The Adverse Event Profile in Patients Treated with TransferonTM (Dialyzable Leukocyte Extracts): A Preliminary Report
Toni Homberg1, Violeta Sáenz2, Jorge Galicia-Carreón2, Iván Lara2, Edgar Cervantes-Trujano1,2, Maria C. Andaluz1,2, Erika Vera1, Oscar Pineda1, Julio Ayala-Balboa1, Alejandro Estrada-García3, Sergio Estrada-Parra3, Mayra Pérez-Tapia4, Maria C. Jiménez-Martínez5*
1Clinical Trials Branch and Clinical Immunology Service, Unit of External Services and Clinical Research (USEIC), National School of Biological Sciences, National Polytechnic Institute, Mexico City, Mexico.
2Unit of Pharmacovigilance, Unit of External Services and Clinical Research (USEIC), National School of Biological Sciences, National Polytechnic Institute, Mexico City, Mexico.
3Department of Immunology, National School of Biological Sciences, National Polytechnic Institute, Mexico City, Mexico.
4Unit of R&D in Bioprocesses (UDIBI), National School of Biological Sciences, National Poly-technic Institute, Mexico City, Mexico.
5Department of Biochemistry, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.
DOI: 10.4236/pp.2015.62009   PDF   HTML   XML   4,543 Downloads   5,977 Views   Citations


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. TransferonTM 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 TransferonTM 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 TransferonTM. Objective: To assess the safety of TransferonTM 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 TransferonTM as an adjuvant. Results: In this work we observed clinical nonserious adverse events (AE) in 1.9% of patients treated with TransferonTM (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 TransferonTM, 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: TransferonTM induced low frequency of nonserious adverse events during adjuvant treatment. Further monitoring is advisable for different age and disease groups of patients.

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Homberg, T. , Sáenz, V. , Galicia-Carreón, J. , Lara, I. , Cervantes-Trujano, E. , Andaluz, M. , Vera, E. , Pineda, O. , Ayala-Balboa, J. , Estrada-García, A. , Estrada-Parra, S. , Pérez-Tapia, M. and Jiménez-Martínez, M. (2015) The Adverse Event Profile in Patients Treated with TransferonTM (Dialyzable Leukocyte Extracts): A Preliminary Report. Pharmacology & Pharmacy, 6, 65-74. doi: 10.4236/pp.2015.62009.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Medina-Rivero, E., Merchand-Reyes, G., Pavón, L., Vázquez-Leyva, S., Pérez-Sánchez, G., Salinas-Jazmín, N., Estrada-Parra, S., Velasco-Velázquez, M. and Pérez-Tapia, S.M. (2014) Batch-to-Batch Reproducibility of TransferonTM. Journal of Pharmaceutical and Biomedical Analysis, 88, 289-294.
[2] Navarro Cruz, D., Serrano Miranda, E., Orea, M., Estrada Parra, S., Teran-Ortiz, L., