6 results on '"Leavis, Helen L"'
Search Results
2. Severe thrombotic microangiopathy after autologous stem cell transplantation in systemic sclerosis: a case report.
- Author
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Sharif MO, Leavis HL, van Paassen P, van Rhenen A, Timmermans SAMEG, Ton E, Laar JMV, and Spierings J
- Subjects
- Fatal Outcome, Humans, Middle Aged, Thrombotic Microangiopathies immunology, Transplantation, Autologous, Hematopoietic Stem Cell Transplantation methods, Scleroderma, Systemic therapy, Thrombotic Microangiopathies etiology
- Published
- 2021
- Full Text
- View/download PDF
3. Allogeneic stem cell transplantation in a patient with myelodysplastic syndrome and polyarteritis nodosa: a case report and systematic review.
- Author
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Stavenga M, Leavis HL, de Witte TM, and Raymakers RA
- Subjects
- Humans, Male, Middle Aged, Myelodysplastic Syndromes diagnosis, Polyarteritis Nodosa diagnosis, Hematopoietic Stem Cell Transplantation methods, Myelodysplastic Syndromes complications, Myelodysplastic Syndromes therapy, Polyarteritis Nodosa complications, Polyarteritis Nodosa therapy
- Published
- 2016
- Full Text
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4. Clinical Symptoms, Laboratory Parameters and Long-Term Follow-up in a National DADA2 Cohort.
- Author
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Andriessen, Marie Valérie E., Legger, G. Elizabeth, Bredius, Robbert G. M., van Gijn, Marielle E., Hak, A. Elisabeth, Muller, Petra C. E. Hissink, Kamphuis, Sylvia, Klouwer, Femke C. C., Kuijpers, Taco W., Leavis, Helen L., Nierkens, Stefan, Rutgers, Abraham, van der Veken, Lars T., van Well, Gijs T. J., Mulders-Manders, Catharina M., and van Montfrans, Joris M.
- Subjects
HEMATOPOIETIC stem cell transplantation ,BASAL cell carcinoma ,SYMPTOMS ,HEMOPHAGOCYTIC lymphohistiocytosis ,AUTOINFLAMMATORY diseases - Abstract
Deficiency of adenosine deaminase-2 (DADA2) is an autosomal recessive autoinflammatory disease with an extremely variable disease presentation. This paper provides a comprehensive overview of the Dutch DADA2 cohort. We performed a retrospective cohort study in 29 ADA2-deficient patients from 23 families with a median age at inclusion of 26 years. All patients had biallelic pathogenic variants in the ADA2 gene. The most common clinical findings included cutaneous involvement (79.3%), (hepato)splenomegaly (70.8%) and recurrent infections (58.6%). Stroke was observed in 41.4% of the patients. The main laboratory abnormalities were hypogammaglobulinemia and various cytopenias. Patients presented most often with a mixed phenotype involving vasculopathy, immunodeficiency and hematologic manifestations (62.1%). In this cohort, malignancies were reported in eight patients (27.6%), of whom five presented with a hematologic malignancy and two with a basal cell carcinoma. Four patients developed hemophagocytic lymphohistiocytosis (HLH) or an HLH-like episode, of whom three passed away during or shortly after the occurrence of HLH. TNF-inhibitors (TNFi) were effective in treating vasculopathy-associated symptoms and preventing stroke, but were hardly effective in the treatment of hematologic manifestations. Three patients underwent hematopoietic cell transplantation and two of them are doing well with complete resolution of DADA2-related symptoms. The overall mortality in this cohort was 17.2%. In conclusion, this cohort describes the clinical, genetic and laboratory findings of 29 Dutch DADA2 patients. We describe the occurrence of HLH as a life-threatening disease complication and report a relatively high incidence of malignancies and mortality. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
5. Broad Virus Detection and Variant Discovery in Fecal Samples of Hematopoietic Transplant Recipients Using Targeted Sequence Capture Metagenomics.
