Invasive Atypical Mycobacterial Infection in Allogeneic Pediatric HSCT

Abstract

<h3>Introduction</h3> Infection is a major cause of morbidity and mortality following hematopoietic stem cell transplant (HSCT). Atypical or nontuberculous mycobacterial (NTM) infections are known to occur at higher rates in patients with a compromised immune system and a study by Unal et al. reported a 6.4% incidence of NTM infections in pediatric allogeneic HSCT recipients. Disease severity with NTM infections is broad and can range from asymptomatic line infections to disseminated disease. Antimicrobial therapies for NTM infections are variable and typically multiagent. Limited data are available describing the impact of these infections and their associated therapies on HSCT outcomes in children. <h3>Methods</h3> We retrospectively reviewed outcomes for pediatric allogeneic HSCT recipients between 2014 and 2019 whose courses were complicated by symptomatic invasive NTM infection. Metrics analyzed include underlying disease, conditioning regimen, antimicrobial therapies, survival and donor engraftment. <h3>Results</h3> 5 patients were diagnosed and started on multidrug therapy for NTM surrounding HSCT. Presenting symptoms for each patient are described in Figure 1. Patient demographics and NTM details are shown in Table 1. All 5 patients received myeloablative conditioning (MAC) with busulfan and fludarabine, in addition to thiotepa (n=1), ATG (n=1) and alemtuzumab (n=1) in select patients. All patents engrafted ≤ 20 days with at least 99% donor chimerism. Patient 3 showed mixed chimerism on day 25, eventually resulting in graft loss requiring re-transplantation. Four out of five patients (80%) are alive today with median follow up time of 4.3 years (range 3.4 – 5.3 years). <h3>Conclusion</h3> Our experience suggests that children undergoing HSCT complicated by NTM infections have favorable outcomes. NTM directed multi-drug therapy was well tolerated and did not immediately appear to affect engraftment. Recurrence of symptomatic invasive NTM infection occurred in two patients post-HSCT after stopping NTM therapy, while a third patient developed a first-time symptomatic invasive NTM infection after HSCT. This observation advocates for continuation of antimicrobial therapy through immune reconstitution.