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Open AccessArticle

Incidence of Capillary Leak Syndrome as an Adverse Effect of Drugs in Cancer Patients: A Systematic Review and Meta-Analysis

College of Medicine, Gyeongsang National University, Jinju 52727, Korea
Department of Pediatrics, Yonsei University College of Medicine, Yonsei-ro 50, Seodaemun-gu, C.P.O., Box 8044, Seoul 03722, Korea
Division of Pediatric Nephrology, Severance Children’s Hospital, Seoul 03722, Korea
Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul 03722, Korea
Wonkwang University School of Medicine, Iksan 54538, Korea
Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, 6020 Innsbruck, Austria
Luton& Dunstable University Hospital NHS Foundation Trust, Lewsey Road, Luton LU4 ODZ, UK
Department of Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands
Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt
Department of Oncology, University of Calgary, Tom Baker Cancer Centre, Calgary, AB T2N 1N4, Canada
Institute of Psychiatry, Psychology and Neuroscience, King’s College London, De Crespigny Park, London SE5 8AF, UK
South London and Maudsley NHS Foundation Trust, Denmark Hill, London SE5 8AZ, UK
Faculty of Health, Social Care and Education, Anglia Ruskin University, Chelmsford CM1 1SQ, UK
Department of Neuroscience, University of Padova, 35121 Padova, Italy
National Research Council, Neuroscience Institute, 35128 Padova, Italy
Pain and Rehabilitation Centre, and Department of Medical and Health Sciences, Linköping University, SE-581 85 Linköping, Sweden
Parc Sanitari Sant Joan de Déu/CIBERSAM, Universitat de Barcelona, Fundació Sant Joan de Déu, Sant Boi de Llobregat, 08830 Barcelona, Spain
Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
Mental Health Research Networking Center (CIBERSAM), 08036 Barcelona, Spain
Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE5 8AF, UK
Centre for Psychiatric Research, Department of Clinical Neuroscience, Karolinska Institutet, 113 30 Stockholm, Sweden
Author to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(2), 143;
Received: 7 December 2018 / Revised: 9 January 2019 / Accepted: 21 January 2019 / Published: 26 January 2019
(This article belongs to the Section Vascular Medicine)
Capillary leak syndrome (CLS) is a rare disease with profound vascular leakage, which can be associated with a high mortality. There have been several reports on CLS as an adverse effect of anti-cancer agents and therapy, but the incidence of CLS according to the kinds of anti-cancer drugs has not been systemically evaluated. Thus, the aim of our study was to comprehensively meta-analyze the incidence of CLS by different types of cancer treatment or after bone marrow transplantation (BMT). We searched the literatures (inception to July 2018) and among 4612 articles, 62 clinical trials (studies) were eligible. We extracted the number of patients with CLS, total cancer patients, name of therapeutic agent and dose, and type of cancer. We performed a meta-analysis to estimate the summary effects with 95% confidence interval and between-study heterogeneity. The reported incidence of CLS was categorized by causative drugs and BMT. The largest number of studies reported on CLS incidence during interleukin-2 (IL-2) treatment (n = 18), which yielded a pooled incidence of 34.7% by overall estimation and 43.9% by meta-analysis. The second largest number of studies reported on anti-cluster of differentiation (anti-CD) agents (n = 13) (incidence of 33.9% by overall estimation and 35.6% by meta-analysis) or undergoing BMT (n = 7 (21.1% by overall estimation and 21.7% by meta-analysis). Also, anti-cancer agents, including IL-2 + imatinib mesylate (three studies) and anti-CD22 monoclinal antibodies (mAb) (four studies), showed a dose-dependent increase in the incidence of CLS. Our study is the first to provide an informative overview on the incidence rate of reported CLS patients as an adverse event of anti-cancer treatment. This meta-analysis can lead to a better understanding of CLS and assist physicians in identifying the presence of CLS early in the disease course to improve the outcome and optimize management. View Full-Text
Keywords: capillary leak syndrome; cancer; interleukin-2; anti-CD agents; bone marrow transplantation capillary leak syndrome; cancer; interleukin-2; anti-CD agents; bone marrow transplantation
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Jeong, G.H.; Lee, K.H.; Lee, I.R.; Oh, J.H.; Kim, D.W.; Shin, J.W.; Kronbichler, A.; Eisenhut, M.; van der Vliet, H.J.; Abdel-Rahman, O.; Stubbs, B.; Solmi, M.; Veronese, N.; Dragioti, E.; Koyanagi, A.; Radua, J.; Shin, J.I. Incidence of Capillary Leak Syndrome as an Adverse Effect of Drugs in Cancer Patients: A Systematic Review and Meta-Analysis. J. Clin. Med. 2019, 8, 143.

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