Azithromycin timing, duration does not affect hematologic relapse after pediatric HSCT
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SALT LAKE CITY — Early azithromycin use did not affect hematologic relapse among pediatric hematopoietic stem cell transplant recipients, according to study results.
Duration of azithromycin use also had no effect on these outcomes, findings of an 8-year review presented at Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR showed.
“Based on our findings, we think it is likely safe to use azithromycin in pediatric transplant recipients with hematologic malignancies outside of the engraftment period,” researcher Anthony Sabulski, MD, pediatric hematologist/oncologist at Cincinnati Children’s Hospital Medical Center, told Healio.
Background
Azithromycin is a macrolide antibiotic commonly used to treat atypical pneumonias.
It often is used as part of multiagent therapy for mycobacteria infections among HSCT recipients.
The agent also has immunomodulatory properties, and prior research has shown it can inhibit T-cell proliferation and alter T cell-mediated cytokine production, Sabulski said.
A study by Bergeron and colleagues showed prophylactic azithromycin beginning at the time of conditioning chemotherapy appeared associated with increased incidence of relapse and mortality, but three follow-up studies of adults showed no association between traditional azithromycin use and relapse or death.
“There have not been any follow-up studies in pediatric transplant recipients,” Sabulski said. “We felt it was important to study azithromycin use in this population to help guide treatment strategies and establish whether it is safe to use azithromycin in pediatric transplant recipients with hematologic malignancies.”
Methods
Sabulski and colleagues aimed to evaluate the effect of early azithromycin exposure on key outcomes among pediatric patients who underwent HSCT. They hypothesized that azithromycin use in the first year after HSCT would not impact release in this group.
Researchers documented azithromycin exposures among 703 pediatric patients (59% male) who underwent a combined 837 HSCTs at their institution from 2010 to 2018. Investigators performed chart reviews to obtain clinical data.
Median age at transplant was 6 years. The majority of patients (89.5%) were aged younger than 18 years at the time of HSCT, and more than half (60%) underwent HSCT for non-malignant disease. The most common malignancies in the cohort included acute myeloid leukemia, acute lymphoblastic leukemia and myelodysplastic syndrome.
Hematologic relapse and 1-year mortality served as primary outcomes.
Key findings
Researchers determined 25% of all patients had documented azithromycin exposure in the first year after HSCT, a number Sabulski said was higher than he anticipated.
Sabulski and colleagues assessed outcomes among the 168 patients with hematologic malignancies, 27% of whom received azithromycin within the first year after HSCT.
The most common indications for azithromycin use included respiratory tract infection (59%), anti-inflammatory agent (24%) and bacterial prophylaxis (7%).
Two-thirds (65%) of these patients received azithromycin for the first time within 150 days after transplant. Only two patients (4%) received azithromycin between day 0 and day 25, preventing researchers from making conclusions on peri-engraftment exposure.
Results showed no statistically significant differences in 1-year mortality rates between those who received azithromycin prior to day 100 after transplant (32%), between day 100 and day 365 (30%), or at any point during the first year after HSCT (30%) compared with those who received no azithromycin (25%).
Results showed no statistically significant differences in relapse rates among those who received azithromycin prior to day 100 (21%), between day 100 and day 365 (22%), or at any point during the first year after HSCT (22%) compared with those who received no azithromycin (36%).
Researchers also assessed the effect of azithromycin duration.
Results showed no significant differences in 1-year mortality rates between those with exposure of 30 days or less (36%) or more than 30 days (15.4%) compared with those who received no azithromycin (25%).
Similarly, results showed no significant difference in relapse rates among those with exposure of 30 days or less (27%) or more than 30 days (7.7%) compared with no azithromycin (36%).
Sabulski and colleagues then performed Cox regression analysis to compare relapse and 1-year mortality among patients with hematologic malignancies who received azithromycin in the first year after transplant with those who did not.
Results showed patients with hematologic malignancies who received azithromycin had a significantly higher risk for death (HR = 2.4; P = .009) at 1 year after HSCT compared with patients who did not receive azithromycin.
The same analysis showed no significant difference in hematologic relapse between groups.
“We think this increased risk [for] death reflects the clinical complications that merited azithromycin initiation in those patients,” Sabulski told Healio. “Similarly, the timing and duration of azithromycin use did not impact relapse or survival.”
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Sabulski A, et al. Abstract 22. Presented at: Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR; April 23-26, 2022; Salt Lake City.
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