treated group, and 73.3% of the trough enzyme activities were below 100 IU l(-1) in the i.m.-treated group. For trough enzyme activities below 100 IU l(-1) L-asparagine depletion was complete in two thirds of the samples. CONCLUSIONS: In the NOPHO-92 ALL-protocol L-asparaginase treatment during induction therapy was unnecessarily intense, but during the re-induction phase it appeared inadequate.

Adolescent↗
PubMed2001

Comparison of intramuscular therapy with Erwinia asparaginase and asparaginase Medac: pharmacokinetics, pharmacodynamics, formation of antibodies and influence on the coagulation system.

Asparaginase comes from different biological sources and the various preparations have different pharmacokinetic properties, and their tendency to induce side-effects is different. Erwinia asparaginase (ASNase) has a shorter half-life than the Escherichia coli preparations, and it has been reported to be less immunogenic than the E. coli preparations and to induce fewer coagulation disorders. Children with newly diagnosed acute lymphoblastic leukaemia (ALL) were included in this study. Twenty-seven patients were treated with Erwinia ASNase (induction therapy 30.000 IU/m2/d i.m. for 10 d, and re-induction therapy 30.000 IU/m2 twice a week for 2 weeks) and 15 were treated with ASNase Medac (induction therapy 1.000 IU/m2/d i.m. for 10 d, and re-induction therapy 5.000 IU/m2 i.m. twice a week for 2 weeks). Blood samples were drawn to determine enzyme activity, l-asparagine, anti-asparaginase antibodies, and coagulation parameters. After i.m. administration, Erwinia ASNase displayed a protracted absorption phase compared to ASNase Medac. The mean bioavailability after i.m. administration was 27% for Erwinia ASNase and 45% for ASNase Medac respectively. Mean trough enzyme activities during induction therapy were Erwinia ASNase 1748 IU/l and ASNase Medac 272 IU/l, and during re-induction therapy Erwinia ASNase 83 IU/l and ASNase Medac 147 IU/l. We conclude that in this setting, therapy with ASNase Medac resulted in sufficient treatment during both phases of therapy, whereas treatment with Erwinia ASNase resulted in unnecessarily intense therapy during the induction phase and insufficient treatment during the re-induction phase. There was no significant difference in the incidence of antibody formation, and therapy with Erwinia ASNase resulted in a more pronounced influence on the coagulation parameters than therapy with ASNase Medac.

Absorption↗
PubMed2001

Antibacterial prophylaxis with trimethoprim-sulfamethoxazole during induction treatment for acute lymphoblastic leukemia.

BACKGROUND AND PURPOSE: Children with acute lymphoblastic leukemia are treated with intensive chemotherapy resulting in profound immuno suppression. Therefore treatment with trimethoprim-sulfamethoxazole (TMP-SMX) may be used for prophylaxis against infections both with bacteria and Pneumocystis carinii in some departments. The use of TMP-SMX for prophylaxis during the induction therapy is not uniform in the four departments of pediatric oncology in Denmark. This gave us the opportunity to describe the effect of TMP/SMX on bacterial infections in children with ALL during the induction therapy. MATERIAL AND METHODS: Between January 1st 1992 and December 31st 1997, 210 children were diagnosed with ALL in Denmark. Based on a retrospective review of the medical charts the number of children with fever (>38 degrees C), the number of febrile days, days of antibiotic treatment and the number of positive blood cultures were registered for every febrile episode. RESULTS: One hundred and fourteen children received TMP/SMX prophylaxis (10-30 mg/SMX/kg/day) and 76 did not. Children who received TMP/SMX prophylaxis had significantly fewer episodes of fever (66/114 (58%) v 60/76 (79%), p <0,01), and significantly fewer children who received TMP/SMX prophylaxis had positive blood cultures before start of antibiotic treatment compared with children who did not receive prophylaxis (23/114 (20%) vs 37/76 (49%), p<0.001)). Nineteen different species were isolated from the blood stream before start of antibiotic treatment. In the non-prophylaxis group there was a preponderance of isolates with Staph. aureus, Str. pneumoniae, E. coli and P. aeruginosa. There was no difference in the mortality between the two groups (p=0.44). There were no cases of P carinii pneumonia in the period of induction therapy. CONCLUSION: TMP/SMX prophylaxis during induction therapy for childhood ALL seems to reduce the risk of bacteremias and febrile illness.

Anti-Bacterial Agents↗
PubMed1999

Possible carcinogenic effect of 6-mercaptopurine on bone marrow stem cells: relation to thiopurine metabolism.

