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Benefits and challenges with diagnosing chronic and late acute GvHD in children using the NIH consensus criteria

Geoffrey D.E. Cuvelier, Eneida R Nemecek, Justin T Wahlstrom, Carrie L Kitko, Victor Anthony Lewis, Tal Schechter, David A Jacobsohn, Andrew C. Harris, Michael A Pulsipher, Henrique Bittencourt, Sung Won Choi, Emi H Caywood, Kimberly A Kasow, Monica Bhatia, Benjamin R Oshrine, Allyson Flower, Sonali Chaudhury, Donald Coulter, Joseph H Chewning, Michael Joyce, Süreyya Savaşan, Anna B Pawlowska, Gail C Megason, David Mitchell, Alexandra C Cheerva, Anita Lawitschka, Lori J West, Bo Pan, Yazid N Al-Hamarneh, Anat Halevy and Kirk R Schultz

Key Points

  • Using central review in a multi-institution study, 28.2% of submitted cGvHD cases in children were re-classified using the NIH-CC.

  • The NIH-CC are feasible and reliable for children, but further refinement of criteria specifically for pediatric cGvHD is needed.

Abstract

Chronic graft-versus-host disease (cGvHD) and late-acute GvHD (L-aGvHD) are understudied complications of allogeneic hematopoietic stem cell transplantation in children. The National Institutes of Health Consensus Criteria (NIH-CC) were designed to improve the diagnostic accuracy of cGvHD and better classify GvHD syndromes but have not been validated in patients <18-years of age. The objectives of this prospective, multi-institution study were to determine: (1) if the NIH-CC could be used to diagnose pediatric cGvHD and whether the criteria operationalize well in a multi-institution study; (2) the frequency of cGvHD and L-aGvHD in children using the NIH-CC; and (3) the clinical features and risk factors for cGvHD and L-aGvHD using the NIH-CC. Twenty-seven transplant centers enrolled 302 patients <18 years before conditioning and prospectively followed them for 1-year post-transplant for development of cGvHD. Centers justified their cGvHD diagnosis according to the NIH-CC using central review and a study adjudication committee. 28.2% of reported cGvHD cases were re-classified, usually as L-aGvHD, following study committee review. Similar incidence of cGvHD and L-aGvHD was found (21% and 24.7%, respectively). The most common organs involved with diagnostic or distinctive manifestations of cGvHD in children include the mouth, skin, eyes, and lungs. Importantly, the 2014 NIH-CC for bronchiolitis obliterans syndrome perform poorly in children. Past acute GvHD and peripheral blood grafts are major risk factors for cGvHD and L-aGvHD, with recipients above 12-years being at risk for cGvHD. Applying the NIH-CC in pediatrics is feasible and reliable, however, further refinement of the criteria specifically for children is needed.

  • Submitted February 18, 2019.
  • Revision received April 25, 2019.
  • Accepted April 25, 2019.