Risk factors and outcomes of neutropenia following pediatric liver transplantation
Pamir Isik1, Burcu Belen Apak1, Lale Olcay1, Figen Ozcay2, Oya Balci Sezer2, Emre Karakaya3, Adem Safak3, Ayse Yavuz Derman4, Mehmet A. Haberal3.
1Pediatric Hematology and Oncology, Baskent University, Ankara, Turkey; 2Department of Pediatric Gastroenterology, Baskent University, Ankara, Turkey; 3Department of General Surgery, Division of Transplantation, Baskent University, Ankara, Turkey; 4Department of Biostatistics, Baskent University, Ankara, Turkey
Introduction: Solid organ transplantation (SOT) is an ideal therapeutic option for patients with end-stage organ dysfunction, enhancing both survival and quality of life. However, post-transplant neutropenia has been associated with increased rates of infection and acute rejection. This single-center retrospective study aimed to determine the frequency of neutropenia within the first year following pediatric liver transplantation, identify associated risk factors, and analyze the relationships between neutropenia development and clinical outcomes such as graft rejection and infection.
Materials and Methods: Data from 47 pediatric patients (5 months to 17,5 years old) who developed neutropenia (defined as absolute neutrophil count <1000/mm3) within the first year after liver transplantation at Başkent University Ankara Hospital Solid Organ Transplantion Center between September 2015 and January 2024 were retrospectively evaluated from medical records and computerized records.
Results: The average age of patients at the time of transplantation was 4.92 ± 4.93 years, with 63.83% being male. Pre-transplant cytomegalovirus (CMV) seropositivity was observed in 68.09% of recipients and 95.45% of donors. Additionally, 54.35% of recipients and 85.71% of donors had a history of pre-transplant Epstein-Barr virus (EBV) infection. During the neutropenic period, 40.43% of patients received a sepsis diagnosis. Other common risk factors for the development of neutropenia were immunosuppressive drug effect (36.17% in recipients), CMV infection (8.51%). Intravenous antibiotics were administered to 59.5% of patients, while 4.26% received oral antibiotics. Supportive therapies included granulocyte colony-stimulating factor (G-CSF) in 34.04%, intravenous immunoglobulin (IVIG) in 6.38%, and granulocyte suspension in 6.38% of patients. Invasive fungal infection occurred in 14.89% of patients post-neutropenia, and sepsis was observed in 21.28%. Complete recovery from neutropenia was seen in 80.43% of patients. Within the first year, 21,7% (n=10) experienced acute rejection, all of which resolved completely. Chronic rejection developed in only 2 patients. Patients were categorized into two groups based on neutrophil levels (500-1000/mm3 and <500/mm3), with the former showing significantly higher rates of sepsis, usage of intravenous antibiotics, G-CSF, IVIG and granulocyte suspension transfusion compared to the latter (p<0.05). Univariate logistic regression analysis revealed that a one-unit increase in C-reactive protein reduced neutrophil levels (500-1000/mm3 range) by 0.99 times (p=0.027, OR=0.990, %95 CI: 0.982 – 0.999). Furthermore, a 0.59 times decrease in neutrophil levels correlated with a one-unit increase in hospitalization within the first year post-transplant (p=0.0004, OR=0.585, %95 CI: 0.407 – 0.841).
Conclusion: This study identified infection and the use of immunosuppressive drugs, inherent to the SOT process, as the most significant etiological factors in the development of post-SOT neutropenia. To prevent neutropenia that may predispose patients to complications such as invasive fungal infection and sepsis, close monitoring of immunosuppressive drug use and effective infection control in post-transplant patients is essential.
[1] Neutropenia; Liver transplantation; Pediatrics