BACKGROUND: 6-Mercaptopurine (6MP) has been regarded as nonleukemogenic, even though the cytotoxicity of 6MP depends on the incorporation of 6-thioguanine nucleotides (6TGN) into DNA. In hematopoietic cells this pathway competes with S-methylation catalyzed by thiopurine methyltransferase (TPMT). However, methylated 6MP metabolites inhibit purine de novo synthesis and thus may enhance incorporation of 6TGN into DNA. Approximately 10% of white individuals have low TPMT activity as a result of polymorphisms in the TPMT gene. The authors attempted to test the hypothesis that the degree of DNA damage during 6MP therapy might reflect variations in 6MP metabolism and pharmacokinetics. METHODS: The authors measured TPMT activity as well as erythrocyte levels of 6TGN (E-6TGN) and methylated 6MP metabolites (E-MeMP) during 6MP therapy in 439 children with acute lymphoblastic leukemia, 5 of whom later developed secondary myelodysplasia or acute myeloid leukemia (sMDS/AML). RESULTS: The patients who developed sMDS/AML had significantly lower TPMT activity compared with the remaining patients (P = 0.03). The 55 patients with TPMT activity <14 U/mL red blood cells (RBC) (antimode of the bimodal distribution) had a 5-year risk of sMDS/AML of 9 +/- 6% versus 1 +/- 1% for the remaining patients (P = 0.002). Cox regression analysis identified TPMT activity and E-MeMP level as the strongest predictors of risk for sMDS/AML (global P value = 0.02). Patients with low TPMT activity and high E-MeMP levels had the highest risk. All 5 patients with sMDS/AML had E-6TGN and/or E-MeMP levels > the 90% percentiles or had TPMT activity < 14 U/mL RBC. CONCLUSIONS: These data demonstrate an increased leukemogenic risk when 6MP is administered with other cytotoxic agents in patients with low TPMT activity, and indicate that not only high 6TGN levels but also high levels of methylated metabolites may lead to DNA damage.

Adolescent↗
PubMed1998

[Bacteremia in children with acute lymphoblastic leukemia].

The purpose of this study was to describe the pattern of bacterial infections in children with acute lymphoblastic leukemia. Forty-six children with ALL were treated for 119 febrile episodes. Antibiotic therapy was initiated with ampicillin and gentamicin, +/- dicloxacillin and lasted for 5-8 days. Bacterial cultures were positive in 36 of 119 febrile events. At the beginning of the febrile disease there was no difference in CRP and neutrophil count between children with positive and negative blood cultures. The maximum CRP was, however, significantly higher in children with positive blood cultures. In 75% there was no need to change the initial antibiotic treatment with ampicillin and gentamicin +/- dicloxacillin. If the temperature has been normal for 2-3 days and the neutrophil count is increasing it appears safe to discontinue the antibiotic therapy after five days when blood cultures are negative and after 7-8 days when cultures are positive.

Anti-Bacterial Agents↗
PubMed1996

Outcome for patients with leukemia, multiple myeloma and lymphoma who relapse after high dose therapy and autologous stem cell support.

Relapses after autologous transplantation are a serious clinical problem in patients with haematological diseases. The decision making for handling of such patients is difficult and the aim of this retrospective analysis of posttransplant relapses was 1) to obtain information of practical importance for the management of future relapses and 2) to evaluate the basis for clinical phase I-II trials of salvage therapy combined with biological modifiers. Included in the study were 283 patients with acute leukemia, multiple myeloma and malignant lymphoma who relapsed after autologous transplantations during a five year period from 1989 to 1994. Chemo- and radiotherapy was given to 229 patients after relapse or due to progressive disease and the response evaluated after 90 days. Fifty four patients (24%) obtained a complete remission and 44 patients (19%) partial responses. The overall median survival from relapse was 5 months. In the group given salvage treatment the median survival was 7 months and in the 54 patients who obtained remission the median survival was 15 months. So far 6 of 14 patients in continuous complete remission have a remission time after relapse longer than the time in remission after transplantation. Survival after relapse depended upon the time from transplantation to relapse, primary disease and if salvage therapy was given. In conclusion posttransplant relapses can be treated but the strategy has to be evaluated in future clinical trials.

Adolescent↗
PubMed1995

Risk of relapse in childhood acute lymphoblastic leukemia is related to RBC methotrexate and mercaptopurine metabolites during maintenance chemotherapy. Nordic Society for Pediatric Hematology and Oncology.