- Author
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Jansen, Suze A., Nijhuis, Wouter, Leavis, Helen L., Riezebos-Brilman, Annelies, Lindemans, Caroline A., and Schuurman, Rob
- Subjects
NOROVIRUSES ,NOROVIRUS diseases ,METAGENOMICS ,HEMATOPOIETIC stem cell transplantation ,VIRAL gastroenteritis ,VIRUS diseases ,GRAFT versus host disease ,DIAGNOSTIC use of polymerase chain reaction - Abstract
Pediatric allogeneic hematopoietic stem cell transplantation (HSCT) patients often suffer from gastro-intestinal (GI) disease caused by viruses, Graft-versus-Host Disease (GVHD) or a combination of the two. Currently, the GI eukaryotic virome of HSCT recipients remains relatively understudied, which complicates the understanding of its role in GVHD pathogenicity. As decisions regarding immunosuppressive therapy in the treatment of virus infection or GVHD, respectively, can be completely contradicting, it is crucial to better understand the prevalence and relevance of viruses in the GI tract in the HSCT setting. A real time PCR panel for a set of specific viruses widely used to diagnose the most common causes of GI viral gastroenteritis is possibly insufficient to grasp the full extent of viruses present. Therefore, we applied the targeted sequence capture method ViroCap to residual fecal samples of 11 pediatric allogeneic HSCT recipients with GI symptoms and a suspicion of GVHD, to enrich for nucleic acids of viruses that are known to infect vertebrate hosts. After enrichment, NGS was applied to broadly detect viral sequences. Using ViroCap, we were able to detect viruses such as norovirus and adenovirus (ADV), that had been previously detected using clinical diagnostic PCR on the same sample. In addition, multiple, some of which clinically relevant viruses were detected, including ADV, human rhinovirus (HRV) and BK polyomavirus (BKV). Interestingly, in samples in which specific PCR testing for regular viral GI pathogens did not result in a diagnosis, the ViroCap pipeline led to the detection of viral sequences of human herpesvirus (HHV)-7, BKV, HRV, KI polyomavirus and astrovirus. The latter was an only recently described variant and showed extensive sequence mismatches with the applied real time PCR primers and would therefore not have been detected if tested. Our results indicate that target enrichment of viral nucleic acids through ViroCap leads to sensitive and broad possibly clinically relevant virus detection, including the detection of newer variants in clinical HSCT recipient samples. As such, ViroCap could be a useful detection tool clinically, but also in studying the associations between viral presence and GVHD. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
6. Targeted Sequence Capture Metagenomics (ViroCap) to Detect Viruses in Stool Samples of Hematopoietic Stem Cell Transplantation Patients.
- Author
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Jansen, Suze A., Nijhuis, Wouter, Leavis, Helen L., Riezebos-Brilman, Annelies, Lindemans, Caroline A., and Schuurman, Rob
- Subjects
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HEMATOPOIETIC stem cell transplantation , *CHLOROPLAST DNA , *METAGENOMICS , *DNA viruses , *VIRUSES , *HEMATOPOIETIC system - Abstract
Gastro-intestinal (GI) symptoms in pediatric allogeneic hematopoietic stem cell transplantation (HSCT) patients are common and may be caused by viruses, Graft-Versus-Host-Disease (GVHD) or both. Currently, little is known about the GI viriome in SCT patients, hindering the study of the pathogenicity and role in GVHD. We used ViroCap, a viral target enrichment method, in combination with Next Generation Sequencing (NGS) to detect viruses in stool samples of HSCT patients and compared to PCR results. Using ViroCap, nucleic acid of a broad range of RNA and DNA viruses infecting vertebrate hosts was enriched in banked stool samples of HSCT patients. Upon enrichment, samples were sequenced by NGS on an Illumina MiSeq system and detected viral sequences were analyzed using the automated Genome Detective pipeline (GD) and/or directly aligned (DA) to a reference sequence of a specific virus, using Genious software. Where possible, presence of newly detected viral pathogens was confirmed by virus-specific qPCR. Stool samples of 11 patients, age range 1-17, that had undergone HSCT for a variety of indications were selected for ViroCap analysis. All selected patients suffered from GI-symptoms. Ten were diagnosed with grade I-IV GI-GVHD according to consensus guidelines. In 6 samples adenovirus (ADV), norovirus or both had been previously detected by clinical diagnostic qPCRs (Diagnosis D), while in 5 samples no viral GI pathogens were found (No diagnosis ND). In all D samples the presence of the initially found virus could be confirmed upon ViroCap analysis. ADV was most commonly found and Ct values grossly correlated with the number of sequence specific reads upon ViroCap GD and DA analysis. In addition, ViroCap led to the detection of multiple, possibly clinically relevant viral pathogens in D samples, including human herpesvirus-6B (HHV6B) (n=1), BK polyomavirus (BKV) (n=2), ADV (n=1) and human rhinovirus (HRV) (n=1). Presence of BKV and HRV was confirmed by qPCR. Furthermore, in 4/5 ND samples viral pathogens were detected. These included human herpes Virus 7 (HHV7) (n=1), BKV (n=1), HRV (n=2) and Astrovirus (AV) (n=1). HRV presence was confirmed by qPCR, HHV7 was not tested. BKV could not be confirmed, but other clinical samples from the same patient taken closely before/after the specific stool sample were BKV positive. Further analysis of the AV sequences revealed that the routine PCR failed to detect this virus due to extensive sequence mismatches in the primer/probe binding regions. This AV clade was classified as an AV VA3 (JX857868.1). In summary, application of viral target enrichment strategies with limited pathogen detection bias, such as ViroCap, increase the sensitivity of NGS for virus detection and can lead to discovery of novel variants. As such, it might be a useful screening tool to study associations of viral pathogens with GI-symptoms and GVHD. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
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