J P Donnelly

Publications (91)357.28 Total impact

• Source

  Available from: Jacques Meis

  Dataset: CID1995 reply to Schaffner Pahls antagonism

  J F Meis, J P Donnelly, J A Hoogkamp-Korstanje, B E De Pauw
• Article: Lymphocyte subsets, granulocyte-colony-stimulating factor responsiveness and post-stem cell transplantation infections: mucositis is the underestimated confounder?

  W J F M van der Velden, J P Donnelly, N M A Blijlevens
  Cytotherapy 03/2012; 14(3):381-3. · 3.63 Impact Factor
• Article: How prompt is prompt in daily practice? Earlier initiation of empirical antibacterial therapy for the febrile neutropenic patient.

  M van Vliet, C M J Potting, P D J Sturm, J P Donnelly, N M A Blijlevens
  [show abstract] [hide abstract]
  ABSTRACT: With fever being the most common manifestation of early sepsis, clinical practice guidelines emphasise the prompt institution of broad-spectrum antibacterial therapy at its onset. An audit was performed on the haematology ward to determine whether there was any delay in starting antibiotic treatment during neutropenia in clinical patients and to define the main reasons for this. Strategies were developed, implemented and evaluated on short- and long-term implications on the delay in the start of antibacterial therapy. The procedures specified in the protocol for starting empirical antibacterial therapy were audited to assess whether the target for starting therapy within 30 min of fever was achieved. Initial results indicated that two major changes to the protocol were necessary to achieve a reduction in the delay between detection of fever and starting antibacterial therapy. This modified protocol was evaluated 4 months after implementation by means of a consecutive audit. After 3 years, a third audit was performed to determine the long-term implications of the improved protocol. In the initial audit, the mean time interval between the onset of fever and the administration of antibacterial therapy was 75 min. With the modified protocol, the mean time to starting therapy was shortened to 32 min (P < 0.05). Changing the protocol for starting antibacterial therapy allowed nurses to administer the first dose of antibiotic significantly earlier.
  European Journal of Cancer Care 09/2011; 20(5):679-85. · 1.17 Impact Factor
• Source

  Available from: Jacques Meis

  Article: European expert opinion on the management of invasive candidiasis in adults.

  B J Kullberg, P E Verweij, M Akova, M C Arendrup, J Bille, T Calandra, M Cuenca-Estrella, R Herbrecht, F Jacobs, M Kalin, [......], B E De Pauw, J H Rex, E Roilides, T R Rogers, M Ruhnke, A J Ullmann, Ö Uzun, K Vandewoude, J-L Vincent, J P Donnelly
  [show abstract] [hide abstract]
  ABSTRACT: This report discusses the present status of antifungal therapy and treatment options for candidaemia, considered by experts in the field in Europe. A conference of 26 experts from 13 European countries was held to discuss strategies for the treatment and prevention of invasive candidiasis, with the aim of providing a review on optimal management strategies. Published and unpublished comparative trials on antifungal therapy were analysed and discussed. Commonly asked questions about the management of candidaemia were selected, and possible responses to these questions were discussed. Panellists were then asked to respond to each question by using a touchpad answering system. After the initial conference, the viewpoint document has been reviewed and edited to include new insights and developments since the initial meeting. For many situations, consensus on treatment could not be reached, and the responses indicate that treatment is likely to be modified on a patient-to-patient basis, depending on factors such as degree of illness, prior exposure to azole antifungals, and the presence of potentially antifungal drug-resistant Candida species.
  Clinical Microbiology and Infection 09/2011; 17 Suppl 5:1-12. · 4.54 Impact Factor
• Article: Issues in genetic association studies: limitations of statistical analysis and biological plausibility.

  W J F M Van der Velden, T Feuth, W B C Stevens, J P Donnelly, N M A Blijlevens
  Bone marrow transplantation 06/2011; 46(6):906-7. · 3.00 Impact Factor
• Article: Differences in T cell depletion and intestinal mucositis explain inconsistent effects of NOD2/CARD15 polymophisms in SCT.

  W J F M van der Velden, J P Donnelly, N M A Blijlevens
  Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 04/2011; 17(10):1421-3. · 3.15 Impact Factor
• Article: Citrulline-based assessment score: first choice for measuring and monitoring intestinal failure after high-dose chemotherapy.

  A H Herbers, T Feuth, J P Donnelly, N M Blijlevens
  [show abstract] [hide abstract]
  ABSTRACT: Currently, objective tests are lacking that enable the extent and duration of intestinal mucosal damage induced by myeloablative chemotherapy to be determined. To address this problem, we explored a citrulline-based assessment score as this amino acid is a simple quantitative marker of intestinal failure. From March 2004 to June 2007, citrulline concentrations were determined at baseline and at least once weekly after the start of myeloablative chemotherapy until 30 days thereafter among 94 allogeneic or autologous haematopoietic stem-cell transplant recipients. The patients were divided into three groups according to the regimen they received: (i) carmustine, etoposide, cytarabine and melphalan/high-dose melphalan, (ii) cyclophosphamide and total body irradiation +/- antithymocyte globulin and (iii) idarubicin-containing regimens. Intestinal mucosal damage was described either by level of citrulline on each day, on the basis of different thresholds of citrulline indicating the severity of villous atrophy, or by area under the curve using reciprocal value of 10/citrulline. Regimens that incorporated idarubicin induced the most severe intestinal toxicity. Scores based on the level of citrulline, using severity thresholds, and on the area under the reciprocal curve are able to discriminate between the damage induced by different high-dose chemotherapy regimens. A citrulline-based assessment score appears objective, validated, reproducible, reliable, specific and sensitive making it a suitable first choice for measuring and monitoring intestinal mucositis.
  Annals of Oncology 08/2010; 21(8):1706-11. · 6.43 Impact Factor
• Article: NOD2 polymorphisms predict severe acute graft-versus-host and treatment-related mortality in T-cell-depleted haematopoietic stem cell transplantation.

  W J F M van der Velden, N M A Blijlevens, F M H M Maas, N P M Schaap, J H Jansen, B A van der Reijden, T Feuth, H Dolstra, J P Donnelly
  [show abstract] [hide abstract]
  ABSTRACT: Single nucleotide polymorphisms (SNPs) in the NOD2 gene have significant impact on both treatment-related mortality (TRM) and acute GVHD (aGVHD) in haematopoietic stem cell transplantation (HSCT). The effect of these polymorphisms when using T-cell-depleted grafts has been poorly studied. We retrospectively analysed NOD2 polymorphisms in a cohort of 85 patients and donors who received an HLA-identical sibling partially T-cell-depleted HSCT (0.5 x 10(6) CD3+ T cells per kg) following idarubicin-containing conditioning regimens. NOD2 polymorphisms were present in 14 of 85 (16.5%) of patients and 18 of 85 (21%) of donors. The risk of severe aGVHD (grade III-IV) and the 1-year TRM was significantly higher in the presence of NOD2 polymorphisms (hazard ratio (HR) 6.0, P=0.02 for severe aGVHD and HR 3.3, P=0.02 for TRM, respectively) and was most prominent in cases where patient and donor both had a polymorphism (HR 10.5, P=0.002 and HR 3.9, P=0.002). There was also a trend towards increased risk of bacteraemia due to coagulase-negative staphylococci in patients with an NOD2 polymorphism. We conclude that NOD2 polymorphism screening should be used to optimize donor selection and antimicrobial prophylaxis to reduce the occurrence of aGVHD and TRM following allogeneic HSCT.
  Bone marrow transplantation 03/2009; 44(4):243-8. · 3.00 Impact Factor
• Article: Circulating Candida-specific anti-mannan antibodies precede invasive candidiasis in patients undergoing myelo-ablative chemotherapy.

  F M Verduyn Lunel, J P Donnelly, H A L van der Lee, N M A Blijlevens, P E Verweij
  [show abstract] [hide abstract]
  ABSTRACT: The kinetics of circulating Candida mannan and anti-mannan antibodies were studied in consecutive plasma samples, obtained upon hospital admission, of 21 patients with microbiologically proven invasive candidiasis and 30 control patients who underwent myelo-ablative chemotherapy. The detection of Candida anti-mannan antibodies preceded the diagnosis of invasive candidiasis in infected patients, and the antibodies were detected significantly more often in patients who had experienced multiple episodes of neutropenia than in the control group (OR 8.9, 95% CI 5.6-14.3; p <0.05). Mannan was predominantly detected in patients who developed invasive candidiasis during their first episode of neutropenia (OR 3.7, 95% CI 1.4-9.7; p <0.05). This observation suggests that patients with multiple episodes of neutropenia have been previously exposed to Candida and that the presence of anti-mannan antibodies in these patients might be associated with an increased risk of developing clinically manifest invasive candidiasis.
  Clinical Microbiology and Infection 01/2009; 15(4):380-6. · 4.54 Impact Factor
• Source

  Available from: Walter J F M van der Velden

  Article: Febrile mucositis in haematopoietic SCT recipients.

  W J F M van der Velden, N M A Blijlevens, T Feuth, J P Donnelly
  [show abstract] [hide abstract]
  ABSTRACT: We undertook a retrospective analysis of a cohort of 67 patients with multiple myeloma who had received an autologous haematopoietic SCT (HSCT) following high-dose melphalan to explore the impact of mucositis on the systemic inflammatory response. A homogenous group of 16 patients without a documented infection and a group of 30 patients with bacteraemia were identified for whom complete data on neutropenia, an inflammatory response, infectious complications and mucositis were available. All patients showed a similar course of events with an inflammatory response coinciding with the occurrence of significant mucositis, regardless of the presence or absence of infection. The only differences between the two groups were significantly higher maximum C-reactive protein (CRP) levels and lower citrulline levels for patients with bacteraemia, suggesting a causative role for mucositis in the occurrence of bacteraemia. Statistical analysis showed a significant association over time between citrulline levels, to a lesser extent bacteraemia, but not neutropenia, and the inflammatory response measured by CRP. These data suggest that the inflammatory response after conditioning for a HSCT is the result of the chemotherapy-induced mucositis and independent of neutropenia. Though primary inflammation appeared due to mucositis, infections resulting from mucosal barrier injury and neutropenia aggravated the inflammatory response.
  Bone marrow transplantation 10/2008; 43(1):55-60. · 3.00 Impact Factor
• Article: Loss of enterocyte mass is accompanied by diminished turnover of enterocytes after myeloablative therapy in haematopoietic stem-cell transplant recipients.

  J P M Derikx, N M A Blijlevens, J P Donnelly, H Fujii, T Kanda, A A van Bijnen, E Heineman, W A Buurman
  [show abstract] [hide abstract]
  ABSTRACT: Intestinal mucosal barrier injury (MBI), resulting from myeloablative conditioning for haematopoietic stem-cell transplantation (HSCT), is an important cause of morbidity. Despite its frequency, recognition presents a challenge, while the aetiology needs still to be unravelled. The relationship between enterocyte mass and enterocyte loss was explored by examining citrulline serum levels and by assessing circulating intestinal fatty acid-binding protein (I-FABP) and ileal bile acid-binding protein (I-BABP), proteins released by dying mature enterocytes. Thirty-four adult patients with haematological malignancy received allogeneic HSCT (HSCT day 0) 12 days after being given idarubicin, cyclophosphamide and total body irradiation as myeloablative conditioning, a regimen known to induce oral and intestinal MBI. Serum levels of citrulline, I-FABP and I-BABP were measured on HSCT days -12, -6, 0, +7, +14 and +21. Myeloablative conditioning resulted in a significant decrease in serum citrulline with the nadir on HSCT day +7; thereafter, levels rose gradually. Simultaneously, a significant decrease in I-FABP and I-BABP levels occurred from the day of transplant until day +14. Simultaneous reduction and subsequent increase of citrulline and I-FABP and I-BABP levels following cytotoxic treatment show that enterocyte mass corresponds to lower rate of dying enterocytes, indicating reduced turnover of enterocytes. Assessment of enterocyte turnover and mass offers opportunities for evaluation of new MBI therapies.
  Annals of Oncology 09/2008; 20(2):337-42. · 6.43 Impact Factor
• Article: Bacteraemia coincides with low citrulline concentrations after high-dose melphalan in autologous HSCT recipients.

  A H E Herbers, N M A Blijlevens, J P Donnelly, T J M de Witte
  [show abstract] [hide abstract]
  ABSTRACT: Mucosal damage to the intestines induced by myeloablative conditioning for allogeneic PBSC transplant (PBSCT) can be determined by the concentration of citrulline, which is a functional marker of small intestinal enterocytes. Low citrulline concentrations in blood coincide with and are a response to severe mucosal barrier injury. We treated 29 patients with high-dose melphalan 200 mg/m(2) (Mel-200) to prepare for an autologous PBSCT and collected plasma samples from each patient starting before the myeloablative regimen and three times per week thereafter until discharge. The baseline citrulline concentration was 27.6 mM+/-4.0 (mean+/-95% confidence interval; CI), and citrulline concentrations declined rapidly thereafter reaching a nadir averaging 6.7 mM+/-2.7, 12 days after starting Mel-200. Citrulline concentrations, only increased gradually and were still low (12 mM+/-4) at discharge. A total of 20 patients developed fever, which was associated with bacteraemia in 10 cases. Their mean citrulline concentrations were lower at 5.5 mM+/-1.5 than were those of patients without bacteraemia (10.2 mM+/-3.9). Importantly, neither the number of preceding neutropenic days nor the mean C-reactive protein (CRP) concentration at the onset of fever was different between these two groups. In conclusion, citrulline concentrations rapidly decline after Mel-200 reflecting intestinal mucosal barrier injury. Low citrulline, rather than the duration of neutropenia, is associated with bacteraemia indicating the importance of an intact mucosal barrier in neutropenic patients.
  Bone Marrow Transplantation 07/2008; 42(5):345-9. · 3.75 Impact Factor
• Article: The potential role of lactoferrin and derivatives in the management of infectious and inflammatory complications of hematology patients receiving a hematopoietic stem cell transplantation.

  W J F M van der Velden, N M A Blijlevens, J P Donnelly
  [show abstract] [hide abstract]
  ABSTRACT: Human lactoferrin is a natural defense protein belonging to the innate immune system present in several body fluids and secretions, as well as in the secondary granules of polymorphonuclear neutrophils. Lactoferrin and its derivatives have pleiotropic functions including broad-spectrum anti-microbial activity, anti-tumor activity, regulation of cell growth and differentiation, and modulation of inflammatory as well as humoral and cellular immune responses. This is the reason why much research has addressed the potential therapeutic activity of these molecules in different clinical settings, especially regarding infectious diseases and uncontrolled inflammatory conditions. In patients with hematological malignancies treated with a hematopoietic stem cell transplantation (HSCT), morbidity and mortality due to infections and uncontrolled inflammation remains high, despite many advances in supportive care. These life-threatening complications are a result of the damage caused by the conditioning regimens to the mucosal barrier, and the innate and adaptive, humoral, and cellular immune defenses. These complications necessitate the continued exploration of new treatment modalities. Systemic and probably local levels of lactoferrin are decreased following HSCT. Therefore, the use of lactoferrin, or short peptide derivatives that retain the cationic N-terminal moiety that is essential for the anti-microbial and anti-inflammatory activity, may prove to be a promising versatile class of agents for managing the complications that arise from HSCT.
  Transplant Infectious Disease 05/2008; 10(2):80-9. · 2.22 Impact Factor
• Article: [Invasive zygomycosis in patients treated for haematological malignancies].

  P E Verweij, W J F M van der Velden, J P Donnelly, N M A Blijlevens, A Warris
  [show abstract] [hide abstract]
  ABSTRACT: A 52-year-old man underwent haematopoietic stem-cell transplant for myelodysplastic syndrome; after treatment with voriconazole for invasive aspergillosis, he was diagnosed with invasive zygomycosis caused by Rhizopus microsporus. He died despite treatment with intravenous liposomal amphotericin B and posaconazole. A 5-year-old boy with acute lymphatic leukaemia was diagnosed with invasive zygomycosis at autopsy. In a third case, a 16-year-old boy with acute myeloid leukaemia received repeated courses of empiric antifungal therapy, although the presence of an invasive fungal infection was not demonstrated. The patient died, and disseminated invasive zygomycosis caused by Rhizomucor pusillus was found at autopsy. Invasive infections by Zygomycetes are difficult to diagnose and are associated with a high mortality rate. The incidence of invasive zygomycosis appears to be increasing. Therefore, awareness of this type of invasive fungal infection is warranted. Lipid formulations ofamphotericin B remain the first choice for therapy.
  Nederlands tijdschrift voor geneeskunde 12/2007; 151(47):2597-602.
• Article: Determining mucosal barrier injury to the oesophagus using CT scan.

  N M A Blijlevens, J P Donnelly, D Yakar, C E van Die, T de Witte
  [show abstract] [hide abstract]
  ABSTRACT: Oral mucositis is recognised as one of the most debilitating complications of high-dose cytostatic chemotherapy used to prepare for haematopoietic stem cell transplantation (HSCT), but very little is known about oesophageal mucositis, as endoscopy is not routinely performed. We incorporate the computed tomography (CT) scan in the diagnostic workup of fever during neutropenia to detect evidence of pulmonary complications. This allowed us to evaluate whether mucosal barrier injury to the oesophagus can be determined. We selected 46 patients without oesophageal cancer or immune suppression (controls), who had a normal oesophagus, and measured the mucosal thickness at the upper part (UP), middle part (MP) and lower part (LP) of the oesophagus. Next, we selected 30 patients having a CT scan done for diagnostic purposes within 14 days after HSCT and measured mucosal thickness at the same levels. We also scored oral mucositis and gut toxicity. The mucosal thickness of the UP, MP and LP, respectively, for the controls (mean +/- SD) was 4.1 mm (+/-1.1), 4.2 mm (+/-1.2) and 4.8 mm (+/-1.3), and the corresponding values for the subjects were 5.9 mm (+/-2.2), 5.9 mm (+/-2.0) and 7.7 mm (+/-3.0). Analysis of variance showed statistically significant differences between subjects and controls at all oesophageal levels. All patients suffered from severe oral mucositis at the time. Hence, mucosal barrier injury to the oesophagus can be objectively measured using CT scan.
  Supportive Care Cancer 10/2007; 15(9):1105-8. · 2.60 Impact Factor
• Article: Cyclosporine short infusion and C2 monitoring in haematopoietic stem cell transplant recipients.

  M P Hendriks, N M A Blijlevens, A V M B Schattenberg, D M Burger, J P Donnelly
  [show abstract] [hide abstract]
  ABSTRACT: Blood concentrations of cyclosporine A (CsA) >or=800 microg/l measured 2 h post-dosing, the C2 concentration, is necessary to obtain a maximal pharmacological effect and correlates well with transplant-related complications such as transplant rejection and toxicity. In an open crossover study CsA blood levels were measured during 24 h to generate a pharmacokinetic profile on days 1, 8 and 15 after starting CsA infusion in 21 haematopoietic allogeneic stem cell transplant recipients who were receiving intravenously CsA 3 mg/kg/day either by continuous infusion or by 2 h infusion given every 12 h. C2 levels after the 2 h infusion correlated better than C1 or C3 levels with the area under the concentration-time curve from 0 to 4 h (r2=0.62). C2 levels >or=800 microg/l were also achieved for 20 out of 24 (83%) of cases after the 2 h infusion of CsA without any increase of CsA-related toxicity but for only three of the 23 patients (13%) after continuous infusion. Therefore, we recommend CsA infusions in 2 h during transplant and perform C2 monitoring to obtain therapeutic C2 levels >or=800 microg/l.
  Bone Marrow Transplantation 11/2006; 38(7):521-5. · 3.75 Impact Factor
• Article: Primary hepatic invasive aspergillosis with progression after rituximab therapy for a post transplantation lymphoproliferative disorder.

  W J F M van der Velden, N M A Blijlevens, R R Klont, J P Donnelly, P E Verweij
  [show abstract] [hide abstract]
  ABSTRACT: We present a case of primary hepatic and possible splenic invasive aspergillosis (IA), which progressed under anti-CD20 B cell treatment for posttransplantation lymphoproliferative disease following allogeneic stem cell transplantation, to highlight the clinical value of a positive galactomannan-antigen test, an intestinal portal of entry of Aspergillus, and the detrimental effect of B lymphocyte depletion in IA.
  Annals of Hematology 10/2006; 85(9):621-3. · 2.62 Impact Factor
• Article: A scoring system for the assessment of oral mucositis in daily nursing practice.

