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Author Notes:

Michelle Schoettler, Children's Healthcare of Atlanta/Aflac Cancer and Blood Disorders Center, 1405 Clifton Rd, NE, Atlanta, GA 30322; Email: michelle.schoettler@emory.edu

Contribution: A.H. extracted data; M.S. designed the study, completed the analysis, and wrote the manuscript; S.C. and J.J. completed the complement marker analysis; S.C. and K.M.W. helped with study design and edited the manuscript; K.S., D.L., and S.R. extracted data from the medical record and helped edit the manuscript; E.S., S.P., M.Q., B.W., and K.L. edited the manuscript and cared for the patients; K.S., D.L., and S.R. manually extracted information from the medical chart, with other authors participating in the adjudication of 25% of randomly selected data in addition to TA-TMA and VOD diagnoses; and all authors performed chart audits to verify retrospective assignment of TA-TMA.

The authors acknowledge Matthew Magee, biostatistician, for reviewing the analysis.

S.C. has provided consultation to Agios, Alexion, Daichi Sankyo, Novartis, and Takeda and has received research funding from Alexion and Global Blood Therapeutics. The remaining authors declare no competing financial interests.


Research Funding:

This work was supported by funding from the National Institutes of Health Loan Repayment Program, the Aflac Pilot Award (M.S.), and the American Society of Hematology Scholar Award (S.C.).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Hematology

Sickle cell disease is a risk factor for transplant-associated thrombotic microangiopathy in children

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Journal Title:



Volume 7, Number 9


, Pages 1784-1795

Type of Work:

Article | Final Publisher PDF


Transplant-associated thrombotic microangiopathy (TA-TMA) and sickle cell disease (SCD) share features of endothelial and complement activation. Thus, we hypothesized that SCD is a risk factor for TA-TMA and that prehematopoietic cellular transplantation (HCT) markers of endothelial dysfunction and complement activation would be higher in patients with SCD. Children who underwent initial haploidentical or matched sibling donor HCT between January 2015 and June 2020 were included in this institutional review board–approved, single institution, retrospective study. Of the 115 children, 52 had SCD, and 63 underwent HCT for non-SCD indications. There was no significant difference in severe grade 3 to 4 acute graft-versus-host disease (GVHD) between recipients of HCT with or without SCD. The non-SCD cohort had significantly more cytomegalovirus-positive recipients, radiation-containing preparative regimens, and peripheral blood stem cell graft sources (P ≤ .05), all described risk factors for developing TA-TMA. Despite this, 7 of 52 patients (13%) with SCD developed TA-TMA compared with 1 of 63 patients (2%) without SCD (P = .015). Risk was highest in those who underwent haploidentical HCT (odds ratio [OR], 33; 95% confidence interval [CI], 1.4-793.2). Adjusting for HLA match, GVHD, post-HCT viral infection, stem cell source, and myeloablation, SCD remained a risk for developing TA-TMA (OR, 12.22; 95% CI, 1.15-129.6). In available pre-HCT samples, there was no difference in complement biomarkers between those with SCD and those without, though patients with SCD did have significantly higher levels of markers of endothelial activation, soluble vascular cell adhesion molecule 1, and P-selectin. In conclusion, children with SCD merit careful screening for TA-TMA after HCT, particularly those receiving a haploidentical HCT.

Copyright information:

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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