A study evaluating late effects of allogeneic hematopoietic cell transplantation (HCT) on pediatric survivors of cancer suggests that chronic graft-versus-host disease (cGVHD) is associated with nonmalignant effects, but not with subsequent neoplasms (SNs). SNs, however, were linked to myeloablative total body irradiation. These study results were recently reported in the journal Transplantation and Cellular Therapy.

Many children who undergo allogeneic HCT develop cGVHD, “and given their longer life expectancy, there is a pressing need to understand the impact of cGVHD on late effects in this vulnerable population,” the study investigators explained in their report.

The researchers performed a systematic, retrospective study based on data from the Center for International Blood and Marrow Transplant Research to characterize late effects experienced by children with cGVHD. Included patients had a first allogeneic HCT with myeloablative conditioning between the years of 2000 and 2010 for a hematologic malignancy, and they had reached 2 or more years of disease-free survival after HCT.

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Cumulative incidences of first malignant and nonmalignant late effects in these survivors were evaluated, with analyses based on outcomes for patients with and without cGVHD. Risk factors for first late effects were also examined.

Among 1260 survivors included in this study, the 2-year incidence of cGVHD after HCT was 39%. The 10-year cumulative incidence of any late effect was estimated to be 43% for survivors with cGVHD, compared with 32% for survivors without cGVHD (P <.001). A multivariate analysis suggested that cGVHD 2 years after HCT was associated with the presence of any late effect (hazard ratio [HR], 1.38; 95% CI, 1.13-1.68; P =.001).

Presence of cGVHD 2 years after HCT was not associated with SN (HR, 1.30; 95% CI, 0.73-2.31; P =.38). However, cGVHD at 2 years post-HCT was associated with nonmalignant late effects (HR, 1.37; 95% CI, 1.10-1.70; P =.006).

In multivariate analyses, the researchers found that severe cGVHD (HR, 2.25; 95% CI, 1.60-3.17; P <.0001) was associated with nonmalignant late effects, as was extensive-grade cGVHD (HR, 1.60; 95% CI, 1.23-2.08; P =.0005), and interrupted onset-type cGVHD (HR, 1.57; 95% CI, 1.21-2.05; P =.0008). The presence of both mucocutaneous and visceral involvement in cGVHD was also associated with nonmalignant late effects (HR, 1.59; 95% CI, 1.24-2.03; P =.0002).

Although cGVHD was not associated with the onset of SN, total body irradiation was associated with SN (HR, 16.59; 95% CI, 2.21-124.25; P =.006). Total body irradiation was also associated with nonmalignant late effects (HR, 1.80; 95% CI, 1.39-2.33; P <.0001).

“Future research should continue upon this work and re-evaluate the impact of cGVHD on late effects using the 2014 National Institutes of Health consensus criteria for cGVHD,” the researchers concluded in their report.

Disclosures: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Lee CJ, Wang T, Chen K, et al. Association of chronic graft-versus-host disease with late effects following allogeneic hematopoietic cell transplantation for children with hematologic malignancy. Transplant Cell Ther. Published online July 18, 2022. doi:10.1016/j.jtct.2022.07.014