Infection surveyance in patients with pediatric hematopoetic stem cell transplantation

Introduction: Hematopoietic stem cell transplantation (HSCT) is an effective treatment for the treatment of many malignant and non-malignant diseases in children and adolescents. Early and late complications after hematopoietic stem cell transplantation affect the prognosis of the disease and life quality of the patients. Post-transplant infections are an important cause of morbidity and mortality and prolong hospital stay. Bacterial infection, invasive fungal infection (IFI) and cytomegalovirus (CMV) viremia /reactivation are common in patients undergoing hematopoietic stem cell transplantation. The most common infections are catheter-related primary bloodstream infections, pneumonia and urinary tract infection. Type of underlying disease, genetic polymorphisms and different conditioning regimens affect the profile of infections in theese patients. Other related factors, such as central venous catheters (CVC), presence of comorbidity, intensity and duration of neutropenia, use of mucositis and antimicrobial prophylaxis may affect the occurence of infection complications. It is known that CVC-related infections in cancer patients are associated with a seven-fold increase in mortality in this population. Morbidity and mortality rates increase due to infection after transplantation. Recent advances in supportive care, improved understanding of the mechanisms of immunosuppression, reduced intensity preparation regimens used with new antimicrobial drugs and prophylaxis strategies reduced morbidity and mortality. Hematopoietic stem cell transplantation is carried out in Turkey since 1992. However, few studies have examined the specific infection characteristics and complications in children and adolescents in our country. Objective: The aim of this retrospective study is to determine the infectious agents, clinical findings and prognosis of hematopoietic stem cell transplant patients in Children's Hospital of Ege University Faculty of Medicine and to evaluate the effect of stem cell transplantation complications on mortality and morbidity within the first 100 days after transplantation. Hypothesis: In patients undergoing hematopoietic stem cell transplantation, infections affect the development of early complications. Secondary hypothesis, graft versus host disease (GVHD) and immunosuppressive regimens used for transplantation increase the frequency of posttransplant opportunistic infections. Methods: The first 100 days after transplantation of 200 allogeneic and autologous HSCT patients in the Bone Marrow Transplantation Unit of Ege University Faculty of Medicine, Department of Pediatrics (AD) between September 2014 and December 2018 were included in the study. The data was gathered from clinic follow-up files and electronic hospital records. Patient age during transplantation, stem cell source used, information about the donor, properties of the given conditioning regimen, GVHD prophylaxis, donor-recipient CMV serological status, pre and post-transplant bacterial infection, presence of CMV and fungal infection, antifungal, antibacterial and antiviral prophylaxis, neutrophil engraftment days, posttransplant steroid use; when infection was detected, infection site, diagnosis, method used for diagnose of infection, casue of infection, blood hemogram and biochemical parameters, pre-transplant post-transplant peak CMV DNA and EBV DNA levels, mortality in the first 100 days after transplantation, and in case of mortality, the cause were recorded in the case report form. We excluded patients that vital data could not be reached. Results: 115 (57.5%) of the patients were male and 85 (42.5%) were female. Mean age was 94.3 months and median 85 months (2-252). During follow-up, 14 patients underwent a second stem cell transplantation due to graft rejection / failure. Allogeneic stem cell transplantation was performed in 187 patients and autologous stem cell transplantation was performed in 13 patients. TBI was applied to 33 patients within the preparation regimen. GVHD prophylaxis was given to 182 patients. Neutrophil engraftment day was 17.5 days, median 17 days (9-32). Neutrophil engraftment day could not be mentioned in 7 patients since neutrophil counts were always 1000 / μl after transplantation. There was no engraftment in 17 patients due to graft rejection / failure and 8 patients died. After transplantation, 13 patients out of 200 had no febrile attacks. 187 patients had 323 febrile attacks. After transplantation, 172 of 323 febrile attacks were defined as fever of unknown origin. Of the 151 bacterial febrile attacks, 66 were gram positive and 85 were gram negative. Ganciclovir was used in 90 patients due to CMV development after transplantation. After transplantation, IFI developed in 21 patients. The development of CMV reactivation after transplantation does not increase the risk for IFI (P = 0.799). After transplantation, viral respiratory infection was detected in 40 patients, the most common agent was rhinovirus. Viral gastroenteritis infection was detected in 44 patients, most commonly agent was rotavirus. Urine BK virus infection was detected in 25 patients after transplantation. Acute GVHD developed in 54 patients. The risk of bacterial infection and CMV development increases in patients with aGVHD after transplantation (P = 0.002, 0.014, respectively). There was no statistically significant relationship between IFI development after transplantation and aGVHD (P = 0.864). Although CMV reactivation was more common in patients with steroid use after transplantation, it was not statistically significant (P = 0.58). There was no significant relationship between the risk of IFI development after steroid use after transplantation. (P = 0.101). The risk of developing bacterial infection increases in patients with steroid use before febrile attacks (P = <0.001). There was no significant relationship between conditioning regimens and bacterial infection, CMV development and IFI risk (P = 0.111, 0.175, 0.138, respectively). Bacterial infection after transplantation of stem cell source was not statistically significant between CMV development and IFI development (P = 0.088, 0.499, 0.143, respectively). Bacterial infection and shock development were statistically significant (P = 0.001). Bacterial infection and ICU stay were statistically significant (P = 0.003). 9% mortality was observed in the first 100 days after transplantation. Discussion: Bacterial infection was detected 43.5% of heterogeneous group of patients who underwent HSCT using different preparation regimen, donor and stem cell source with different indications in childhood when we evaluated after HSCT. The risk of bacterial infection and CMV development increased in patients with acute GVHD. The risk of developing bacterial infections was increased in patients with steroid use after transplantation. Intensive care hospitalization rate was 24.1% in cases of bacterial infection. Infection-related mortality was found in 13 (6.5%) patients who underwent HSCT in childhood. Keywords: Hematopoietic stem cell transplantation, Bacterial infection, CMV viremia, CMV reactivation, Invasive fungal infection, Graft Versus Host Disease, Mortality