PURPOSE: During maintenance chemotherapy for childhood acute lymphoblastic leukemia (ALL), the cytotoxic metabolites of methotrexate (MTX polyglutamates) and mercaptopurine (6MP) (thioguanine nucleotides [6TGN]) accumulate intracellularly, including in erythrocytes (E-MTX and E-6TGN) with large interindividual variations. In the present Nordic Society for Pediatric Hematology and Oncology (NOPHO) study, the relation of E-MTX and E-6TGN to relapse risk was explored. PATIENTS AND METHODS: Two hundred ninety-seven patients with non-B-cell ALL, aged 1 to 14 years, on oral MTX and 6MP had E-MTX and E-6TGN levels measured three to 35 (median, eight) and three to 75 (median, nine) times, respectively. For each patient, a mean of all E-MTX (mE-MTX) and E-6TGN (mE-6TGN) measurements was calculated, as well as the product of mE-MTX and mE-6TGN (mE-MTX-6TGN), since MTX and 6MP may have synergistic action. RESULTS: For patients in remission, the median mE-MTX and mE-6TGN values were 4.7 nmol/mmol hemoglobin (Hgb) (range, 0.4 to 10.3) and 173 nmol/mmol Hgb (range, 58 to 846). With a median follow-up duration of 66 months for patients in remission, 64 patients relapsed. Cox regression analysis identified mE-MTX-6TGN and sex to be the most significant parameters to predict relapse (global P = .001). Factors that predicted a better prognosis were high mE-MTX 6TGN and female sex. Patients who had a mE-MTX-6TGN less than the product of the median mE-MTX and median mE-6TGN (813 [nmol/mmol Hgb]2) had a significantly poorer event-free survival (EFS) than did patients with higher values (5-year probability of EFS [pEFS5y], 0.70 v 0.86; P = .001). CONCLUSION: The pharmacokinetics of MTX and 6MP may have significant influence on the risk of relapse. The value of dose adjustments by E-MTX and E-6TGN remains to be determined.

Administration, Oral↗
PubMed1994

Methotrexate and 6-mercaptopurine maintenance therapy for childhood acute lymphoblastic leukemia: dose adjustments by white cell counts or by pharmacokinetic parameters?

In a consecutive study of 14 boys and 17 girls with non-B-cell ALL who were > or = 1 year of age at diagnosis, the degree of myelosuppression during the last year of MTX/6MP maintenance therapy was analyzed in relation to the erythrocyte concentration of MTX polyglutamates and 6-thioguanine nucleotides (E-MTX and E-6TGN, the respective major cytotoxic metabolites of MTX and 6MP). For each patient, E-MTX and E-6TGN levels were measured 2-15 (median, 6) and 2-17 (median, 7) times, respectively. From these measurements, arithmetic means of E-MTX and E-6TGN were calculated (mE-MTX and mE-6TGN, respectively). Since MTX and 6MP probably work synergistically, the product of mE-MTX and mE-6TGN was calculated for each patient (mE-MTX x 6TGN). The degree of myelosuppression was registered as the mean WBC determined following cessation of the therapy minus the mean WBC measured during the therapy (mWBCshift). The mean WBCs measured on therapy (mWBC(on)) and off therapy were highly correlated (r = 0.48, P = 0.009). The median mWBCshift was 2.7 x 10(9)/l (range, 1.4-4.8 x 10(9)/l). In a multivariate regression analysis, the best-fit model to predict the mWBCshift included mE-MTX x 6TGN, age at drug withdrawal, and mWBC in the order given [mWBCshift = 4.3 + 0.00089 x (mE-MTX x 6TGN) - 0.097 x age - 0.41 x mWBC(on); global rs = 0.66, P = 0.0002]. Thus, the patients with higher mE-MTX x 6TGN values, the younger patients, and the patients with the lowest WBC during therapy had the most pronounced degree of myelosuppression as measured by mWBCshift. These results indicate that E-MTX and E-6TGN may give a better reflection of the treatment intensity than do the WBCs alone.

Adolescent↗
PubMed1993

[Autologous bone marrow transplantation in children].

Autologous bone marrow transplantation is used for children with cancers which are only partially responsive to bone marrow toxic doses of cancer chemotherapy and irradiation. The use of megatherapy and autologous bone marrow transplantation instead of conventional doses for children has yielded substantial benefits in B-cell lymphoma, relapse of leukaemia, disseminated neuroblastoma and germ cell tumors. In the case of Wilms' tumor, rhabdomyosarcoma, osteosarcoma and Ewing's sarcoma with a partial initial response or a relapse, autologous bone marrow transplantation has been used to a limited extent. Based on the best results from conventional therapy and autologous bone marrow transplantation, respectively, the present need for autologous bone marrow transplantation in Denmark is estimated to be 24 transplantations a year.

