Rob Fijnheer

Meander Medisch Centrum, Amersfoort, Utrecht, Netherlands

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Publications (170)792.27 Total impact

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    ABSTRACT: There is a lack of data on the effect of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy on brain glucose metabolism of diffuse large B-cell lymphoma (DLBCL) patients, as measured by 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Moreover, the prognostic value of brain glucose metabolism measurements is currently unknown. To investigate the use of FDG-PET for measurement of brain glucose metabolism in R-CHOP-treated DLBCL patients, and to assess its prognostic value. This retrospective study included DLBCL patients who underwent FDG-PET including the brain. FDG-PET metabolic volume products (MVPs) of the entire brain, cerebral cortex, basal ganglia, and cerebellum were measured, before and after R-CHOP therapy. Whole-body total lesion glycolysis (TLG) was also measured. Thirty-eight patients were included, of whom 18 had an appropriate end-of-treatment FDG-PET scan. There were no significant differences (P > 0.199) between pre- and post-treatment brain glucose metabolism metrics. Low basal ganglia MVP was associated with a significantly worse progression-free survival (PFS) and overall survival (OS) (P = 0.020 and P = 0.032), and low cerebellar MVP was associated with a significantly worse OS (P = 0.034). There were non-significant very weak correlations between pretreatment brain glucose metabolism metrics and TLG. In the multivariate Cox regression, only the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) remained an independent predictor of PFS (hazard ratio 3.787, P = 0.007) and OS (hazard ratio 2.903, P = 0.0345). Brain glucose metabolism was not affected by R-CHOP therapy. Low pretreatment brain glucose metabolism was associated with a worse outcome, but did not surpass the predictive value of the NCCN-IPI. © The Foundation Acta Radiologica 2015.
    Acta Radiologica 08/2015; DOI:10.1177/0284185115598809 · 1.35 Impact Factor
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    ABSTRACT: This study aimed to determine the prognostic value of residual anatomical disease, including its size and reduction relative to baseline, in diffuse large B-cell lymphoma patients who have F-fluoro-2-deoxy-D-glucose positron emission tomography-based complete response after first-line R-CHOP therapy. This retrospective study included 47 patients. In patients with computed tomography (CT)-based residual disease, the size of the largest residual lesion (Resmax) and the sum of the sizes of all residual lesions (Restotal) were measured, and their reductions relative to baseline (ΔResmax and ΔRestotal) were calculated. Patients with high-risk National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) scores had significantly lower progression-free survival (PFS) and overall survival (OS) than patients with low-risk NCCN-IPI scores (P = 0.032 and P = 0.022). In contrast, patients with residual lesions at CT had no significantly lower PFS and OS than those without (P = 0.531 and P = 0.801). In the subpopulation with CT-based residual disease, patients with high Resmax, high Restotal, low ΔResmax, and low ΔRestotal had no significantly different PFS and OS than those with low Resmax, low Restotal, high ΔResmax, and high ΔRestotal (P = 0.980 and P = 0.790, P = 0.423 and P = 0.229, P = 0.923 and P = 0.893, and P = 0.923 and P = 0.893, respectively). The NCCN-IPI retains its prognostic value in diffuse large B-cell lymphoma patients with F-fluoro-2-deoxy-D-glucose positron emission tomography-based complete response after first-line R-CHOP therapy. However, the presence of residual anatomical disease, including its size and reduction relative to baseline, has no prognostic value in these patients.
    Journal of computer assisted tomography 05/2015; DOI:10.1097/RCT.0000000000000270 · 1.60 Impact Factor
  • Acta oncologica (Stockholm, Sweden) 05/2015; DOI:10.3109/0284186X.2015.1041652 · 3.71 Impact Factor
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    ABSTRACT: To assess the performance of whole-body MRI including diffusion-weighted imaging (whole-body MRI-DWI) for the detection of residual disease after completion of treatment in lymphoma patients. Twenty-six patients with lymphoma prospectively underwent whole-body MRI-DWI (1.5 Tesla MR) and 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET)/computed tomography (CT) for posttreatment evaluation which were visually assessed. Apparent diffusion coefficient (ADC) and FDG-PET/CT standardized uptake value measurements were performed in all residual lesions. An unblinded expert panel reviewed all cases and determined the presence or absence of posttreatment residual disease using all available imaging (except for whole-body MRI-DWI), clinical, and histopathological information with a follow-up of at least 6 months. The performance of whole-body MRI-DWI was compared with this panel reference standard. Five of 26 patients were diagnosed with residual disease. Sensitivity and specificity for detection of residual disease with whole-body MRI-DWI were 100% and 62%, respectively. By ROC analysis, the optimal threshold of ADC was 1.21 × 10(-3) mm(2) /s with sensitivity and specificity of 100% and 91.7%, respectively. Our initial results suggest that visual whole-body MRI-DWI analysis has a very good sensitivity for detecting viable residual lesions after completion of therapy but lacks specificity. ADC measurements could potentially increase the specificity of whole-body MRI. J. Magn. Reson. Imaging 2015. © 2015 Wiley Periodicals, Inc.
