Pediatric acute graft‐versus‐host disease prophylaxis and treatment: surveyed real‐life approach reveals dissimilarities compared to published recommendations

Abstract

Summary Pediatric allogeneic hematopoietic cell transplantation (HCT) practices differ from those of adults, particularly the heterogeneity of transplantable nonmalignant diseases and the lower incidence of graft‐versus‐host disease (GVHD). Several guidelines regarding the management of acute (a) GVHD in adult HCT have been published. We aimed to capture the real‐life approaches for pediatric aGVHD prophylaxis/treatment, and data from 75/193 (response rate 39%) EBMT centers (26 countries) were included, representing half (48%) of the pediatric EBMT‐HCT activity. Results with ≥75% approval from respondents (74/75) for GVHD prophylaxis after myeloablative HCT for malignancies partially contradict published guidelines: Single‐agent cyclosporine A (CsA) was used for matched sibling donor HCT in 47%; blood CsA levels were reported lower; the relapse risk in malignant diseases influenced GVHD prophylaxis with early withdrawal of CsA; distinct longer duration of CsA was employed in nonmalignant diseases. Most centers used additional anti‐thymocyte globulin for matched unrelated and mismatched donor HCT, but not for matched siblings. Regarding prophylaxis in nonmyeloablative conditioning (mainly for nonmalignant diseases), responses showed broad heterogeneity. High conformity was found for first‐line treatment; however, results regarding steroid‐refractory aGVHD indicate an earlier diagnosis in children. Our findings highlight the need for standardized pediatric approaches toward aGVHD prophylaxis/treatment differentiated for malignant and nonmalignant underlying diseases.

The gut microbiome in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation

“…Pediatric patients have a lower risk of developing acute GvHD (aGvHD) than adults; however, this risk is still significant and the associated long-term sequelae of this complication and its treatment may be dramatic in children due to the possible impact on growth. 35,36 The complex interplay between intestinal mucosa damage, dendritic cells, and alloreactive T cells is influenced by particular variations of the GM architecture after HSCT, which can either promote or protect against aGvHD. 37 In pediatric patients who develop aGvHD, several changes occur after allogeneic HSCT, such as: (a) depletion of commensal anaerobes, particularly those belonging to the order Clostridiales, including the well-known health-promoting butyrate producer Faecalibacterium;…”

“…Pediatric patients have a lower risk of developing acute GvHD (aGvHD) than adults; however, this risk is still significant and the associated long‐term sequelae of this complication and its treatment may be dramatic in children due to the possible impact on growth 35,36 . The complex interplay between intestinal mucosa damage, dendritic cells, and alloreactive T cells is influenced by particular variations of the GM architecture after HSCT, which can either promote or protect against aGvHD 37 .…”

Analyzing the clinical outcomes of switching from cyclosporine to tacrolimus in pediatric hematopoietic stem cell transplantation

“…1,[11][12][13][14][15][16] Although these studies show that tacrolimus is efficacious and tolerable in children, CSA maintains to be the main drug in GvHD prophylaxis of pediatric hematopoietic stem cell transplantation. 17,18 Even though CSA and tacrolimus are both CNI and have a similar mechanism of effect, 19 there are unpublished experiences with switching CSA to tacrolimus due to different reasons in HSCT. The only article expressing the results of this type of switching involves only adults 20 and there is a lack of data for the pediatric population.…”

“…Despite the increasing use of tacrolimus in adults, there are limited studies about the efficacy and safety of tacrolimus in children 1,11‐16 . Although these studies show that tacrolimus is efficacious and tolerable in children, CSA maintains to be the main drug in GvHD prophylaxis of pediatric hematopoietic stem cell transplantation 17,18 …”

Az allogén vérképző őssejtátültetés korai szövődményei gyermekkorban

“…A szövődmények korai felismerése és adekvát kezelése a sikeres allogén őssejtátültetés sarkalatos pontja. Gyermekkorban az eljárás gyakorlata ráadásul nagyban különbözik a felnőttkorban alkalmazottól, melynek hátterében főként a nem malignus betegségek elérő klinikai megközelítése és a graft -versus-host betegség kisebb gyakorisága állnak [13].…”