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New insights into risk factors for transplant-associated thrombotic microangiopathy in pediatric HSCT.
Blood Adv. 2020 Jun 09; 4(11):2418-2429.BA

Abstract

This study aimed to identify a risk profile for development of transplant-associated thrombotic microangiopathy (TA-TMA) in children undergoing hematopoietic stem cell transplantation (HSCT). Between 2013 and 2016, 439 children underwent 474 HSCTs at 2 supraregional United Kingdom centers. At a median of 153 days post-HSCT, TA-TMA occurred among 25 of 441 evaluable cases (5.6%) with no evidence of center variation. Sex, underlying disease, intensity of the conditioning, total body irradiation-based conditioning, the use of calcineurin inhibitors, venoocclusive disease, and viral reactivation did not influence the development of TA-TMA. Donor type: matched sibling donor/matched family donor vs matched unrelated donor vs mismatched unrelated donor/haplo-HSCT, showed a trend toward the development of TA-TMA in 1.8% vs 6.1% vs 8.3%, respectively. Presence of active comorbidity was associated with an increased risk for TA-TMA; 13% vs 3.7% in the absence of comorbidity. The risk of TA-TMA was threefold higher among patients who received >1 transplant. TA-TMA rates were significantly higher among patients with acute graft-versus-host disease (aGVHD) grades III to IV vs aGVHD grade 0 to II. On multivariate analysis, the presence of active comorbidity, >1 transplant, aGVHD grade III to IV were risk factors for TA-TMA (odds ratio [OR]: 5.1, 5.2, and 26.9; respectively), whereas the use of cyclosporine A/tacrolimus-based GVHD prophylaxis was not a risk factor for TA-TMA (OR: 0.3). Active comorbidity, subsequent transplant, and aGVHD grades III to IV were significant risk factors for TA-TMA. TA-TMA might represent a form of a vascular GVHD, and therefore, continuing control of aGVHD is important to prevent worsening of TA-TMA associated with GVHD.

Authors+Show Affiliations

Department of Immunology and.Department of Blood and Marrow Transplantation, Great Ormond Street (GOS) Hospital for Children NHS Foundation Trust, University College London GOS Institute of Child Health, and NIHR GOSH BRC, London, United Kingdom.Host Defence Unit, The Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.Department of Paediatrics, Fondazione MBBM University of Milan-Bicocca, Monza, Italy.Hospital Pablo Tobon Uribe, Medellín, Colombia.Host Defence Unit, The Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.Host Defence Unit, The Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.Host Defence Unit, The Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.Host Defence Unit, The Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.Host Defence Unit, The Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.Host Defence Unit, The Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.Host Defence Unit, The Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.National Renal Complement Therapeutics Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.National Renal Complement Therapeutics Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.Department of Cellular Pathology, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom.Department of Blood and Marrow Transplantation, Great Ormond Street (GOS) Hospital for Children NHS Foundation Trust, University College London GOS Institute of Child Health, and NIHR GOSH BRC, London, United Kingdom.Department of Blood and Marrow Transplantation, Great Ormond Street (GOS) Hospital for Children NHS Foundation Trust, University College London GOS Institute of Child Health, and NIHR GOSH BRC, London, United Kingdom.Department of Blood and Marrow Transplantation, Great Ormond Street (GOS) Hospital for Children NHS Foundation Trust, University College London GOS Institute of Child Health, and NIHR GOSH BRC, London, United Kingdom.Department of Immunology and.Department of Immunology and.Host Defence Unit, The Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.Department of Blood and Marrow Transplantation, Great Ormond Street (GOS) Hospital for Children NHS Foundation Trust, University College London GOS Institute of Child Health, and NIHR GOSH BRC, London, United Kingdom.GOS Hospital for Children NHS Foundation Trust, University College London GOS Institute of Child Health, and NIHR GOSH BRC, London, United Kingdom; and.Host Defence Unit, The Great North Children's Hospital, Newcastle upon Tyne, United Kingdom. Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.Department of Immunology and.Host Defence Unit, The Great North Children's Hospital, Newcastle upon Tyne, United Kingdom. Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.Department of Blood and Marrow Transplantation, Great Ormond Street (GOS) Hospital for Children NHS Foundation Trust, University College London GOS Institute of Child Health, and NIHR GOSH BRC, London, United Kingdom.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32492158

