Publications by authors named "GertJan L Kaspers"

Renal function-based carboplatin dosing using measured glomerular filtration rate (GFR) results in more consistent drug exposure than anthropometric dosing. We aimed to validate the Newell dosing equation using estimated GFR (eGFR) and study which equation most accurately predicts carboplatin clearance in children with retinoblastoma. In 13 children with retinoblastoma 38 carboplatin clearance values were obtained from individual fits using MWPharm++.

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Background: Starting from 2014, the Indonesian government has implemented Universal Health Coverage (UHC) with the aim to make healthcare services accessible and affordable to all Indonesian citizens. A major reason for childhood cancer treatment failure in low- and middle-income countries, particularly among families with low socioeconomic status (SES), is abandonment of expensive cancer treatment. Our study compared childhood cancer treatment outcomes of the overall, low, and high SES population before and after introduction of UHC at a large Indonesian academic hospital.

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Study Question: Do genetic variations in the DNA damage response pathway modify the adverse effect of alkylating agents on ovarian function in female childhood cancer survivors (CCS)?

Summary Answer: Female CCS carrying a common BR serine/threonine kinase 1 (BRSK1) gene variant appear to be at 2.5-fold increased odds of reduced ovarian function after treatment with high doses of alkylating chemotherapy.

What Is Known Already: Female CCS show large inter-individual variability in the impact of DNA-damaging alkylating chemotherapy, given as treatment of childhood cancer, on adult ovarian function.

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Vincristine (VCR) is frequently used in pediatric oncology and can be administered intravenously through push injections or 1 h infusions. The effects of administration duration on population pharmacokinetics (PK) are unknown. We described PK differences related to administration duration and the relation between PK and VCR-induced peripheral neuropathy (VIPN).

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Limited data are available on the incidence and impact of TP53 alterations and TP53 pathway deregulation in paediatric acute myeloid leukaemia (AML). We analysed TP53 alterations in bone marrow samples of 229 patients with de novo paediatric AML, and detected heterozygous missense exon mutations in two patients (1%) and 17p deletions of the TP53 gene in four patients (2%). These patients more frequently had complex karyotype (50% vs.

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Data on occurrence, genetic characteristics and prognostic impact of complex and monosomal karyotype (CK/MK) in children with acute myeloid leukaemia (AML) are scarce. We studied CK and MK in a large unselected cohort of childhood AML patients diagnosed and treated according to Nordic Society for Paediatric Haematology and Oncology (NOPHO)-AML protocols 1993-2015. In total, 800 patients with de novo AML were included.

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Vincristine-induced peripheral neuropathy (VIPN) is a dose-limiting side effect of vincristine (VCR) treatment in children, leading to diminished quality of life. Much remains unknown about the underlying mechanisms of VIPN. This review systematically summarizes the available literature concerning contributing factors of VIPN development in children.

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Background: The cytogenetic aberrations inv(16)(p13.1q22)/t(16;16)(p13.1;q22), frequently detected in acute myelomonocytic leukemia with eosinophilia (FAB type M4eo), are generally considered a prognostically favorable subgroup.

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Introduction: Neuroblastoma (NBL) accounts for 10% of the paediatric malignancies and is responsible for 15% of the paediatric cancer-related deaths. Vanillylmandelic acid (VMA) and homovanillic acid (HVA) are most commonly analysed in urine of NBL patients. However, their diagnostic sensitivity is suboptimal (82%).

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Predictive tools for guiding therapy in children with brain tumors are urgently needed. In this first molecular drug imaging study in children, we investigated whether bevacizumab can reach tumors in children with diffuse intrinsic pontine glioma (DIPG) by measuring the tumor uptake of Zr-labeled bevacizumab by PET. In addition, we evaluated the safety of the procedure in children and determined the optimal time for imaging.

