Blood Stream Infection Is Frequent during Conditioning but Does Not Impact Allogeneic Transplant Outcomes in the Modern Era

Introduction: Bacteremia occurs frequently in the neutropenic period of early allogeneic stem cell transplantation (SCT). Effective strategies have been developed for the rapid diagnosis and management of bacteremia in immunocompromised SCT recipients.  We analyzed the incidence of bacteremia during TBI-based myeloablative SCT to determine the impact on morbidity and mortality in a recent cohort of patients.

Methods: We studied outcomes in a cohort of 105 consecutive ex vivo T cell depleted (TCD) allogeneic transplants from 6/6 HLA-matched sibling donors between 2006–2014. Prophylactic antibiotics were not administered. Blood stream infection (BSI) was defined as the isolation of bacteria from any blood culture in a four week window (between days -8 to +21) during the initial hospitalization. All patients had hematologic malignancies and received myeloablative conditioning with fludarabine (125 mg/m2), age-adapted fractionated TBI and cyclophosphamide (120 mg/kg). Fractionated TBI was delivered at a total dose of 1200cGy (with lung shielding to 600cGy for subjects age <55 years) or 400-600cGy for subjects age ≥55 years. All subjects were managed as inpatients with prompt empiric broad spectrum antibiotics at the first onset of a neutropenic fever.

Results:Successful neutrophil recovery occurred in all subjects and the median time to ANC ≥500/uL was 13 days. Out of 105 subjects, 71 (67.5%) had a BSI and 63% occurred between days 0 to +7. Bacterial species isolated from the blood were classified according to their probable site of origin as oral/cutaneous gram-positive organisms (32%), other sites (mostly gram-negative) (34%), or mixed (34%). Organisms classified as oral/cutaneous were most frequently Streptococcus (44%) or Staphylococcus (43%) species while E. coli (36%), Klebsiella (27%) and Enterococci (18%) were the most common isolates classified as from other sites. One patient (<1%) succumbed to neutropenic polymicrobial septic shock on day+7. The occurrence of BSI was not predicted by pre-transplant factors such as age, gender, type of underlying malignancy or TBI dose. Even in the subgroup with oral/cutaneous organisms, BSI was unrelated to the intensity of oral mucositis (p= 0.16). There was no association between BSI and early outcomes such as the duration of initial hospitalization (p=0.70), requirement for total parenteral nutrition (TPN) (p=0.38), duration of TPN(p=0.49) or transfer to the intensive care Unit (p=0.34).  In addition, BSI exerted no statistically significant impact on delayed outcomes such as non-relapse mortality (p=0.6)  or overall survival (p=0.5).

Conclusion: Early BSI is common duringTBI-based conditioning, with a peak incidence between days 0 and 7, and is not associated with conditioning intensity or presence of oral mucositis. With optimal management, BSI does not impact short or long-term outcomes in allogeneic SCT recipients.