Clinical utility of procalcitonin in bacterial infections in patients undergoing hematopoietic stem cell transplantation.

Am J Blood Res 2020;10(6):339-344 www.AJBlood.us /ISSN:2160-1992/AJBR0113274 Original Article Clinical utility of procalcitonin in bacterial infections in patients undergoing hematopoietic stem cell transplantation Amit Bansal1, Preethi Jeyaraman2, S K Gupta1, Nitin Dayal3, Rahul Naithani2 Pharmaceutical Sciences and Research University, New Delhi, India; 2Division of Hematology and Bone Marrow Transplant, Max Super-Speciality Hospital, Saket, New Delhi, India; 3Department of Lab Medicine, Max SuperSpeciality Hospital, Saket, New Delhi, India 1 Received April 25, 2020; Accepted December 1, 2020; Epub December 15, 2020; Published December 30, 2020 Abstract: Background: Infections are major contributor to morbidity and mortality in patients undergoing bone marrow transplant (BMT). Objective: To assess role of serum procalcitonin (PCT) as a useful biomarker for the infections and outcomes in these patients. Methods: Retrospective observational study. Results: Total 47 patients with febrile episodes were enrolled. Twenty patients underwent autologous BMT and 27 underwent allogeneic BMT. Bacterial infections were documented in 18/47 (38%) patients. Forty patients were neutropenic. The median fever duration was 10 days (range 3-30 days) in positive procalcitonin level group whereas it was 4 days (range 1-18) in negative group. This was statistically significant (P=0.000). Procalcitonin levels were high in 8/9 episodes of sepsis (P=0.029). Intensive care unit transfers and death were significantly higher in PCT positive group as compared to PCT negative group. Conclusion: Serum procalcitonin levels provide prognostic information of worse outcome in patients undergoing HSCT. Keywords: Bone marrow transplant, infection, procalcitonin Introduction Infectious complications remain a major concern for morbidity and mortality in patients with febrile neutropenic after hematopoietic stem cell transplant (HSCT) [1, 2]. Fever is, therefore, frequently treated with antimicrobial agents [3]. However, fever can occur with several transplant-related complications beside infectious diseases, such as drug infusion, acute graft versus host disease (GVHD) or engraftment syndrome [4, 5]. Conventionally blood and urine cultures have been employed to diagnose infections. However, yield of these cultures is not very high. We have earlier documented that exact cause of fever could be identified in only 50% of patients undergoing ASCT for multiple myeloma [6]. Turnaround time for culture reports to be available is also high given the clinical situation at hand. Unnecessary use of broad-spectrum antibiotic treatment harbors the risk of evolution of drug resistant bacteria and prolonged hospitalization [7]. Therefore, a marker that could help us differentiate infective fever vs others will be useful. Procalcitonin (PCT) is the propeptide of calcitonin devoid of hormonal activity and is normally produced during systemic infection in response to circulating microbial toxins and host inflammatory mediators in the C cells of the thyroid gland. Levels of PCT are undetectable (<0.1 ng/ml) in healthy individuals and small to modest increases (<1.5 ng/ml) are seen in viral infections and in non-infectious inflammatory responses. Procalcitonin has a long half-life of (25-30 hours) [8]. U.S. Food and Drug Administration (FDA) has approved PCT for use in conjunction with clinical assessment and other laboratory findings to assist in the risk assessment of critically sick people for progression to severe sepsis and septic shock [9]. High PCT levels at admission to the intensive care unit (ICU) were found to be a better predic- Procalcitonin in HSCT tor of mortality. Many studies have demonstrated that serum PCT levels are increased in patients with sepsis, and the high levels of PCT correlate with the outcome of the disease [9, 10]. PCT can be used for differential diagnosis, prognosis, and follow-up of critically sick patients [11]. Serum PCT levels have been noted to increase with increasing severity of sepsis. In addition, a rising PCT level might be used as an indicator that an infectious process is not under control and that better source control is required [12]. rooms with reverse barrier nursing. All persons entering the room used shoe covers, put on a face mask and cap, and washed their hands thoroughly or used antiseptic hand wash antimicrobial prophylaxis. All patients received oral ciprofloxacin, fluconazole and valacyclovir as antibacterial, antifungal and antiviral prophylaxis, respectively. Fluconazole and valacyclovir were stopped on day 28. Cotrimoxazole prophylaxis was not used after HSC infusion. However, there is limited data on usefulness of PCT in neutropenic population more so in patients who are undergoing HSCT. Only few studies are available regarding utility of procalcitonin in patients undergoing HSCT [1, 2, 13-16]. Majority of studies had small sample sizes and data were not sufficient for meaningful inclusion in clinical algorithms. In India, bone marrow transplant activity is increasing [17]. Therefore, its more relevant now that we have more studies on infections in HSCTs in India. Fever was defined as a single temperature of ≥101 F or >100.4 F lasting for more than 1 hour. Any febrile episode was treated with broad-spectrum antibiotics. When febrile episodes occurred, blood and urine cultures or clinical sample as indicated like pus culture or swab were sent. First-line antibiotic cover during conditioning consisted of piperacillin-tazobactam or cefoperazone-sulbactum and amikacin. This was modified later depending on microbiological information or clinical evolution. If fever persisted for 5 days or more empirical antifungal treatment with amphotericin B was started. For each episode of fever, we took measurement of PCT within 24 hour from the onset of fever. Any value >0.5 ng/ml was taken as positive. Patients were divided in two 2 groups depending on procalcitonin values: patients with even a single positive PCT report and patients with all negative PCT reports. Patients and methods It is a retrospective observational study designed to ascertain role of serum procalcitonin as a useful biomarker for the infections and outcomes in patients who underwent hematopoietic stem cell transplantation. The study protocol (AB/MPH/2016/002; Version 1.1) was approved by the Institutional Review Board (IRB). Inclusion criteria Patients undergoing hematopoietic stem cell transplant with even a single febrile episode in our institute from April 2012 to September 2014 were included in the study. All episodes till patients were in pre-engraftment phase were included. Exclusion criteria Patients with no febrile episode were excluded from the study. Similarly patients with febrile episodes where procalcitonin levels were not assessed were excluded. Febrile episodes after engraftment were excluded. Supportive care during transplant Patients were nursed in HEPA filtered air-conditioned sing (...truncated)