Bone Marrow Transplantation↗
PubMed1993

[Autologous bone marrow transplantation in children with malignant diseases. Bone marrow harvest and procedure-related toxicity].

The aim of this paper was to present the results of bone marrow harvest followed by cryopreservation in 22 children with various malignant diseases, and the clinical course of autologous bone marrow transplantation (ABMT) performed in 10 children (three with acute lymphoblastic leukemia (ALL), three with acute myeloblastic leukemia (AML) and four neuroblastoma stage IV (NB)). In 20/22 children the harvested bone marrow contained a sufficient number of granulocyte-macrophage-colonyforming units (GM-CFU) for later marrow reinfusion. Hematological reconstitution was obtained in all 10 children who underwent ABMT. No child died of toxicity. The median time to neutrophil count > 0.5 x 10(9)/l, thrombocyte count > 50 x 10(9)/l and to discharge from hospital were 34, 49 and 29 days respectively. Five children are alive with no evidence of active disease 11-21 months after ABMT. Five children have suffered relapse and have died. It was concluded that sufficient amounts of precursor bone marrow cells may be harvested in children during a pause in cystostatic therapy. The acute toxicity of ABMT in children with malignant diseases was only moderate.

Adolescent↗
PubMed1993

Radiation-induced brachial plexopathy: neurological follow-up in 161 recurrence-free breast cancer patients.

PURPOSE: The purpose was to assess the incidence and clinical manifestations of radiation-induced brachial plexopathy in breast cancer patients, treated according to the Danish Breast Cancer Cooperative Group protocols. METHODS AND MATERIALS: One hundred and sixty-one recurrence-free breast cancer patients were examined for radiation-induced brachial plexopathy after a median follow-up period of 50 months (13-99 months). After total mastectomy and axillary node sampling, high-risk patients were randomized to adjuvant therapy. One hundred twenty-eight patients were treated with postoperative radiotherapy with 50 Gy in 25 daily fractions over 5 weeks. In addition, 82 of these patients received cytotoxic therapy (cyclophosphamide, methotrexate, and 5-fluorouracil) and 46 received tamoxifen. RESULTS: Five percent and 9% of the patients receiving radiotherapy had disabling and mild radiation-induced brachial plexopathy, respectively. Radiation-induced brachial plexopathy was more frequent in patients receiving cytotoxic therapy (p = 0.04) and in younger patients (p = 0.04). The clinical manifestations were paraesthesia (100%), hypaesthesia (74%), weakness (58%), decreased muscle stretch reflexes (47%), and pain (47%). CONCLUSION: The brachial plexus is more vulnerable to large fraction size. Fractions of 2 Gy or less are advisable. Cytotoxic therapy adds to the damaging effect of radiotherapy. Peripheral nerves in younger patients seems more vulnerable. Radiation-induced brachial plexopathy occurs mainly as diffuse damage to the brachial plexus.

Adult↗
PubMed1991

[Screening for neuroblastoma in infants aged 6 months. A method of testing].

In a number of cases, neuroblastoma (NB) may be diagnosed by routine screening of the urine for vanillinic-mandelic acid (VMA) and homovanillinic acid (HVA) in symptomfree infants at the age of six months. Early diagnosis of this disease may possibly improve the prognosis. The object of this project was to establish a method of measuring VMA and HVA concentrations in urine collected on filter paper and to assess participation by the parents as regards three different methods of collecting urine with the object of establishing a population screening programme for NB in Denmark. A total of 1,111 infants aged 6-8 months participated in the investigation. The equipment for testing the urine was given in three different was: 1) By the health nurses (County of Arhus), 2) By the general practitioner at the 6-month vaccination (County of Ringkøbing) and 3) By post (County of Viborg). In Arhus, the health nurses delivered the equipment to 96.7% of the age group concerned. Altogether, urine samples were obtained from 673 infants (61%). Participation was greatest in the County of Arhus (66%) and the County of Ringkøbing (62%) and lowest in the County of Viborg (54%). Two infants were found with marginally raised VMA or HVA but these values were found to be normal on repeated examinations. No cases of neuroblastoma were found in the material nor in the screened group in the course of 1 1/2 years after the conclusion of the investigation. In just over 3% of the cases, renewed urine samples had to be sent on account of too little urine on the filter paper. If current population investigations reveal that screening for neuroblastoma can alter the course of the disease in children, the method described here may form the basis for introduction of population investigations in Denmark.

Denmark↗