Publications by authors named "Virginie De Wilde"

19 Publications

  • Page 1 of 1

Intravascular lymphoma presenting with hypoxaemia, platypnoea and lactic acidosis.

BMJ Case Rep 2021 Jun 23;14(6). Epub 2021 Jun 23.

Haematology, Erasmus Hospital, Brussels, Belgium.

Intravascular large B-cell lymphoma (IVLBCL) is an aggressive and rare type of diffuse extranodal B-cell lymphoma. Diagnosis and treatment are challenging and clinical presentation is variable. Physicians should be aware of this rare but life-threatening lymphoma without adenopathy and treatment should be promptly started. We describe the case of a 70-year-old woman who presented with general malaise, acute dyspnoea, platypnoea and lactic acidosis. Echocardiography revealed an extracardiac shunt, the cause of her orthodeoxia. The patient developed rapid liver failure and underwent liver biopsy. Anatomopathological findings suggested IVLBCL, non-germinal center type. She achieved complete remission after rituximab, cyclophosphamide, doxorubicin, vincristine, methylprednisolone chemotherapy but relapsed 1 year after initial presentation with multiple organ involvement. The patient's relapsed disease was treated with rituximab, iphosphamide, carboplatin, etoposide and she is still in complete remission 2 years later.
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http://dx.doi.org/10.1136/bcr-2020-241067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230943PMC
June 2021

Gonadal Function Recovery in Patients With Advanced Hodgkin Lymphoma Treated With a PET-Adapted Regimen: Prospective Analysis of a Randomized Phase III Trial (AHL2011).

J Clin Oncol 2021 Jun 22:JCO2100068. Epub 2021 Jun 22.

Department of Haematology, University Hospital F Mitterrand and Inserm UMR1231, Dijon, France.

Purpose: The prospective, randomized AHL2011 trial demonstrated that the use of the doxorubicin, bleomycin, vinblastine, and dacarbazine regimen (ABVD) after two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) in early responders on the basis of a positron emission tomography (PET)-driven strategy was safe and minimized toxicity compared with standard 6 BEACOPP cycles. This substudy investigated the benefit of this strategy in gonadal function and fertility in patients under 45 years old.

Methods: Ovarian function was assessed by serum measurement of follicle-stimulating hormone (FSH), estradiol, and anti-müllerian hormone in women, and semen analysis, FSH, and testosterone levels were used to evaluate testicular function in men at baseline, end of treatment, and during 5 years of follow-up.

Results: A total of 145 women and 424 men, enrolled between May 19, 2011, and April 29, 2014, were included. The risk of premature ovarian insufficiency (FSH > 24 IU/L) and of having a low ovarian reserve (anti-müllerian hormone < 0.5 ng/mL) was reduced after treatment in the PET-driven group (odds ratio [OR], 0.20; 95% CI, 0.08 to 0.50; = .001 and OR, 0.15; 95% CI, 0.04 to 0.56, = .005, respectively). Both parameters were correlated with age and dose of alkylating agents. However, no significant differences were observed in terms of pregnancy rates. Men in the PET-driven group had a higher recovery rate of sperm parameters after treatment compared with the standard BEACOPP group, as well as a lower risk of severe testicular damage (OR, 0.26; 95% CI, 0.13 to 0.5; < .0001) and a higher likelihood of achieving pregnancy (OR, 3.7; 95% CI, 1.4 to 9.3; = .004).

Conclusion: Although both treatments affected ovarian reserve and spermatogenesis, the PET-driven strategy decreased the risk of gonadal dysfunction and infertility in advanced Hodgkin lymphoma.
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http://dx.doi.org/10.1200/JCO.21.00068DOI Listing
June 2021

Case Report of an Unusual Tumor in an Adult With a TP53 Germline Mutation.

Clin Lymphoma Myeloma Leuk 2020 Dec 31. Epub 2020 Dec 31.

Department of Hematology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.

