Collaborations with Cancer Control (Table 3):
Infectious complications are common post-HCT due to prolonged neutropenia, mucosal barrier damage, and extended treatment with immunosuppressive drugs. Two recent COG trials attempted to decrease infectious complications, but unfortunately were unsuccessful. ACCL0934 randomized patients undergoing HCT to receive levofloxacin prophylaxis (n=210) or no prophylaxis (n=214) from two days prior to HCT until neutrophil recovery. Levofloxacin was not toxic, but bacteremia rates were not significantly different between the levofloxacin and no prophylaxis groups (11% vs 17%, p=0.06).33 ACCL1131 randomized patients to either caspofungin (n=144) or a triazole (n=146) as anti-fungal prophylaxis from the day of stem cell infusion until day 42 post-HCT or hospital discharge, whichever occurred first. The trial was powered to determine if caspofungin reduced the rate of proven or probable invasive fungal disease (IFD) by day 42 post-HCT from 7% to 2% compared to triazole . A planned interim analysis after 290 patients enrolled found very low rates of IFD in both cohorts (1.4% vs 1.4%, p=0.99), resulting in the study’s early closure.34 An embedded ancillary study evaluated serial beta-D-glucan (BDG) as a screening test for IFD in 51 patients. All 25 positive results were false positives, thus serial BDG monitoring is not a useful screening tool for IFD in pediatric HCT.35
ACCL1633: Despite improvements in donor selection and GVHD prophylaxis strategies, grade II-IV acute GVHD occurs in approximately 40% of pediatric recipients of allogeneic HCT.36, 37Several studies have linked changes in gastrointestinal (GI) microbial dysbiosis to transplant outcomes, including GVHD.38Interventions that preserve or restore normal microbiota may reduce GI-associated toxicity and GVHD. ACCL1633 randomized HCT recipients to either oral Lactobacillus plantarum or placebo for 8 weeks. An interim analysis after the first 128 patients found no differences in the incidence of GI GVHD (unpublished data) and the study was closed for futility. Laboratory studies that utilize banked serial stool and blood samples to correlate the GI microbiome and serum biomarkers with clinical outcomes are currently ongoing.