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Articles by M. M van den Heuvel Eibrink
Total Records ( 2 ) for M. M van den Heuvel Eibrink
  I. H. I. M Hollink , M. M van den Heuvel Eibrink , M Zimmermann , B. V Balgobind , S. T. C. J. M Arentsen Peters , M Alders , A Willasch , G. J. L Kaspers , J Trka , A Baruchel , S. S. N de Graaf , U Creutzig , R Pieters , D Reinhardt and C. M. Zwaan

Wilms tumor 1 (WT1) mutations have recently been identified in approximately 10% of adult acute myeloid leukemia (AML) with normal cytogenetics (CN-AML) and are associated with poor outcome. Using array-based comparative genome hybridization in pediatric CN-AML samples, we detected a WT1 deletion in one sample. The other WT1 allele was mutated. This prompted us to further investigate the role of WT1 aberrations in childhood AML. Mutations were found in 35 of 298 (12%) diagnostic pediatric AML samples. In 19 of 35 (54%) samples, more than one WT1 aberration was found: 15 samples had 2 different mutations, 2 had a homozygous mutation, and 2 had a mutation plus a WT1 deletion. WT1 mutations clustered significantly in the CN-AML subgroup (22%; P < .001) and were associated with FLT3/ITD (43 vs 17%; P < .001). WT1 mutations conferred an independent poor prognostic significance (WT1 mutated vs wild-type patients: 5-year probability of overall survival [pOS] 35% vs 66%, P = .002; probability of event-free survival 22% vs 46%, P < .001; and cumulative incidence of relapse or regression 70% vs 44%, P < .001). Patients with both a WT1 mutation and a FLT3/ITD had a dismal prognosis (5-year pOS 21%). WT1 mutations occur at a significant rate in childhood AML and are a novel independent poor prognostic marker.

  R. D van Beek , M. M van den Heuvel Eibrink , F. G Hakvoort Cammel , C van den Bos , H. J. H van der Pal , E. P Krenning , Y. B de Rijke , R Pieters and S. M. P. F. de Muinck Keizer Schrama

Background: The aim of this study was to investigate the long-term side effects of treatment for childhood Hodgkin’s lymphoma with chemotherapy only on growth, bone mineral density (BMD), body composition, and thyroid function.

Procedure: A total of 88 patients (56 male, 32 female; 17.6–42.6 yr), treated for childhood Hodgkin’s lymphoma from 1974–1998 with combination chemotherapy adriamycin (doxorubicin), bleomycin, vinblastine, and dacarbazine or epirubicin, bleomycin, vinblastine, dacarbazine with or without mechlorethamine, oncovin (vincristine), procarbazine, and prednisone (MOPP) with the intention to avoid radiotherapy, participated in this study. Median follow-up was 15.5 yr (range 5.6–30.2). BMD of lumbar spine and total body (BMD-TB), and body composition were measured using dual-energy x-ray absorptiometry. Bone mineral apparent density of the lumbar spine was calculated to correct for bone size. Free T4 and TSH were measured.

Results: Men treated with MOPP had a significantly reduced height with normal body proportions. Women treated with MOPP had decreased BMD-TB and bone mineral apparent density of the lumbar spine as compared with healthy controls. Percent body fat was significantly increased in female patients treated without MOPP. Body mass index was significantly increased in male patients treated without MOPP, whereas lean body mass was normal in all patients. All patients, except one, treated with chemotherapy only had normal thyroid function. However, five patients who received additional radiation to the thyroid either had abnormal levels of TSH or free T4, or used thyroid hormones.

Conclusions: Lean body mass was normal in all patients; thyroid function was normal in all but one patient. The use of MOPP leads to decreased height and increased body mass index in men and decreased BMD-TB in women.

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