Publications by authors named "N M A Blijlevens"

197 Publications

Methodology of the DCCSS later fatigue study: a model to investigate chronic fatigue in long-term survivors of childhood cancer.

BMC Med Res Methodol 2021 May 16;21(1):106. Epub 2021 May 16.

Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.

Background: A debilitating late effect for childhood cancer survivors (CCS) is cancer-related fatigue (CRF). Little is known about the prevalence and risk factors of fatigue in this population. Here we describe the methodology of the Dutch Childhood Cancer Survivor Late Effect Study on fatigue (DCCSS LATER fatigue study). The aim of the DCCSS LATER fatigue study is to examine the prevalence of and factors associated with CRF, proposing a model which discerns predisposing, triggering, maintaining and moderating factors. Triggering factors are related to the cancer diagnosis and treatment during childhood and are thought to trigger fatigue symptoms. Maintaining factors are daily life- and psychosocial factors which may perpetuate fatigue once triggered. Moderating factors might influence the way fatigue symptoms express in individuals. Predisposing factors already existed before the diagnosis, such as genetic factors, and are thought to increase the vulnerability to develop fatigue. Methodology of the participant inclusion, data collection and planned analyses of the DCCSS LATER fatigue study are presented.

Results: Data of 1955 CCS and 455 siblings was collected. Analysis of the data is planned and we aim to start reporting the first results in 2022.

Conclusion: The DCCSS LATER fatigue study will provide information on the epidemiology of CRF and investigate the role of a broad range of associated factors in CCS. Insight in associated factors for fatigue in survivors experiencing severe and persistent fatigue may help identify individuals at risk for developing CRF and may aid in the development of interventions.
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http://dx.doi.org/10.1186/s12874-021-01298-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127233PMC
May 2021

A randomized controlled trial of manual versus powered tooth brushing during haematopoietic stem cell transplantation.

Oral Dis 2021 May 8. Epub 2021 May 8.

Department of Dentistry, Radboudumc, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.

Aim: To compare manual and powered tooth brushing (MT and PT) with respect to patient compliance to brushing frequency advice, plaque removal and severity of oral mucositis (OM) in patients undergoing hematopoietic stem cell transplantation (HSCT) after high-dose chemotherapy.

Materials & Methods: A randomized controlled trial was conducted. Forty-six patients scheduled to receive myeloablative conditioning regimen before autologous HSCT were included and randomly assigned to control (MT, n = 23) or test (PT, n = 23) groups. Starting at day 1 (day of hospital admission for HSCT), brushing frequency (patient recorded diary), plaque scores (Plaque Control Index) and oral mucositis (Oral Mucositis Nursing Index) were recorded daily. Data for days 1 to 17 were analysed using regression analysis and general linear models.

Results: Few patients maintained 4 times per day brushing, but most brushed at least 2 times per day throughout the study. In PT, overall plaque scores were lower by 6.98% (p = .006) as compared to MT. No differences were seen in OM scores between the groups (p = .968). A small but significant positive correlation was found between plaque scores and OM severity: R =0.15 (p < .01).

Conclusions: Powered tooth brushing resulted in lower plaque scores, but was not associated with reduced OM severity. Individual plaque scores were positively related to OM severity.
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http://dx.doi.org/10.1111/odi.13899DOI Listing
May 2021

A phase I clinical trial to study the safety of treatment with tipifarnib combined with bortezomib in patients with advanced stages of myelodysplastic syndrome and oligoblastic acute myeloid leukemia.

Leuk Res 2021 Jun 31;105:106573. Epub 2021 Mar 31.

Dept. of Hematology, Radboudumc, Nijmegen, the Netherlands; Dept. of Tumor Immunology, Radboudumc, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands.

Purpose: To determine the safety of tipifarnib in combination with escalating doses of bortezomib and to determine the maximum tolerated dose in patients with untreated high-risk MDS and oligoblastic acute myeloid leukemia, who were not eligible for intensive therapy.

Experimental Design: In a "3 + 3″ design, patients received fixed doses of tipifarnib 200 mg bid (days 1-21) and escalating doses of bortezomib (days 8, 15, 22) every 4 weeks in 4-6 cycles.

