The Adverse Event Profile in Patients Treated with Transferon<sup>TM</sup> (Dialyzable Leukocyte Extracts): A Preliminary Report

Abstract

Background: Dialyzable leukocyte extracts (DLE) are heterogeneous mixtures of peptides less than 10 kDa in size that are used as immunomodulatory adjuvants in immune-mediated diseases. Transferon TM is DLE manufactured by National Polytechnic Institute (IPN), and is registered by Mexican health-regulatory authorities as an immunomodulatory drug and commercialized nationally. The proposed mechanism of action of Transferon TM is induction of a Th1 immunoregulatory response. Despite that it is widely used, to date there are no reports of adverse events related to the clinical safety of human DLE or Transferon TM. Objective: To assess the safety of Transferon TM in a large group of patients exposed to DLE as adjuvant treatment. Methods: We included in this study 3844 patients from our Clinical Immunology Service at the Unit of External Services and Clinical Research (USEIC), IPN. Analysis was performed from January 2014 to November 2014, searching for clinical adverse events in patients with immune-mediated diseases and treated with * Corresponding author. Transferon TM as an adjuvant. Results: In this work we observed clinical nonserious adverse events (AE) in 1.9% of patients treated with Transferon TM (MD 1.9, IQR 1.7-2.0). AE were 2.8 times more frequently observed in female than in male patients. The most common AE were headache in 15.7%, followed by rash in 11.4%, increased disease-related symptomatology in 10%, rhinorrhea in 7.1%, cough in 5.7%, and fatigue in 5.7% of patients with AE. 63% of adverse event presentation occurred from day 1 to day 4 of treatment with Transferon TM , and mean time resolution of adverse events was 14 days. In 23 cases, the therapy was stopped because of adverse events and no serious adverse events were observed in this study. Conclusion: Transferon TM induced low frequency of nonserious adverse events during adjuvant treatment. Further monitoring is advisable for different age and disease groups of patients.

Dialyzable Leukocyte Extract (Transferon™) Administration in Sepsis: Experience from a Single Referral Pediatric Intensive Care Unit

“…It is produced under Good Manufactoring Practice processes and facilities. Serious adverse events had not been reported and a recent safety assessment has confirmed that adverse events associated with Transferon™ are rare and nonserious [30]. Transferon™ has been approved by the Mexican drug regulatory agency (COFEPRIS) for human consumption as an immunomodulatory agent, and a robust biological assay has been developed to serve as a quality control, ensuring an adequate and measurable activity of Transferon™ [31].…”

Reactivación de micosis fungoide en estadio de placa por administración de extracto dializado de leucocitos vía oral. Reporte de cas

“…En 63 %, los EA se presentaron entre los días 1 y 4 del tratamiento y el tiempo de resolución fue de 14 días. 18 En el caso que describimos, y basados en la temporalidad, el posible EA fue la reactivación de las lesiones de MF, que se presentó antes de 48 horas del inicio del EDLH, y al igual que en el estudio mencionado, las lesiones remitieron antes de dos semanas al suspender el extracto.…”

Sequencing Analysis and Identification of the Primary Peptide Component of the Dialyzable Leukocyte Extract “Transferon Oral”: The Starting Point to Understand Its Mechanism of Action

“…“Transferon Oral” has been used as an auxiliary treatment in patients with inflammatory diseases ( Hernandez et al, 2013 ; Homber et al, 2015 ). “Transferon Oral” improves resolution of infectious diseases by increasing the number of systemic IFN-γ cells in ocular fungal keratitis and enhances the survival of pediatric patients with sepsis by lowering C reactive protein (CRP), rising increases total lymphocyte numbers and decreasing total neutrophil count ( Santacruz-Valdes et al, 2010 ; Castrejon Vazquez et al, 2019 ).…”