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http://dx.doi.org/10.1016/j.clml.2020.10.001DOI Listing
December 2020

Autologous stem cell transplantation for post-transplant lymphoproliferative disorders after solid organ transplantation: a retrospective analysis from the Lymphoma Working Party of the EBMT.

Bone Marrow Transplant 2021 Apr 16. Epub 2021 Apr 16.

Lymphoma Working Party EBMT, Paris, France.

Published data describing the efficacy and safety of autologous stem-cell transplantation (autoSCT) in post-transplant lymphoproliferative disorders (PTLD) is limited to case reports. This is a retrospective analysis of 21 patients reported to the EBMT registry who received an autoSCT for PTLD post solid organ transplant (SOT). Median age at autoSCT was 47 (range: 22-71) years. The commonest SOTs were kidney (48%) and liver (24%). Commonest histologies included DLBCL-type PTLD (14/21) and plasmacytoma-like PTLD (3/21). Patients received a median of two lines of therapy (range: 1-4) pre-autoSCT. ECOG performance status pre-autoSCT was 0 in 14% and 1 in 86%. Remission status pre-autoSCT was CR 47% and PR 38%. BEAM conditioning was used in 57% and high-dose melphalan in 10%. The median follow-up post-autoSCT was 64 months for alive patients. 3-year PFS was 62% [95% confidence interval (CI) 44-87%] and 3-year OS was 61% [95% CI:43-86]. There were 12 deaths, including four related to autoSCT. 100-day non-relapse-mortality (NRM) was 14% and 1-year NRM was 24%. This study suggests that autoSCT, although feasible and with potential therapeutic activity, is associated with a high NRM, primarily driven by infectious toxicity. A multi-disciplinary approach, expert microbiological input and stringent patient selection are required to optimise outcomes.
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http://dx.doi.org/10.1038/s41409-021-01270-5DOI Listing
April 2021

Moderate forms of COVID-19 among healthcare workers in a Belgian hospital and their immune response.

Acta Clin Belg 2021 Mar 24:1-9. Epub 2021 Mar 24.

Department of Hematology, CUB Hôpital Erasme, Université Libre De Bruxelles, Brussels, Belgium.

Introduction: Healthcare professionals have been treating patients with COVID-19 since the pandemic started in early 2020 while also trying to limit disease spread among their coworkers and communities. This study aimed to identify and follow potentially infected healthcare workers in one hospital in order to develop an epidemiological baseline for COVID-19 infection and spread rates in this population.

Materials And Methods: This prospective study was conducted between 1 April and 30 June 2020 at a single Belgian hospital. Healthcare workers with symptoms consistent with COVID-19 were included. Participants underwent testing for SARS-CoV-2 infection by nasopharyngeal (NP) swab and analysis of blood samples for antibody response at different timepoints (day 0, 7, 14 and day 30 or 60). Patient exposures, symptoms, and disease progression were collected.

Results: Of a total of 150 healthcare workers with symptoms compatible with SARS-CoV-2 infection, 31% (47) tested positive for the virus by NP swab. Of the 47 participants with positive NP swabs, 66% also had positive IgG serology. Of the 99 participants with negative NP swabs who underwent blood sample collection, 5% had positive IgG serology results. Of the 29 participants who presented with at least 3 major symptoms, 15 (52%) had positive NP swabs and 14 (48%) had positive serology.

Conclusions: This study demonstrates that evidence of symptoms, even when major, is a poor predictor for SARS-CoV-2 positivity in health care workers and raises the question of the best way to efficiently screen this population especially during the upcoming flu period.
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http://dx.doi.org/10.1080/17843286.2021.1899695DOI Listing
March 2021

Donor-Derived Myeloid Heme Oxygenase-1 Controls the Development of Graft-Versus-Host Disease.

Front Immunol 2020 18;11:579151. Epub 2021 Jan 18.

Institute for Medical Immunology, Université Libre de Bruxelles, Gosselies, Belgium.

