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Mucositis not neutropenia determines bacteremia among hematopoietic stem cell transplant recipients
A H E Herbers1, A F J de Haan, W J F M van der Velden
1Department of Hematology, Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Background:
In the 1960s, it was reported that infectious complications were the main cause of fever during neutropenia that followed hematopoietic stem cell transplant (HSCT). More recently, mucositis has become recognized as an important determinant of the inflammatory response and infectious complications.
Methods:
The objective of this prospective study was to determine the impact of intestinal mucositis, as measured by plasma citrulline, and neutropenia on the systemic inflammatory response (C-reactive protein) and the occurrence of bacteremia among 2 cohorts of HSCT recipients: 1 composed of 18 patients who had been treated with a myeloablative (MA) regimen (high-dose melphalan) and the other involving 19 patients who had received the non-myeloablative (NMA) regimen (fludarabine and cyclophosphamide). Blood cultures were obtained for surveillance from admission onwards as well as at the onset of fever.
Results:
The MA regimen induced severe intestinal mucositis manifest by citrullinemia <10 μmol/L, which was accompanied by an inflammatory response, and bacteremia affected 8 (44%) of 18 patients and coincided with the nadir of citrullinemia. By contrast, those who had been treated with the NMA regimen did not develop severe intestinal mucositis, had a moderate inflammatory response, and only 2 (11%) of the 19 patients developed bacteremia. However, both groups experienced profound neutropenia and its duration was significantly longer for those receiving the NMA regimen.
Conclusion:
This study suggests that severe intestinal mucositis, i.e., citrullinemia <10 μmol/L, defines the period of risk of bacteremia better than does neutropenia, and that measuring plasma citrulline may prove useful in deciding who needs empirical antimicrobial therapy and when.
Insights
Severe intestinal mucositis, indicated by low plasma citrulline levels, is a better predictor of bacteremia risk after hematopoietic stem cell transplant (HSCT) than neutropenia. Measuring citrulline can guide antimicrobial therapy decisions.
Area of Science:
- Hematology
- Transplant Immunology
- Infectious Disease
Background:
- Infectious complications historically dominated fevers post-hematopoietic stem cell transplant (HSCT).
- Intestinal mucositis is now recognized as a key factor influencing inflammatory responses and infection risk following HSCT.
Purpose of the Study:
- To investigate the impact of intestinal mucositis and neutropenia on systemic inflammation and bacteremia.
- To compare outcomes between myeloablative (MA) and non-myeloablative (NMA) HSCT regimens regarding mucositis and bacteremia.
Main Methods:
- Prospective study of 2 HSCT cohorts (MA: n=18, NMA: n=19).
- Intestinal mucositis assessed via plasma citrulline levels.
- Systemic inflammation measured by C-reactive protein; bacteremia monitored through blood cultures.
Main Results:
- Myeloablative (MA) regimen induced severe mucositis (citrulline <10 μmol/L), leading to bacteremia in 44% of patients.
- Non-myeloablative (NMA) regimen resulted in less severe mucositis, with bacteremia in only 11% of patients.
- Both groups experienced neutropenia, but it was prolonged in the NMA group.
Conclusions:
- Severe intestinal mucositis (citrulline <10 μmol/L) is a more precise indicator of bacteremia risk than neutropenia post-HSCT.
- Plasma citrulline levels may aid in determining the need and timing for empirical antimicrobial therapy in HSCT patients.