Citation

Elfeky, Reem, et al. "New Insights Into Risk Factors for Transplant-associated Thrombotic Microangiopathy in Pediatric HSCT." Blood Advances, vol. 4, no. 11, 2020, pp. 2418-2429.
Elfeky R, Lucchini G, Lum SH, et al. New insights into risk factors for transplant-associated thrombotic microangiopathy in pediatric HSCT. Blood Adv. 2020;4(11):2418-2429.
Elfeky, R., Lucchini, G., Lum, S. H., Ottaviano, G., Builes, N., Nademi, Z., Battersby, A., Flood, T., Owens, S., Cant, A. J., Young, H., Greener, S., Walsh, P., Kavanagh, D., Annavarapu, S., Rao, K., Amrolia, P., Chiesa, R., Worth, A., ... Veys, P. (2020). New insights into risk factors for transplant-associated thrombotic microangiopathy in pediatric HSCT. Blood Advances, 4(11), 2418-2429. https://doi.org/10.1182/bloodadvances.2019001315
Elfeky R, et al. New Insights Into Risk Factors for Transplant-associated Thrombotic Microangiopathy in Pediatric HSCT. Blood Adv. 2020 Jun 9;4(11):2418-2429. PubMed PMID: 32492158.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - New insights into risk factors for transplant-associated thrombotic microangiopathy in pediatric HSCT. AU - Elfeky,Reem, AU - Lucchini,Giovanna, AU - Lum,Su-Han, AU - Ottaviano,Giorgio, AU - Builes,Natalia, AU - Nademi,Zohreh, AU - Battersby,Alexandra, AU - Flood,Terence, AU - Owens,Stephen, AU - Cant,Andrew J, AU - Young,Helen, AU - Greener,Sinéad, AU - Walsh,Patrick, AU - Kavanagh,David, AU - Annavarapu,Srinivas, AU - Rao,Kanchan, AU - Amrolia,Persis, AU - Chiesa,Robert, AU - Worth,Austen, AU - Booth,Claire, AU - Skinner,Roderick, AU - Doncheva,Bilyana, AU - Standing,Joseph, AU - Gennery,Andrew R, AU - Qasim,Waseem, AU - Slatter,Mary, AU - Veys,Paul, PY - 2019/12/06/received PY - 2020/04/16/accepted PY - 2020/6/4/entrez PY - 2020/6/4/pubmed PY - 2020/6/4/medline SP - 2418 EP - 2429 JF - Blood advances JO - Blood Adv VL - 4 IS - 11 N2 - This study aimed to identify a risk profile for development of transplant-associated thrombotic microangiopathy (TA-TMA) in children undergoing hematopoietic stem cell transplantation (HSCT). Between 2013 and 2016, 439 children underwent 474 HSCTs at 2 supraregional United Kingdom centers. At a median of 153 days post-HSCT, TA-TMA occurred among 25 of 441 evaluable cases (5.6%) with no evidence of center variation. Sex, underlying disease, intensity of the conditioning, total body irradiation-based conditioning, the use of calcineurin inhibitors, venoocclusive disease, and viral reactivation did not influence the development of TA-TMA. Donor type: matched sibling donor/matched family donor vs matched unrelated donor vs mismatched unrelated donor/haplo-HSCT, showed a trend toward the development of TA-TMA in 1.8% vs 6.1% vs 8.3%, respectively. Presence of active comorbidity was associated with an increased risk for TA-TMA; 13% vs 3.7% in the absence of comorbidity. The risk of TA-TMA was threefold higher among patients who received >1 transplant. TA-TMA rates were significantly higher among patients with acute graft-versus-host disease (aGVHD) grades III to IV vs aGVHD grade 0 to II. On multivariate analysis, the presence of active comorbidity, >1 transplant, aGVHD grade III to IV were risk factors for TA-TMA (odds ratio [OR]: 5.1, 5.2, and 26.9; respectively), whereas the use of cyclosporine A/tacrolimus-based GVHD prophylaxis was not a risk factor for TA-TMA (OR: 0.3). Active comorbidity, subsequent transplant, and aGVHD grades III to IV were significant risk factors for TA-TMA. TA-TMA might represent a form of a vascular GVHD, and therefore, continuing control of aGVHD is important to prevent worsening of TA-TMA associated with GVHD. SN - 2473-9537 UR - https://www.unboundmedicine.com/medline/citation/32492158/New_insights_into_risk_factors_for_transplant-associated_thrombotic_microangiopathy_in_pediatric_HSCT L2 - https://ashpublications.org/bloodadvances/article-lookup/doi/10.1182/bloodadvances.2019001315 DB - PRIME DP - Unbound Medicine ER -
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