Graft-versus-host disease (GVHD) remains a major clinical drawback of allogeneic hematopoietic stem cell transplantation (HSCT). Here, we investigated how the stress responsive heme catabolizing enzyme heme oxygenase-1 (HO-1, encoded by ) regulates GVHD in response to allogeneic hematopoietic stem cell transplantation in mice and humans. We found that deletion of the allele, specifically in the myeloid compartment of mouse donor bone marrow, promotes the development of aggressive GVHD after allogeneic transplantation. The mechanism driving GVHD in mice transplanted with allogeneic bone marrow lacking HO-1 expression in the myeloid compartment involves enhanced T cell alloreactivity. The clinical relevance of these observations was validated in two independent cohorts of HSCT patients. Individuals transplanted with hematopoietic stem cells from donors carrying a long homozygous (GT) repeat polymorphism (L/L) in the promoter, which is associated with lower HO-1 expression, were at higher risk of developing severe acute GVHD as compared to donors carrying a short (GT) repeat (S/L or S/S) polymorphism associated with higher HO-1 expression. In this study, we showed the unique importance of donor-derived myeloid HO-1 in the prevention of lethal experimental GVHD and we corroborated this observation by demonstrating the association between human (GT) microsatellite polymorphisms and the incidence of severe acute GVHD in two independent HSCT patient cohorts. Donor-derived myeloid HO-1 constitutes a potential therapeutic target for HSCT patients and large-scale prospective studies in HSCT patients are necessary to validate the HO-1 L/L genotype as an independent risk factor for developing severe acute GVHD.
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http://dx.doi.org/10.3389/fimmu.2020.579151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849683PMC
June 2021

Delayed Thrombotic Complications in a Thrombotic Thrombocytopenic Purpura Patient Treated With Caplacizumab.

J Hematol 2020 Sep 14;9(3):84-88. Epub 2020 Aug 14.

Hematology Department, Erasme Hospital, Brussels, Belgium.

Thrombotic thrombocytopenic purpura (TTP) is a rare and unpredictable disease with a high mortality rate (90%) if untreated. It results from systemic microvascular thrombosis and leads to profound thrombocytopenia, hemolytic anemia and organ failure of varying severity. However, macrovascular thrombosis has been described in very rare cases. Caplacizumab has emerged as a promising new drug for the management of TTP. We report the case of a patient with idiopathic refractory TTP treated with caplacizumab who developed thrombotic complications upon discontinuation of treatment.
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http://dx.doi.org/10.14740/jh614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430863PMC
September 2020

Unexplained cause of thrombocytopenia, fever, anasarca and hypothyroidism: TAFRO syndrome with thrombotic microangiopathy renal histology.

BMJ Case Rep 2020 Jun 30;13(6). Epub 2020 Jun 30.

Heamatology, Hopital Erasme, Brussels, Belgium.

TAFRO (thrombocytopenia, anasarca, fever, reticulin myelofibrosis or renal dysfunction and organomegaly) syndrome is a systemic inflammatory disease characterised by thrombocytopenia, anasarca, fever or inflammatory syndrome, reticulin myelofibrosis or renal dysfunction and organomegaly. It was first described as a subtype of idiopathic multicentric Castleman disease. Here, we report the case of a 42-year-old woman presenting with thrombocytopenia, anasarca, inflammatory syndrome, renal insufficiency, reticulin myelofibrosis at bone marrow biopsy and cervical and axillary lymph nodes. Kidney biopsy showed double contours of the glomerular basement membrane, mesangiolysis and endothelial swelling compatible with thrombotic microangiopathy (TMA) as well as with TAFRO syndrome. She was successfully treated by corticosteroids, tocilizumab and rituximab. This new case description of TAFRO syndrome underlines three features of this disease rarely described in the literature and never simultaneously in the same patient: the association to severe hypothyroidism, the presence of TMA-like lesions on kidney biopsy and the treatment by the association of steroids, tocilizumab and rituximab.
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http://dx.doi.org/10.1136/bcr-2019-234155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328895PMC
June 2020

Acquired hemophilia A revealed by spontaneous bleeding in an 80-year-old man: a marginal diagnosis?