    Journal of Magnetic Resonance Imaging 05/2015; DOI:10.1002/jmri.24938 · 2.79 Impact Factor
  • American Journal of Hematology 03/2015; 90(3). DOI:10.1002/ajh.23921 · 3.48 Impact Factor
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    ABSTRACT: Platelets and platelet-monocyte interaction play an important role in inflammation. Both pro- and anti-inflammatory effects of platelet inhibition have been reported in animal models. This study aimed to investigate the effect of platelets and platelet inhibition by the new P2Y12 receptor antagonist ticagrelor on monocyte function, as assessed by cytokine responses to Toll-like Receptor (TLR) ligands. In a set of in vitro experiments, peripheral blood mononuclear cells (PBMC) incubated with the TLR2 ligand Pam3CSK4 produced less cytokines in the presence of platelets, whereas platelets increased the production of cytokines when PBMC were exposed to TLR4 ligand lipopolysaccharide (LPS). These effects of platelets were dependent on direct platelet-leukocyte aggregation and for the Pam3CSK4-induced response, on phagocytosis of platelets by monocytes. In a double blind, placebo-controlled crossover trial in healthy volunteers, a single oral dosage of 180 mg ticagrelor reduced platelet-monocyte complex (PMC) formation. This was associated with an increase in pro-inflammatory cytokines in blood exposed to Pam3CSK4, but a decrease in these cytokines in blood exposed to LPS. These findings show that platelets differentially modulate TLR2- and TLR4-mediated cytokine responses of PBMC. Through inhibition of platelet-leukocyte interaction, P2Y12 receptor antagonists may either exert a pro- or anti-inflammatory effect during infections depending on the TLR primarily involved.
    Thrombosis and Haemostasis 02/2015; 113(5). DOI:10.1160/TH14-07-0579 · 5.76 Impact Factor
  • American Journal of Hematology 02/2015; 90(7). DOI:10.1002/ajh.23986 · 3.48 Impact Factor
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    ABSTRACT: Accurate evaluation of the spleen is an important component of staging lymphoma, because this may have prognostic and therapeutic implications. To determine the diagnostic value of whole-body magnetic resonance imaging (MRI), including diffusion-weighted imaging (whole-body MRI-DWI) in the detection of splenic involvement in lymphoma. This IRB approved, prospective multicenter study included a total of 107 patients with newly diagnosed, histologically proven lymphoma who underwent 1.5 T whole-body MRI-DWI and FDG-PET/CT. Whole-body MRI-DWI and FDG-PET/CT were independently evaluated by a radiologist and a nuclear medicine physician, in a blinded manner. Splenic involvement at MRI was defined as splenic index > 725 cm(3) or discrete nodules. At FDG-PET/CT splenic involvement was defined as splenic uptake greater than liver uptake or hypodense nodules at contrast-enhanced CT. FDG-PET/CT augmented with follow-up imaging after treatment was used as reference standard. Splenic involvement was detected with FDG-PET/CT in 21 patients, all demonstrating response to treatment. The sensitivity, specificity, positive predictive value, and negative predictive value of whole-body MRI-DWI for the detection of splenic involvement were 85.7 %, 96.5 %, 85.7%, and 96.5%, respectively. Three out of six discrepancies were related to suboptimal criterion of splenic size used with whole-body MRI-DWI versus the size-independent FDG uptake. Whole-body MRI-DWI is reasonably accurate in the detection of splenic lymphomatous involvement. © The Foundation Acta Radiologica 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
    Acta Radiologica 02/2015; DOI:10.1177/0284185115571657 · 1.35 Impact Factor
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    ABSTRACT: To determine the prognostic value of tumor-induced cortical bone destruction at computed tomography (CT) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). This retrospective study included 105 patients with newly diagnosed DLBCL who had undergone CT and bone marrow biopsy (BMB) before R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, Oncovin, and prednisolone) chemo-immunotherapy. Cox regression analyses were used to determine the associations of cortical bone status at CT (absence vs. presence of tumor-induced cortical bone destruction), BMB findings (negative vs. positive for lymphomatous involvement), and dichotomized National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) strata (low risk vs. high risk) with progression-free survival (PFS) and overall survival (OS). Univariate Cox regression analysis indicated that cortical bone status at CT was no significant predictor of either PFS or OS (p = 0.358 and p = 0.560, respectively), whereas BMB findings (p = 0.002 and p = 0.013, respectively) and dichotomized NCCN-IPI risk strata (p = 0.002 and p = 0.003, respectively) were significant predictors of both PFS and OS. In the multivariate Cox proportional hazards model, only the dichotomized NCCN-IPI score was an independent predictive factor of PFS and OS (p = 0.004 and p = 0.003, respectively). The presence of tumor-induced cortical bone destruction at CT was not found to have any prognostic implications in newly diagnosed DLBCL.
