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45 results on '"Hählen, Karel"'

16. In vitro cytotoxicity of mitoxantrone, daunorubicin and doxorubicin in untreated childhood acute leukemia

Author

Kaspers, Gertjan J.L., Veerman, Anjo J.P., Pieters, Rob, Van Zantwijk, Ina, Klumper, Edwin, Hählen, Karel, De Waal, Frans C., Van Wering, Elisabeth R., Pediatric surgery, AII - Cancer immunology, CCA - Cancer biology and immunology, and CCA - Cancer Treatment and quality of life

Abstract

Mitoxantrone (MIT) has not been studied as a single agent in children with untreated leukemia. The antileukemic activity of MIT in these patients and its activity in relation to clinical and cell biological features is unknown. We studied the in vitro cytotoxicity of MIT, daunorubicin (DNR) and doxorubicin (DOX) in untreated childhood acute lymphoblastic leukemia (ALL, n=131) and acute nonlymphoblastic leukemia (ANLL, n=20) samples, using the MTT assay. There were marked interindividual differences in resistance to all three drugs. A strong, significant cross-resistance was found in ALL between MIT, DNR and DOX. ALL samples of the T-lineage, a prognostically unfavorable immunophenotype, however, were significantly more resistant to DNR and DOX, but not to MIT, than common or pre-B ALL samples. ALL cells from children with a prognostically unfavorable age at diagnosis, especially those < 2 years, showed a relative resistance to all three drugs compared to the intermediate age-group. This was found within all patients, but also within the common or pre-B ALL cases only. Sex, white blood cell count, or FAB type was not related to in vitro drug resistance. None of the three drugs showed an overall preferential activity in ALL or ANLL. We conclude that the in vitro antileukemic activity of MIT, DNR and DOX is related to certain clinical and cell biological features. There were no major differences between the three drugs in antileukemic activity, except that T-ALL samples were more resistant than common or pre-B ALL samples to DNR and DOX, while MIT was equally active in these two immunophenotypes.

Published
1994

17. Addition of PTK787/ZK 222584 can lower the dosage of amsacrine to achieve equal amounts of acute myeloid leukemia cell death

Author

Weidenaar, Alida C., primary, de Jonge, Hendrik J.M., additional, Fidler, Vaclav, additional, ter Elst, Arja, additional, Meeuwsen-de Boer, Tiny, additional, Douwes, Jenny, additional, Bouma-ter Steege, Jessica C.A., additional, Hählen, Karel, additional, Kamps, Willem A., additional, and de Bont, Eveline S.J.M., additional

Published
2008
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27. Circumvention of Methotrexate Resistance in Childhood Leukemia Subtypes by Rationally Designed Antifolates

Author

Rots, Marianne G., primary, Pieters, Rob, additional, Peters, Godefridus J., additional, van Zantwijk, Christina H., additional, Mauritz, Rob, additional, Noordhuis, Paul, additional, Willey, James C., additional, Hählen, Karel, additional, Creutzig, Ursula, additional, Janka-Schaub, Gritta, additional, Kaspers, Gertjan J.L., additional, Veerman, Anjo J.P., additional, and Jansen, Gerrit, additional

Published
1999
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39. Neuroblastoma 4S.

Author

Noesel, Max M. van, Hählen, Karel, Hakvoort-Cammel, Friederike G. A. J., and Egeler, R. Maarten

Published
1997
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40. Bone mineral density, body composition, and height in long-term survivors of acute lymphoblastic leukemia in childhood

Author

Sluis, Inge M. van der, Heuvel-Eibrink, Marry M. van den, Hählen, Karel, Krenning, Eric P., and Keizer-Schrama, Sabine M.P.F. de Muinck

Abstract

Childhood leukemia has increasing numbers of survivors, so more emphasis is being placed on long-term effects. The ALL-6 protocol of the Dutch Childhood Leukemia Study Group involved high-dose dexamethasone and methotrexate and no cranial irradiation. Therefore, we studied the long-term effects on bone mineral density (BMD), body composition, and growth in survivors of nonhigh-risk ALL treated with the ALL-6 protocol. Twenty-three subjects (12.2–25.4 years) participated in this cross-sectional study. Mean follow-up was 9.6 years (range 7.9–11.4 years). BMD of lumbar spine (LS) and total body (TB) and body composition were measured by dual energy X-ray absorptiometry; results are expressed as standard deviation scores (SDS). Bone mineral apparent density (BMADLS) was calculated to correct for bone size. A question-naire was administered to determine physical activity, calcium intake, and medical history. Mean SDS for BMDLS, BMDTB, and BMADLS were normal. None of the subjects had BMD below −2 SDS; one subject had BMADLS below −2 SDS. Mean SDS for lean body mass, percentage fat, and height were not significantly different from zero. Calcium intake correlated positively with BMD. Nine subjects reported traumatic fractures (eight during or shortly after therapy). Ten years after ALL-6 treatment, no long-term side effects on height, BMD, or body composition were found in this small group of patients, despite high-dose dexamethasone and methotrexate. This study suggests that ALL treatment without cranial irradiation might not be associated with long-term side effects on growth and BMD. Med. Pediatr. Oncol. 35:415–420, 2000. © 2000 Wiley-Liss, Inc.

Published
2000
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43. Outcome for children with relapsed acute myeloid leukemia in the Netherlands following initial treatment between 1980 and 1998: survival after chemotherapy only?