Acta Clin Belg 2020 May 27:1-3. Epub 2020 May 27.

Department of Hematology, Hôpital Erasme, Université Libre De Bruxelles, Brussels, Belgium.

This case report illustrates the difficulty associated with diagnosing acquired hemophilia A by reviewing the case of an 80-year-old man admitted to the hospital for anemia. A prolonged activated partial thromboplastin time (aPTT) was not noticed until the patient developed a severe hemorrhagic syndrome.
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http://dx.doi.org/10.1080/17843286.2020.1768735DOI Listing
May 2020

Pituitary Gland and Neurological Involvement in a Case of Hemophagocytic Syndrome Revealing an Intravascular Large B-Cell Lymphoma.

Case Rep Hematol 2019 28;2019:9625075. Epub 2019 Apr 28.

Department of Internal Medicine, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.

Intravascular large B-cell lymphoma is a rare entity characterized by the proliferation of neoplastic lymphocytes in the lumen of small blood vessels and high mortality. Diagnosis of intravascular lymphoma is often delayed or established postmortem. Here, we report the case of a 48-year-old woman presenting hemophagocytic syndrome, with pituitary gland and neurological involvement. Diagnosis of intravascular large B-cell lymphoma was made on perisplenic vessels, while liver and bone marrow biopsy was noncontributive. This case demonstrates the importance of thorough histopathologic investigations in the setting of high suspicion.
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http://dx.doi.org/10.1155/2019/9625075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512020PMC
April 2019

Providing both autologous and allogeneic hematopoietic stem cell transplants (HSCT) may have a stronger impact on the outcome of autologous HSCT in adult patients than activity levels or implementation of JACIE at Belgian transplant centres.

Bone Marrow Transplant 2019 09 29;54(9):1434-1442. Epub 2019 Jan 29.

CHU de Liège, Liège, Belgium.

While performance since the introduction of the JACIE quality management system has been shown to be improved for allogeneic hematopoietic stem cell transplants (HSCT), impact on autologous-HSCT remains unclear in Europe. Our study on 2697 autologous-HSCT performed in adults in 17 Belgian centres (2007-2013) aims at comparing the adjusted 1 and 3-yr survival between the different centres & investigating the impact of 3 centre-related factors on performance (time between JACIE accreditation achievement by the centre and the considered transplant, centre activity volume and type of HSCT performed by centres: exclusively autologous vs both autologous & allogeneic). We showed a relatively homogeneous performance between Belgian centres before national completeness of JACIE implementation. The 3 centre-related factors had a significant impact on the 1-yr survival, while activity volume and type of HSCT impacted the 3-yr survival of autologous-HSCT patients in univariable analyses. Only activity volume (impact on 1-yr survival only) and type of HSCT (impact on 1 and 3-yr survivals) remained significant in multivariable analysis. This is explained by the strong relationship between these 3 variables. An extended transplantation experience, i.e., performing both auto & allo-HSCT, appears to be a newly informative quality indicator potentially conveying a multitude of underlying complex factors.
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http://dx.doi.org/10.1038/s41409-019-0458-8DOI Listing
September 2019

The Light Chain IgLV3-21 Defines a New Poor Prognostic Subgroup in Chronic Lymphocytic Leukemia: Results of a Multicenter Study.

Clin Cancer Res 2018 10 26;24(20):5048-5057. Epub 2018 Jun 26.

Molecular Diagnostic Centre, Oxford University Hospitals, Oxford, United Kingdom.

