A diagnostic classifier for pediatric chronic graft-versus-host disease: results of the ABLE/PBMTC 1202 study

Geoffrey D.E. Cuvelier, Bernard Ng, Sayeh Abdossamadi, Eneida R. Nemecek, Alexis Melton, Carrie L. Kitko, Victor A. 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, Sonali Chaudhury, Donald Coulter, Joseph H. ChewningMichael Joyce, Süreyya Savaşan, Anna B. Pawlowska, Gail C. Megason, David Mitchell, Alexandra C. Cheerva, Anita Lawitschka, Elena Ostroumov, Kirk R. Schultz

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


The National Institutes of Health Consensus criteria for chronic graft-versus-host disease (cGVHD) diagnosis can be challenging to apply in children, making pediatric cGVHD diagnosis difficult. We aimed to identify diagnostic pediatric cGVHD biomarkers that would complement the current clinical criteria and help differentiate cGVHD from non-cGVHD. The Applied Biomarkers of Late Effects of Childhood Cancer (ABLE) study, open at 27 transplant centers, prospectively evaluated 302 pediatric patients after hematopoietic cell transplant (234 evaluable). Forty-four patients developed cGVHD. Mixed and fixed effect regression analyses were performed on diagnostic cGVHD onset blood samples for cellular and plasma biomarkers, with individual markers declared relevant if they met 3 criteria: an effect ratio ≥1.3 or ≤0.75; an area under the curve (AUC) of ≥0.60; and a P value <5.814 × 10−4 (Bonferroni correction) (mixed effect) or <.05 (fixed effect). To address the complexity of cGVHD diagnosis in children, we built a machine learning–based classifier that combined multiple cellular and plasma biomarkers with clinical factors. Decreases in regulatory natural killer cells, naïve CD4 T helper cells, and naïve regulatory T cells, and elevated levels of CXCL9, CXCL10, CXCL11, ST2, ICAM-1, and soluble CD13 (sCD13) characterize the onset of cGVHD. Evaluation of the time dependence revealed that sCD13, ST2, and ICAM-1 levels varied with the timing of cGVHD onset. The cGVHD diagnostic classifier achieved an AUC of 0.89, with a positive predictive value of 82% and a negative predictive value of 80% for diagnosing cGVHD. Our polyomic approach to building a diagnostic classifier could help improve the diagnosis of cGVHD in children but requires validation in future prospective studies.

Original languageEnglish (US)
Pages (from-to)3612-3623
Number of pages12
JournalBlood Advances
Issue number14
StatePublished - Jul 25 2023

ASJC Scopus subject areas

  • Hematology


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