    Skeletal Radiology 02/2015; 44(5). DOI:10.1007/s00256-015-2102-z · 1.74 Impact Factor
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    ABSTRACT: This study compared CT-based and (18)F-fluoro-2-deoxy-D-glucose PET/CT (FDG-PET/CT)-based NCCN International Prognostic Index (NCCN-IPI) risk stratification in newly diagnosed diffuse large B-cell lymphoma (DLBCL). This retrospective study included 57 patients with newly diagnosed DLBCL who had undergone both (oral and intravenous contrast-enhanced full-dose) diagnostic CT and FDG-PET/CT. Diagnostic CT only and FDG-PET/CT were evaluated separately, and corresponding NCCN-IPI scores for the 2 datasets (NCCN-IPICT and NCCN-IPIPET/CT) were calculated. Percentages of agreement and weighted k statistic between NCCN-IPICT and NCCN-IPIPET/CT scoring with regard to the formation of low-, low-intermediate-, high-intermediate-, and high-risk groups were calculated. In 47 of 57 patients (82.5%; 95% CI, 70.4-90.4), diagnostic CT alone was in agreement with FDG-PET/CT with regard to the formation of low-, low-intermediate-, high-intermediate-, and high-risk NCCN-IPI groups, but not in the remaining 10 patients (17.5%; 95% CI, 9.6%-29.6%). All NCCN-IPI disagreements between diagnostic CT and FDG-PET/CT were from the detection of additional lesions by the latter, most of them being bone marrow lesions. Agreement between NCCN-IPICT and NCCN-IPIPET/CT with regard to the formation of low-, low-intermediate-, high-intermediate-, and high-risk groups was considered good (k=0.771). Although agreement between NCCN-IPICT and NCCN-IPIPET/CT risk stratification is generally good, FDG-PET/CT results in higher NCCN-IPI risk stratifications in a non-negligible proportion of patients. Future studies should investigate the prognostic implications of these imaging-based differences in NCCN-IPI scoring. Copyright © 2015 by the National Comprehensive Cancer Network.
    Journal of the National Comprehensive Cancer Network: JNCCN 02/2015; 13(2):171-6. · 4.24 Impact Factor
  • Circulation 01/2015; 131(2):e19-e20. DOI:10.1161/CIRCULATIONAHA.114.012802 · 14.95 Impact Factor
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    ABSTRACT: To determine the incidence of diffusely increased bone marrow (18) F-fluoro-2-deoxy-D-glucose (FDG) uptake at positron emission tomography (PET) in recently untreated lymphoma, and to assess the frequency of lymphoma-positive bone marrow biopsies (BMBs) in these patients. FDG-PET scans of all patients presenting with newly diagnosed or relapsed lymphoma were reviewed. Patients with non-focal, diffusely increased bone marrow FDG uptake, who had not received therapy within three months, were identified. The incidences of diffusely increased bone marrow FDG uptake, and the frequencies of positive posterior iliac crest BMBs among those cases were calculated. The incidences of diffusely increased bone marrow FDG uptake in all lymphomas, and in Hodgkin lymphoma, aggressive non-Hodgkin lymphoma (NHL), indolent NHL, and mantle cell NHL separately, were 4.2% (23/542), 9.3% (7/75), 3.4% (8/239), 3.3% (7/214), and 7.1% (1/14), respectively, and frequencies of positive BMBs among these subgroups were 55.0% (11/20), 0.0% (0/7), 83.3% (5/6), 83.3% (5/6), and 100% (1/1), respectively. The incidence of diffusely increased bone marrow FDG uptake in recently untreated lymphoma is low, albeit higher in Hodgkin lymphoma than in NHL. BMB in such patients is likely to be negative in Hodgkin lymphoma, but positive in the majority of NHL cases. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    European Journal Of Haematology 12/2014; 95(1). DOI:10.1111/ejh.12483 · 2.41 Impact Factor
