Pediatric patients treated for acute lymphoblastic leukemia (ALL) with allogeneic hematopoietic stem cell transplantation (HSCT) from unrelated donors, compared with sibling donors, showed higher risk for infection, according to results published in the American Journal of Hematology.

The study was supplementary to the multicenter, international ALL-SCT-BFM 2003 trial (ClinicalTrials.gov Identifier: NCT01423500) that included 432 children and adolescents with ALL. Patients received total body irradiation (TBI)-based myeloablative HSCT.

Transplantations came from either human leukocyte antigen-matched sibling donors (MSD; 129 patients) or matched unrelated donors (MUD; 303 patients). Patients received cyclosporine A as graft-versus-host-disease (GVHD) prophylaxis. With MUD-based HSCT, prophylactic treatment additionally included antithymocyte globulin (ATG), methotrexate, and leucovorin. Infections considered in this study were severe infections of grade 3 or higher.

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Six patients died prior to neutrophil engraftment. For patients who received MSD-based HSCT, median time to neutrophil engraftment was 18 days (range, 9-45). For those with MUD-based HSCT, this occurred in a median of 23 days (range, 8-108; P <.001).

Overall, 172 patients had 1 or more severe infections. Prior to 30 days post-HSCT, MUD-based, compared with MSD-based, transplantations showed a stronger relationship to overall infection risk (hazard ratio [HR], 2.57; P <.001). Between days 30 and 100 post-HSCT, the HR for this risk was 2.91 (P =.011).

Compared with patients receiving HSCT from MSD, patients with MUD-based HSCT experienced greater risks of different types of infections. Prior to 30 days post-HSCT, bacterial infections occurred more often (HR, 2.24; P =.041) for these patients, and they also showed a nonsignificant trend of more fungal infections during this period (HR, 4.06; P =.057).

Viral infections were more common prior to 30 days post-HSCT (HR, 2.66; P =.007) for patients who received MUD-based HSCT compared with patients who received MSD-based HSCT. Between 30 and 100 days post-HSCT, the HR for this risk rose to 3.89 (P =.002).

On its own, chronic GVHD posed an infection risk beyond 100 days post-HSCT (HR, 2.57; P =.002).

Infection risks more often affected patients receiving transplants from MUD. “This could be explained by an intensified GVHD prophylaxis consisting of serotherapy with ATG and administration of methotrexate for recipients of MUD transplants,” noted the study authors.

Reference

1.     Pichler H, Lawitschka A, Glogova E, et al. Allogeneic hematopoietic stem cell transplantation from unrelated donors is associated with higher infection rates in children with acute lymphoblastic leukemia – A prospective international multicenter trial on behalf of the BFM-SG and the EBMT-PDWP [published online May 16, 2019]. Am J Hematol. doi:10.1002/ajh.25511