Graft-versus-host disease causes enteric bacterial BSI in children after HCT

Acute gastrointestinal graft-versus-host disease is likely to cause greater enteric bacterial bloodstream infection density in children who have had allogeneic hematopoietic cell transplantation, according to research published in Clinical Infectious Diseases.

“There remains a paucity of literature documenting that patients with [acute gastrointestinal graft-versus-host disease (aG-GVHD)] are, in fact, at increased risk for enteric bacteremia,” Prakash Satwani, MD, of the Mailman School of Public Health, Columbia University, and colleagues wrote. “The idea that the mucosal barrier injury and disruption of commensal bacteria found in aG-GVHD facilitate bacterial seeding of the bloodstream is still being investigated.”

The researchers conducted a retrospective study of 264 patients (mean age, 9 years) who received allogeneic hematopoietic cell transplantation (AlloHCT) at New York–Presbyterian Morgan Stanley Children’s Hospital between April 2000 and December 2012 for either malignant (61.4%) or nonmalignant disease (38.6%).

Within 100 days of AlloHCT, 45% of the patients developed grade II-IV acute GVHD (aGVHD). Of these, 64% had aG-GVHD and 36% had acute liver or skin GVHD. Fifty-one percent of those with aG-GVHD had grade II, 46% had grade III, and 3% had grade IV, according to Satwani and colleagues. The remaining 55% of patients did not develop aGVHD.

About 46% of patients had one or more episodes of enteric bacterial bloodstream infection (EB-BSI) density within 6 months of AlloHCT, the researchers said. Median time for aG-GVHD patients to develop EB-BSI was 75 days vs. 54 days for those without GVHD.

Patients with aG-GVHD had an EB-BSI density much higher than patients before the onset of aG-GVHD (2.26 vs. 0.95; P = .03), and higher than those who never developed aGVHD (2.26 vs. 1.58; P = .03).

The most common genera of organisms that caused EB-BSI were: Klebsiella spp. (22.3%), Enterobacter spp. (14.9%), Acinetobacter spp. (14%) and Enterococcus spp. (13.2%), the researchers wrote.

A majority of patients received tacrolimus and mycophenolate mofetil for aGVHD prophylaxis. Patients who developed grade II-IV aGVHD were treated with a tapering dose of methylprednisolone for up to 10 weeks. Prophylaxis for herpes simplex virus, fungal infections and cytomegalovirus also were administered.

According to the researchers, there were 66 cases of treatment-related mortality and 50 disease relapses in an average of 3.28 years.

“Our results support the theory that aG-GVHD predisposes patients to EB-BSI for a prolonged period of time,” they wrote. “Because of the high morbidity and mortality associated with EB-BSI, effective prevention strategies for patients with elevated risk of infection would be beneficial.

“Prophylactic agents such as probiotics should be studied prospectively in patients with aG-GVHD.” – by David Jwanier

Disclosure: The researchers report no relevant financial disclosures.