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    ABSTRACT: Objective: To determine the prognostic value of tumor necrosis at computed tomography (CT) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). Materials and methods: This retrospective study included 51 patients with newly diagnosed DLBCL who had undergone both unenhanced and intravenous contrast-enhanced CT before R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone) chemo-immunotherapy. Presence of tumor necrosis was visually and quantitatively assessed at CT. Associations between tumor necrosis status at CT and the National Comprehensive Cancer Network (NCCN) International Prognostic Index (IPI) factors were assessed. Cox regression analysis was used to determine the prognostic impact of NCCN-IPI scores and tumor necrosis status at CT. Results: There were no correlations between tumor necrosis status at CT and the NCCN-IPI factors categorized age (rho = -0.042, P = 0.765), categorized lactate dehydrogenase (LDH) ratio (rho = 0.201, P = 0.156), extranodal disease in major organs (phi= -0.245, P=0.083), Ann Arbor stage III/IV disease (phi = -0.208, P=0.141), and Eastern Cooperative Oncology Group (ECOG) performance status(phi = 0.015, P= 0.914). In the multivariate Cox proportional hazards model, only tumor necrosis status at CT was an independent predictive factor of progression-free survival (P=0.003) and overall survival (P= 0.004). Conclusion: The findings of this study indicate the prognostic potential of tumor necrosis at CT in newly diagnosed DLBCL.
    European Journal of Radiology 12/2014; 84(3). DOI:10.1016/j.ejrad.2014.12.009 · 2.16 Impact Factor
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    ABSTRACT: Detection of bone marrow involvement using 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) has been proposed as a non-invasive alternative to standard blind bone marrow biopsy (BMB) of the posterior iliac crest in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). However, studies that directly compare FDG-PET/CT results with histopathology are currently lacking.
    Acta Radiologica 11/2014; pii. DOI:10.1177/0284185114554824 · 1.35 Impact Factor
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    ABSTRACT: Purpose To directly compare visual and quantitative 18F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) to bone marrow biopsy (BMB) findings in the right posterior iliac crest in patients with newly diagnosed Hodgkin lymphoma. Materials and methods This retrospective study included 26 patients with newly diagnosed Hodgkin lymphoma in whom FDG-PET/CT was performed before BMB of the right posterior iliac crest. The right posterior iliac crest was assessed for bone marrow involvement, both visually and semi-quantitatively [using maximum standardized uptake value (SUVmax) measurements]. BMB of right the posterior iliac crest was used as reference standard. Results BMB of the right posterior iliac crest was positive in 5 (19.2 %) of 26 patients. There was full agreement between visual FDG-PET/CT and BMB findings in the right posterior iliac crest (i.e. no false-positive or false-negative FDG-PET/CT findings). Accordingly, sensitivity, specificity, positive predictive value, and negative predictive value of visual FDG-PET/CT assessment for the detection of bone marrow involvement in the right posterior iliac crest were 100 % (5/5) (95 % CI 51.1-100 %), 100 % (21/21) (95 % CI 81.8-100 %), 100 % (5/5) (95 % CI 51.1-100 %), and 100 % (21/21) (95 % CI 81.8-100 %), respectively. SUVmax of BMB-positive cases (mean ± SD: 3.4 ± 0.85) was nearly significantly higher (P = 0.052) than that of BMB-negative cases (mean ± SD 2.7 ± 0.63). Conclusion This histopathological correlation study confirms the very high diagnostic value of FDG-PET/CT in the detection of bone marrow involvement in newly diagnosed Hodgkin lymphoma, and supports the substitution of BMB with FDG-PET/CT in this setting.
