medwireNews: Researchers have identified decreases in subpopulations of naïve CD4+ helper T cells, regulatory T cells (Tregs), and regulatory natural killer (NK) cells that could provide an early warning sign of chronic graft-versus-host disease (GvHD) in children.

Presenting the findings at the virtual 62nd American Society of Hematology Annual Meeting and Exposition, Geoff Cuvelier (CancerCare Manitoba, Winnipeg, Canada) commented that while the US National Institutes of Health (NIH) consensus criteria provide a gold standard for diagnosing chronic GvHD in children, they are “adult-centric in nature.”

He noted that “experienced pediatric transplant physicians still struggle with diagnosing chronic GvHD,” adding that “diagnosing chronic GvHD in children at the onset of the disorder when physical manifestations may still be in evolution and are often uncertain to the clinician is particularly challenging.”

A total of 302 pediatric transplant patients younger than 18 years of age were prospectively enrolled to the ABLE/PBMTC 1202 study between 2013 and 2017 and followed up for chronic GvHD in the year after hematopoietic stem cell transplantation for any indication, malignant (69%) or benign (31%). The participants could be receiving any conditioning regimen and any GvHD prophylactic treatment strategy. 

Blood samples drawn at the onset of chronic GvHD according to NIH consensus criteria, before escalation of immune therapy, were available for 43 of these patients and these were compared with blood samples from children without chronic GvHD drawn at 100 days, 6 months, and 12 months.

The researchers found that children with chronic GvHD had significantly decreased levels of subpopulations of naïve helper T cells, Treg cells, and regulatory NK cells, with an effect size below 0.7 and an area under the receiver operator characteristic curve of at least 0.6, compared with controls.

The same subpopulations were decreased in both patients diagnosed before 120 days and after 240 days, Cuvelier notes, suggesting the findings are independent of timing of chronic GvHD onset.

Looking further at the cell subtypes within these cell populations, Cuvelier reported that CD4+ and CD45RA+ naïve helper T cells were significantly decreased among children with chronic GvHD relative to controls, regardless of the coexpression of other cell markers.

“This suggests that any one or more of these subpopulations could be relevant diagnostic biomarkers for pediatric chronic GvHD,” he said.

The findings also showed a relevant naïve Treg subpopulation that co-expressed CD45RA but also CD31, which is a “marker of recent emigration out of the thymus,” Cuvelier explained. This could mean pediatric chronic GvHD is “characterized by a relative decrease in thymopoiesis and more specifically the inability of the thymus to produce regulatory T cells.” 

The relevant naïve regulatory NK cells included subpopulations that expressed high levels of CD56 and CD335 but low levels of perforin.

Despite small numbers, there was also some evidence of different biomarker patterns in two subtypes of pediatric chronic GvHD. Specifically, patients with de novo chronic GvHD had significant decreases in activated and cytolytic NK cells, whereas patients with progressive (overlap syndrome) chronic GvHD were characterized by increases in activated NK cells together with B-cell lymphopenia and decreases in naïve T3 transitional B cells, mature naïve B cells, and naïve helper T cells.

Cuvelier concluded that the cell populations identified in the study may be suitable diagnostic biomarkers of pediatric chronic GvHD, with “the promise to potentially help pediatric clinicians arrive at a concise diagnosis of chronic GvHD in the early phase of the illness.”

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62nd ASH Annual Meeting and Exposition; 5–8 December 2020