Unmutated (UM) immunoglobulin heavy chain variable region (IgHV) status or IgHV3-21 gene usage is associated with poor prognosis in chronic lymphocytic leukemia (CLL) patients. Interestingly, IgHV3-21 is often co-expressed with light chain IgLV3-21, which is potentially able to trigger cell-autonomous BCR-mediated signaling. However, this light chain has never been characterized independently of the heavy chain IgHV3-21. We performed total RNA sequencing in 32 patients and investigated IgLV3-21 prognostic impact in terms of treatment-free survival (TFS) and overall survival (OS) in 3 other independent cohorts for a total of 813 patients. IgLV3-21 presence was tested by real-time PCR and confirmed by Sanger sequencing. Using total RNA sequencing to characterize 32 patients with high-risk CLL, we found a high frequency (28%) of IgLV3-21 rearrangements. Gene set enrichment analysis revealed that these patients express higher levels of genes responsible for ribosome biogenesis and translation initiation ( < 0.0001) as well as MYC target genes ( = 0.0003). Patients with IgLV3-21 rearrangements displayed a significantly shorter TFS and OS ( < 0.05), particularly those with IgHV mutation. In each of the three independent validation cohorts, we showed that IgLV3-21 rearrangements-similar to UM IgHV status-conferred poor prognosis compared with mutated IgHV ( < 0.0001). Importantly, we confirmed by multivariate analysis that this was independent of IgHV mutational status or subset #2 stereotyped receptor ( < 0.0001). We have demonstrated for the first time that a light chain can affect CLL prognosis and that IgLV3-21 light chain usage defines a new subgroup of CLL patients with poor prognosis. .
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http://dx.doi.org/10.1158/1078-0432.CCR-18-0133DOI Listing
October 2018

A Belgian consensus protocol for autologous hematopoietic stem cell transplantation in multiple sclerosis.

Acta Neurol Belg 2018 Jun 13;118(2):161-168. Epub 2018 Mar 13.

Department of Hematology, Antwerp University Hospital, Wilrijkstraat 10, 2650, Edegem, Belgium.

Multiple sclerosis is considered to be an immune mediated inflammatory disorder of the central nervous system. It mainly affects young, socioeconomic active patients. Although our armamentarium for this disease has significantly evolved in recent years some patients remain refractory to conventional therapies. In these cases, autologous hematopoietic stem cell transplantation can be considered as a therapeutic option. Decreasing morbidity, mortality, and increasing patient awareness have led to rising inquiry by our patients about this treatment option. With the aim of a standardized protocol and data registration, a Belgian working party on stem cell therapy in multiple sclerosis was established. In this paper, we report the consensus protocol of this working party on autologous hematopoietic stem cell transplantation in multiple sclerosis.
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http://dx.doi.org/10.1007/s13760-018-0905-0DOI Listing
June 2018

Clonal eosinophil and mast cell diseases: different in the same way?

Expert Rev Hematol 2016 12 17;9(12):1107-1109. Epub 2016 Nov 17.

c Department of Clinical Hematology , Assistance Publique-Hôpitaux de Paris, Hôpital Necker , Paris , France.

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http://dx.doi.org/10.1080/17474086.2016.1254036DOI Listing
December 2016

Interleukin 17-producing T helper cells in alloimmunity.

Transplant Rev (Orlando) 2009 Jan;23(1):11-8

Institute for Medical Immunology, Université Libre de Bruxelles, 6041 Gosselies, Belgium.

Interleukin (IL) 17 is a proinflammatory cytokine already known to play a defense role against microbes and a pathogenic role in a number of autoimmune diseases. Although IL-17 can be produced by a variety of cells including neutrophils, CD8+, NK, and gamma-delta T cells, the concept of IL-17-secreting CD4+ T helper cells (Th17), distinct from Th1 and Th2, recently emerged. Herein, we discuss arguments in favor of a Th17-mediated alternative pathway of allograft rejection based on clinical and experimental observations drawn from the literature. We also discuss the complex interplays among regulatory T cells and Th17 cells in the allogeneic context.
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http://dx.doi.org/10.1016/j.trre.2008.08.007DOI Listing
January 2009

The multiple facets of toll-like receptors in transplantation biology.

Transplantation 2008 Jul;86(1):1-9

Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL, USA.

