A Randomized Clinical Trial Evaluating Lactiplantibacillus Plantarum for the Prevention of GI aGvHD: A Report From the Children's Oncology Group (ACCL1633).

Gastrointestinal (GI) acute graft-versus-host disease (aGvHD) is a leading cause of non-relapse mortality following allogeneic hematopoietic cell transplant (alloHCT). Previous studies have suggested that the intestinal microbiome may influence the risk of GI aGvHD. We performed a Phase 3, randomized, placebo-controlled clinical trial to examine the effect of L. plantarum 299v (LBP 299v) in preventing GI aGvHD. Participants (N = 161 evaluable participants) received LBP 299v or placebo from the start of conditioning therapy to 56 days post alloHCT (D56). Blood, stool, and clinical data were collected until 120 days post-transplant (D120). The D120 cumulative incidences of stages 1-4 GI aGvHD were 16% and 15% (P = .54), and overall grades 2-4 aGvHD were 26% and 29% (P = .95), LBP 299v and placebo groups, respectively. No patients developed L. plantarum bacteremia and no difference in serious adverse events was reported (P = 1.00). Administration of LBP 299v was associated with increased microbial diversity at D0 (P = .02) and reduced mucosal barrier injury at D7 (P = .02). Microbial signatures significantly differed between the groups; however, this was not associated with the investigated clinical outcomes. We conclude that administration of LBP 299v is safe among children and adolescents undergoing alloHCT but ineffective at preventing GI aGvHD.