  C M J Potting, N A M Blijlevens, J P Donnelly, T Feuth, T Van Achterberg
  [show abstract] [hide abstract]
  ABSTRACT: Nurses take care of patients around the clock, so they are in an ideal position to observe and record the signs and symptoms of oral mucositis. This requires a valid, reliable scoring instrument that is easy to use. The objectives of this study were to summarize the scoring instruments that are available, to develop a new Nijmegen Nursing Mucositis Scoring System (NNMSS) and to evaluate this new instrument. A systematic review was undertaken in which 21 scoring instruments were reviewed and compared. None of the instruments studied satisfied the criteria that were established beforehand. The six most common items from the systematic review were selected for the new instrument. To test the NNMSS, pairs of experienced nurses assessed the oral cavity of 26 patients independently. Inter-observer reliability (Kappa), correlation between items (Spearman's rank-order correlations) and internal consistency of the instrument (Cronbach's alpha) were calculated. The usability was evaluated with a questionnaire. Cohen's weighted Kappa was within an acceptable range. Almost all correlations were statistically significant and in the predicted direction. The Cronbach's alpha coefficient indicated sufficient internal consistency. All nurses found the NNMSS user-friendly and suitable for day-to-day care. The NNMSS can be used as a valid, reliable and usable instrument in daily nursing practice.
  European Journal of Cancer Care 08/2006; 15(3):228-34. · 1.17 Impact Factor
• Article: A randomised, double-blinded, placebo-controlled, pilot study of parenteral glutamine for allogeneic stem cell transplant patients.

  N M A Blijlevens, J P Donnelly, A H J Naber, A V M B Schattenberg, B E DePauw
  [show abstract] [hide abstract]
  ABSTRACT: We conducted a prospective, randomised, double-blinded, placebo-controlled pilot study of parenteral nutrition (PN) supplemented with 0.57 g/kg glutamine-dipeptide in a homogeneous group of 32 allogeneic stem cell transplant (SCT) recipients to determine its effect on mucosal barrier injury (MBI). All patients had been prepared with idarubicin, cyclophosphamide and total body irradiation. PN (by continuous infusion) started on SCT day -6 for a median of 19 days. MBI measured by sugar permeability tests, daily mucositis score, daily gut score, and citrulline concentrations was not reduced by glutamine-dipeptide. However, the daily gut score was significantly lower for the glutamine group on SCT +7 (p = 0.001) whilst citrulline was lower (p = 0.03) for the placebo group on SCT day +21. Albumin was significantly lower in the placebo group on SCT day +21 (32+/-4 versus 37+/-3, p = 0.001) whilst CRP was higher (74+/-48 versus 34+/-38, p = 0.003). Other transplant-related complications (infections, acute graft-versus-host disease) were less common although this did not reach statistical significance nor translate into a reduced length of hospital stay or lower mortality. These results indicate that it would be worthwhile conducting a larger trial to see whether or not giving glutamine-dipeptide reduces the 100-day allogeneic transplant-related complications.
  Supportive Care Cancer 11/2005; 13(10):790-6. · 2.60 Impact Factor
• Article: Inflammatory response to mucosal barrier injury after myeloablative therapy in allogeneic stem cell transplant recipients.

  N M A Blijlevens, J P Donnelly, B E DePauw
  [show abstract] [hide abstract]
  ABSTRACT: We noted a significant increase of interleukin-8 (IL-8), LBP and CRP mirroring the pattern of mucosal barrier injury as measured by gut integrity (lactulose/rhamnose ratio), daily mucositis score (DMS) and serum citrulline concentrations of 32 haematopoietic stem cell transplant (HSCT) recipients following intensive myeloablative therapy. Concentrations of IL-8, LBP and CRP were already significantly elevated before the onset of fever or bacteraemia due to oral viridans streptococci (OVS) in the first week after transplant during profound neutropenia. These markers reached their peak when citrulline concentrations reached their nadir, the highest scores of DMS were attained and when there was significantly decreased gut integrity. This suggests that the degree of mucosal barrier injury rather than bacteraemia due to OVS determines the intensity of the inflammatory response.
  Bone Marrow Transplantation 11/2005; 36(8):703-7. · 3.75 Impact Factor