Toll-like receptors (TLRs) belong to a family of pattern-recognition receptors for microbial products and endogenous molecules released by stressed cells. Experimental studies show that TLRs are involved in the process of acute allograft rejection and that their activation can prevent transplantation tolerance. Herein, we review the expression of TLRs and the impact of TLR signaling in different cell types in grafted organs including antigen-presenting cells, T and B lymphocytes, epithelial and endothelial cells. We then discuss the involvement of TLRs in the different phases of the rejection phenomenon and the impact of TLR-mediated events on regulatory circuits which dampen alloimmune responses.
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http://dx.doi.org/10.1097/TP.0b013e31817c11e6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4423792PMC
July 2008

IL-17 production elicited by allo-major histocompatibility complex class II recognition depends on CD25posCD4pos T cells.

Transplantation 2008 Apr;85(7):943-9

Fonds National de la Recherche Scientifique, Belgium.

Background: Interleukin (IL)-17 is involved in autoimmune inflammatory disorders and naturally occurring CD25pos regulatory T cells were shown to promote IL-17 synthesis. Because IL-17 is overproduced in certain types of allograft rejection, it is important to characterize the cells responsible for IL-17 synthesis and to define how IL-17 is regulated during alloimmune responses.

Methods: Splenic CD4pos T cells were isolated from C57BL/6 mice and fractionated according to CD25 expression. T cells were stimulated by major histocompatibility complex class II-mismatched bone marrow-derived dendritic cells from bm12 mice, either immature or made mature by exposure to lipopolysaccharide. To track T cell populations, CD25negCD4pos and CD25posCD4pos were isolated from Thy1.1 and congenic Thy1.2 mice, respectively. Cell proliferation was quantified by CFSE dilution. IL-17-producing cells and FOXP3pos cells were enumerated by intracytoplasmic staining and cytokine levels in culture supernatants were measured by ELISA.

Results: Addition of CD25posCD4pos T cells to CD25negCD4pos T cells inhibited IL-2, interferon-[gamma], and IL-13 production but promoted IL-17 synthesis on stimulation by allogenic immature DC. In this setting, IL-17 originated from CD25intCD4posFOXP3neg memory T cells, which depend on IL-2 to produce IL-17. Alloreactive CD25negCD4pos T cells were also induced to produce IL-17 when stimulated by mature DC in the presence of CD25highCD4posFOXP3pos T cells.

Conclusions: We conclude that (1) the cellular source of IL-17 during an antiallo major histocompatibility complex class II response depends on the maturation status of allogenic DC, (2) whereas suppressing Th1 and Th2 cytokine synthesis, naturally occurring regulatory T cells, allow IL-17 production by alloreactive CD4pos T cells.
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http://dx.doi.org/10.1097/TP.0b013e31816a5ae7DOI Listing
April 2008

Endotoxin hyperresponsiveness upon CD4+ T cell reconstitution in lymphopenic mice: control by natural regulatory T cells.

Eur J Immunol 2008 Jan;38(1):48-53

Institute for Medical Immunology, Université Libre de Bruxelles, Gosselies, Belgium.

Natural CD4(+)CD25(+) regulatory T cells (nTreg) have been shown to control graft-versus-host disease after hematopoietic stem cell transplantation (HSCT). Herein, we considered the possibility that the beneficial action of nTreg upon immune reconstitution in lymphopenic hosts involves dampening of the inflammatory response induced by bacterial products. We first observed that transfer of syngeneic CD4(+)CD25(-) T cells in RAG-deficient mice dramatically enhanced release of inflammatory cytokines and associated pathology upon endotoxin injection. Interferon (IFN)-gamma produced by T cells undergoing homeostatic proliferation was shown to be involved in the endotoxin hyperresponsiveness induced by CD4(+) T cell reconstitution. Co-transfer of CD4(+)CD25(+) nTreg with CD4(+)CD25(-) T cells inhibited the expansion of IFN-gamma-producing T cells and reduced endotoxin responses in RAG(-/-) mice. We conclude that (1) CD4(+) T cell reconstitution sensitizes lymphopenic hosts to endotoxin-induced pathology and (2) nTreg prevent this process by limiting the emergence of IFN-gamma-producing cells.
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http://dx.doi.org/10.1002/eji.200737534DOI Listing
January 2008
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