Author

Goemans BF, Tamminga RY, Corbijn CM, Hählen K, and Kaspers GJ

Subjects
Adolescent, Child, Child, Preschool, Female, Humans, Infant, Male, Netherlands epidemiology, Recurrence, Survival Rate, Time Factors, Treatment Outcome, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute epidemiology
Published
2008
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44. Protection against chemotherapy induced mucositis by TGF-beta(2) in childhood cancer patients: results from a randomized cross-over study.

Author

de Koning BA, Philipsen-Geerling B, Hoijer M, Hählen K, Büller HA, and Pieters R

Subjects
Adolescent, Antineoplastic Agents adverse effects, Child, Child, Preschool, Cross-Over Studies, Double-Blind Method, Female, Food, Gastrointestinal Diseases chemically induced, Gastrointestinal Diseases prevention & control, Humans, Infant, Male, Mouth Diseases chemically induced, Mouth Diseases prevention & control, Mouth Mucosa, Neoplasms drug therapy, Transforming Growth Factor beta2 blood, Mucositis chemically induced, Mucositis prevention & control, Transforming Growth Factor beta2 administration & dosage
Abstract

Background: Mucositis is one of the most frequent and severe side-effect of chemotherapy in childhood-cancer patients for which there is no prophylaxis available. The efficacy and feasibility of a TGF-beta(2)-enriched feeding for preventing oral and gastro-intestinal-mucositis in childhood-cancer patients were studied., Procedure: The study was designed as a two-period cross-over, randomized, double-blinded, placebo, controlled trial. Patients who had a high risk for developing mucositis and who would receive two comparable cycles of chemotherapy were eligible for the study. During one cycle of chemotherapy, TGF-beta(2)-enriched feeding was administered; during the other, a "placebo" (not enriched) feeding was used. WHO toxicity scales of diarrhea, oral mucositis, fever, anal lesions and nausea/vomiting were scored daily. In addition, the incidence of occurrence of blood cultures, antibiotic therapy, and interventions or diagnostics related to mucositis were measured., Results: The feasibility of the study was good: 83% of the patients completed two cycles and 86% of the study-feeding was effectively consumed. Administration of TGF-beta(2) was safe as serum TGF-beta(2) did not increase, and renal and liver function were not affected during TGF-beta(2) consumption compared to normal feeding. Differences in toxicity, scored during the whole observation period and the number of days with WHO 3/4 toxicity, were not significantly different between cycles with TGF-beta(2) enriched and normal feeding., Conclusions: TGF-beta(2) administration via feeding is well tolerated and safe. Although this study might have had limitations to show potential benefit of TGF-beta(2), it does not provide evidence that TGF-beta(2) decreases the incidence or degree of mucositis induced by combination chemotherapy in childhood-cancer patients.

Published
2007
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45. Vascular endothelial growth factor secretion is an independent prognostic factor for relapse-free survival in pediatric acute myeloid leukemia patients.

Author

de Bont ES, Fidler V, Meeuwsen T, Scherpen F, Hählen K, and Kamps WA

Subjects
Acute Disease, Adolescent, Age Factors, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Blood Cell Count, Child, Child, Preschool, Disease-Free Survival, Female, Humans, Infant, Infant, Newborn, Leukemia, Myeloid blood, Leukemia, Myeloid drug therapy, Leukemia, Myeloid metabolism, Leukemia, Myeloid mortality, Male, Prognosis, Risk Factors, Survival Analysis, Treatment Outcome, Tumor Cells, Cultured metabolism, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors, Endothelial Growth Factors metabolism, Intercellular Signaling Peptides and Proteins metabolism, Leukemia, Myeloid pathology, Lymphokines metabolism
Abstract

Substantial improvements in long-term survival have been made with acute myeloid leukemia (AML). However, the overall success rate in treatment of AML is around 50%, despite intensive chemotherapeutic regimens. AML cell survival seems to be related to vascular endothelial growth factor (VEGF). The purpose of this study was to investigate whether VEGF production by AML cells is a prognostic factor for therapeutic outcome and whether this is independent of known prognostic factors such as WBC count, French-American-British (FAB) classification, and risk assessment in which the presence of t(8;21), t(15;17), and inv(16) or FAB M3 defines a low-risk group. Pretreatment levels were measured in the supernatant of AML cells obtained from 47 children with newly diagnosed AML treated between 1988 and 1998. All patients were treated with intensive chemotherapeutic protocols from the Dutch Childhood Leukemia Study Group [DCLSG (DCLSG-ANLL87, DCLSG-ANLL92/94, and DCLSG-ANLL97)]. VEGF was measured at the mRNA level with reverse transcription-PCR and at the protein level using a VEGF immunoassay. VEGF in the supernatant from AML cells was highly variable and in concordance with reverse transcription-PCR results. The low-risk group had significantly lower VEGF levels compared with all others (P = 0.002). VEGF levels were significantly increased in AML FAB M4/M5 versus AML patients with FAB M1/M2/M3/M4eo (P = 0.011), who are reported to have a longer remission duration. Subsequently, the influence of different variables on therapeutic outcome was analyzed. No differences were found in overall survival. But within the limits of the small patient population, VEGF levels as well as age at diagnosis had an independent significant effect on relapse-free survival (P = 0.032 and P = 0.029, respectively) in multivariate analysis.

Published
2002

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