Results: The combination was tolerated well by the 11 patients in this study without reaching the maximum tolerated dose. Myelosuppression was the most frequent side effect, but usually of short duration. Interestingly a complete response with or without complete count recovery was observed in three patients and three additional patients had stable disease. The median duration of overall survival was 449 days. Two patients were still alive at 4.0 and 4.3 years, including one patient in continuing CR.

Conclusions: The combination of tipifarnib and bortezomib was tolerated well and appeared to have clinical activity in patients with high-risk MDS and AML with low counts of marrow blasts. Our results warrant further evaluation in a phase II study.
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http://dx.doi.org/10.1016/j.leukres.2021.106573DOI Listing
June 2021

Translational model of melphalan-induced gut toxicity reveals drug-host-microbe interactions that drive tissue injury and fever.

Cancer Chemother Pharmacol 2021 Apr 20. Epub 2021 Apr 20.

Department of Pediatrics (Molecular Metabolism and Nutrition), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Purpose: Conditioning therapy with high-dose melphalan (HDM) is associated with a high risk of gut toxicity, fever and infections in haematopoietic stem cell transplant (HSCT) recipients. However, validated preclinical models that adequately reflect clinical features of melphalan-induced toxicity are not available. We therefore aimed to develop a novel preclinical model of melphalan-induced toxicity that reflected well-defined clinical dynamics, as well as to identify targetable mechanisms that drive intestinal injury.

Methods: Male Wistar rats were treated with 4-8 mg/kg melphalan intravenously. The primary endpoint was plasma citrulline. Secondary endpoints included survival, weight loss, diarrhea, food/water intake, histopathology, body temperature, microbiota composition (16S sequencing) and bacterial translocation.

Results: Melphalan 5 mg/kg caused self-limiting intestinal injury, severe neutropenia and fever while impairing the microbial metabolome, prompting expansion of enteric pathogens. Intestinal inflammation was characterized by infiltration of polymorphic nuclear cells in the acute phases of mucosal injury, driving derangement of intestinal architecture. Ileal atrophy prevented bile acid reabsorption, exacerbating colonic injury via microbiota-dependent mechanisms.

Conclusion: We developed a novel translational model of melphalan-induced toxicity, which has excellent homology with the well-known clinical features of HDM transplantation. Application of this model will accelerate fundamental and translational study of melphalan-induced toxicity, with the clinical parallels of this model ensuring a greater likelihood of clinical success.
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http://dx.doi.org/10.1007/s00280-021-04273-7DOI Listing
April 2021

Low relapse risk in poor risk AML after conditioning with 10-day decitabine, fludarabine and 2 Gray TBI prior to allogeneic hematopoietic cell transplantation.

Bone Marrow Transplant 2021 Apr 6. Epub 2021 Apr 6.

Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Patients with poor risk acute myeloid leukemia (AML) have a dismal outcome. We hypothesized that combining decitabine with a standard non-myeloablative (NMA) conditioning regimen prior to allogeneic hematopoietic cell transplantation (allo HCT), might decrease the relapse incidence. We conducted a multicenter prospective phase II study (NCT02252107) with 10-day decitabine (20 mg/m/day) integrated in a standard non-myeloablative conditioning regimen (3 days fludarabine 30 mg/m with 2 Gray total body irradiation (TBI)). Patients with AML ≥ 18 years in 1st (in)complete remission (CR/CRi) with a poor or very poor risk profile, as defined by the HOVON-132 protocol, were eligible. Results: Forty-six patients (median age 60; range 23-74) were included. Median follow up time was 44 months (range 31-65 months). The cumulative 1-year incidence of relapse and NRM were respectively 23% and 11%. Incidence of grade III-IV acute graft-vs-host-disease (GVHD) and severe chronic GVHD were 13% and 20%, respectively. One-year OS was 70%. Application of ELN 2017 risk classification to the study cohort revealed a cumulative one-year relapse rate of respectively 31% and 13% for the adverse and intermediate risk patients. To conclude, the 10-day DEC/FLU/TBI conditioning regimen prior to allo HCT in poor risk AML patients is effective and feasible.
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http://dx.doi.org/10.1038/s41409-021-01272-3DOI Listing
April 2021