Evaluation of frequency, clinic, risk factors, treatment and monitoring of CMV infection in patients with bone marrow transplantation

Background: Infection is one of the most important factors affecting morbidity and mortality after bone marrow transplantation (BMT). Although infectious complications are mostly caused by bacterial agents in patients undergoing BMT, cytomegalovirus (CMV) infection is the most common viral infection. CMV leads to additional pathologies such as pneumonia, gastroenteritis, encephalitis, hepatitis, retinitis, pancytopenia and causes severe morbidity and mortality in these patients. Aim: The aim of this study was to evaluate the frequency, clinical findings, risk factors, treatment and follow-up of CMV infection in pediatric patients hospitalized in our BMT center and to improve the follow-up and treatment of the patients to be followed up in our BMT center. Materials and Methods: The follow-up files of patients who underwent BMT between January 2008 and February 2018 were evaluated retrospectively. Age, gender, malignant / benign disease group, type of BMT, preparation regimen, engrafman times, prophylaxis applied, pre-transplant CMV serology of the donor, CMV diagnostic method, CMV serology status after transplantation, day of CMV positivity, CMV treatment complications of BMT, survival after BMT and causes of death were evaluated. SPSS 24.0 program was used for statistical analysis Results: One of the 70 patients who underwent BMT in our center had been transplanted twice. Twenty (28.6%) of the patients were female, 50 (71.4%) were male, and the median age of BMT was 11.1 years (8 months-17 years). Sixty (85.7%) of the diagnoses were malignant and 10 (14.3%) were benign. Twenty one (51.6%) patients were ALL, 9 (15%) were AML, 13 (21.6%) were solid tumors and 7 (11.6%) were lymphoma. In the benign disease group, 3 (30%) were primary immunodeficiencies and 7 (70%) were bone marrow deficiencies. Sixteen (22.8%) of the transplants were autologous and 54 (77.2%) were allogeneic transplantations. All of the allogeneic transplants were HLA compatible donors. Stem cell source was bone marrow in 50 (71.4%) and peripheral blood in 20 (28.6%). The preparation regimens were all myeloablative; total body irradiation was applied to 28 (40%) patients. The most commonly used regimen was TVI-VP (35.7%), BU-VP-MEL (12.8%) and BU-CY-MEL (11.4%). The mean neutrophil engraftment day was 17.3 ± 4.3; mean platelet engraftment day was 23.7 ± 12.9; mean absolute lymphocyte count time of (ALC) 100 µl was 10.2 ± 3.5 days; mean time of ALC 500 µl was 27.4 ± 21.2 days. CMV infection was detected in 30 (42.8%) patients and CMV disease (pneumonia and hepatitis) in 2 (2.8%) patients. CMV diagnosis was based on pp65 antigenemia in 8 (11.4%), PCR in 19 (27.1%), pp65 and PCR in 43 (61.4%). There was no significant correlation between PCR and pp65 antigenemia results. When posttransplant CMV was detected, 14 (43.8%) of the patients were at day 0-30, 13 (40%) at day 30-100, 5 (15.6%) > at day 100. Thirty patients (93.8%) were treated with preemptive treatment and 2 patients (6.2%) were treated with treatment dosage. Fourteen patients (42.4%) received ganciclovir, 7 (21.2%) valganciclovir, 10 (30.3%) ganciclovir-IVIG, and 2 (6.1%) valganciclovir-IVIG treatments. Five of the patients were treated with ganciclovir and 1 of the patients was treated with valganciclovir who developed second CMV reactivation; there was no statistically significant difference in development of infection groups between the different treatment. The mean second CMV reactivation time was 111.1 ± 48.4 days. There was no statistically significant difference between CMV positive and CMV negative patients in terms of gender, age, engraftment times, fungal infection and recipient-donor CMV Ig G serology. TVI administration, using bone marrow as stem cell source, performing allogeneic transplantation, and development of graft-versus-host disease were found to be risk factors for CMV infection. CMV-related mortality was not detected in any of the patients; CMV positive and negative patients had similar survival rates for the first 100 days and 2 years after BMT. Conclusions: CMV infection is common in the first 100 days in patients who had BMT. The risk increases especially in patients who received myeloablative therapy with TVI, underwent allogeneic BMT, used bone marrow as a stem cell source and developed graft-versus-host disease. Early diagnosis and effective treatment reduces morbidity and mortality, so the follow-up of the patients should be done carefully.