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Article Synopsis
  • PSMB5 mutations and increased β5 subunit expression in the proteasome are major factors in how leukemia cells develop resistance to the drug bortezomib (BTZ).
  • Research involving CCRF-CEM leukemia cells demonstrated that resistant subclones have decreased expression of stress-response genes and higher levels of the MARCKS gene, which is linked to a poor response to BTZ treatment.
  • The study indicates that MARCKS may facilitate the excretion of ubiquitinated proteins, helping resistant cells alleviate stress from proteasome inhibition, thus providing new insights into BTZ resistance mechanisms.
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We evaluated the in vitro glucocorticoid (GC) responsiveness of 117 pediatric acute myeloid leukemia cells by considering GC resistance, GC-induced proliferation, and GC-induced differentiation. None of the samples was highly GC sensitive, and only 15% were intermediately sensitive. GC-induced differentiation was not observed, while GC-induced proliferation was observed in 27% of the samples.

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Background: Retinoblastoma is a pediatric eye cancer associated with RB1 loss or MYCN amplification (RB1 (+/+) MYCN(A) ). There are controversies concerning the existence of molecular subtypes within RB1(-/-) retinoblastoma. To test whether these molecular subtypes exist, we performed molecular profiling.

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Pediatric acute lymphoblastic leukemia (ALL) is treated with combination chemotherapy including mercaptopurine (6MP) as an important component. Upon its uptake, 6MP undergoes a complex metabolism involving many enzymes and active products. The prognostic value of all the factors engaged in this pathway still remains unclear.

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The prognostic significance of early response to treatment has not been reported in relapsed pediatric acute myeloid leukemia. In order to identify an early and easily applicable prognostic factor allowing subsequent treatment modifications, we assessed leukemic blast counts in the bone marrow by morphology on days 15 and 28 after first reinduction in 338 patients of the international Relapsed-AML2001/01 trial. Both day 15 and day 28 status was classified as good (≤20% leukemic blasts) in 77% of patients.

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We describe a male child with multifocal kaposiform hemangioendothelioma in the right and left cervical region with development of Kasabach-Merritt syndrome. Treatment with interferon-alpha resulted in a good but only temporary clinical response.He relapsed 3 times with regrowth of the right cervical tumor.

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Three patients with stage 4S neuroblastoma without MYC-N amplification who progressed to stage 4 with persistent liver involvement, were treated with iodine 131-meta-iodobenzylguanidine therapy, chemotherapy, and surgery. Successive histologic examination of the liver showed differentiation of the tumor in 2 patients and fibrosis in the third. One patient died of brain metastases at the age of 30 months.

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The proteasome inhibitor bortezomib is a novel anticancer drug that has shown promise in the treatment of refractory multiple myeloma. However, its clinical efficacy has been hampered by the emergence of drug-resistance phenomena, the molecular basis of which remains elusive. Toward this end, we here developed high levels (45- to 129-fold) of acquired resistance to bortezomib in human myelomonocytic THP1 cells by exposure to stepwise increasing (2.

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Individuals with Down syndrome (DS) are predisposed to develop acute megakaryoblastic leukemia (AMKL), characterized by expression of truncated GATA1 transcription factor protein (GATA1s) due to somatic mutation. The treatment outcome for DS-AMKL is more favorable than for AMKL in non-DS patients. To gain insight into gene expression differences in AMKL, we compared 24 DS and 39 non-DS AMKL samples.

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Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant condition due to heterozygous germline mutations in DNA mismatch repair genes, in particular MLH1, MSH2 and MSH6. Recently, a syndrome was recognized in which children develop haematological malignancies, solid tumours and signs of neurofibromatosis type 1 due to bi-allelic MMR gene mutations in MLH1, MSH2 and PMS2. Here we describe the child of healthy consanguineous parents who had café-au-lait spots, oligodendroglioma, and rectal cancer.

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In order to assess the effect of the DNA polymerase inhibitor aphidicolin on resistance to cytosine arabinoside, blast cells from 15 children with ALL and 9 with AML were exposed to a range of concentrations of ara-C +/- aphidicolin. Cell survival was measured using the MTT assay. Aphidicolin significantly increased sensitivity to ara-C in blast cells from both ALL (p=0.

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