    Annals of Nuclear Medicine 10/2014; 29(2). DOI:10.1007/s12149-014-0920-z · 1.51 Impact Factor
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    ABSTRACT: PurposeThis study aimed to determine the prognostic value of whole-body maximum standardized uptake value (SUVmax), whole-body metabolic tumor volume (MTV), and whole-body total lesion glycolysis (TLG) at pretreatment 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL).Materials and Methods73 patients with newly diagnosed DLBCL who had undergone FDG-PET/CT before rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone (R-CHOP) immunochemotherapy were retrospectively included. All FDG-avid lesions in each patient were segmented using semi-automated software in order to calculate whole-body SUVmax, whole-body MTV, and whole-body TLG values. Cox regression analyses were used to determine the associations of whole-body SUVmax, whole-body MTV, whole-body TLG, and dichotomized National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) risk group (low risk vs. high risk) with progression-free survival (PFS) and overall survival (OS).ResultsOn univariate Cox regression analysis, only the NCCN-IPI was a significant predictor of PFS (P=0.024), and only the NCCN-IPI and whole-body MTV were significant predictors of OS (P=0.039 and P=0.043, respectively). In the multivariate Cox proportional hazards model, only the NCCN-IPI remained an independent predictive factor of PFS (P=0.024) and OS (P=0.039).Conclusion Whole-body SUVmax, whole-body MTV, and whole-body TLG do not provide any prognostic information in DLBCL beyond that which can already be obtained by the NCCN-IPI. Therefore, the NCCN-IPI remains the most important prognostic tool in this disease.This article is protected by copyright. All rights reserved.
    European Journal Of Haematology 10/2014; 94(6). DOI:10.1111/ejh.12467 · 2.41 Impact Factor
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    ABSTRACT: Purpose. To determine the additional value of bone marrow biopsy (BMB) in the standard staging work-up of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), in terms of risk assessment and treatment planning. Material and methods. A total of 113 consecutive patients with newly diagnosed DLBCL who had undergone standard pretreatment evaluation, including serum lactate dehydrogenase measurement, Eastern Cooperative Oncology Group performance status assessment, computed tomography or (18)F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography, and BMB, were retrospectively included. National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) score and treatment strategy were determined in each patient, once without and once with taking into account BMB results. Numbers and percentages of BMB-induced changes on NCCN-IPI-based risk stratification (i.e. formation of low, low-intermediate, high-intermediate, and high risk groups) and choice of treatment were calculated, along with 95% confidence intervals (CIs). Results. BMB was positive in 18 of 113 patients (15.9%, 95% CI 10.2-23.9 %). BMB-induced changes on NCCI-IPI-based risk stratification occurred in 9 of 113 patients (8.0%, 95% CI 4.1-14.6%). Five patients were upstaged from low-intermediate to high-intermediate risk, and four patients were upstaged from high-intermediate to high risk. BMB findings changed treatment planning in none of the 113 patients (0.0%, 95% CI 0.0-4.0%). Conclusion. Although BMB results upstaged the NCCN-IPI-based risk stratification in a small number of cases, this did not have any therapeutic implications in our patient series. These findings support the omission of BMB from routine staging of newly diagnosed DLBCL in the current risk stratification and treatment era.
    Acta oncologica (Stockholm, Sweden) 09/2014; 54(1):1-6. DOI:10.3109/0284186X.2014.958531 · 3.71 Impact Factor
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    ABSTRACT: Platelets are key cells in atherosclerosis and acute cardiovascular events. Platelet hyperreactivity and increased platelet-monocyte aggregation (PMA) are found in HIV-infected patients and may contribute to the excess cardiovascular risk. The integrase inhibitor raltegravir (RAL) has been associated with better residual viral suppression and reduction in inflammatory and coagulation biomarkers. The aim of our study was to investigate whether RAL-treated patients have reduced platelet reactivity and PMA.
    AIDS (London, England) 09/2014; 28(14):2091-2096. DOI:10.1097/QAD.0000000000000415 · 6.56 Impact Factor
  • Hematological Oncology 09/2014; DOI:10.1002/hon.2167 · 2.36 Impact Factor

Publication Stats

4k Citations
792.27 Total Impact Points

Institutions

  • 2009–2015
    • Meander Medisch Centrum
      Amersfoort, Utrecht, Netherlands
  • 1999–2014
    • University Medical Center Utrecht
      • • Department of Hematology
      • • Department of Radiology
      • • Department of Clinical Chemistry and Haematology
      Utrecht, Utrecht, Netherlands
  • 2012
    • Jeroen Bosch Ziekenhuis
      Hertogenbosch, North Brabant, Netherlands
  • 2011
    • HagaZiekenhuis van Den Haag
      's-Gravenhage, South Holland, Netherlands
  • 1996–2007
    • Utrecht University
      • Department of Hematology
      Utrecht, Utrecht, Netherlands
  • 2005
    • CSU Mentor
      Long Beach, California, United States
  • 1989–1991
    • University of Amsterdam
      • Central Laboratory of the Netherlands Red Cross Blood Transfusion Service
      Amsterdamo, North Holland, Netherlands
  • 1990
    • Hong Kong Red Cross Blood Transfusion Service
      Hong Kong, Hong Kong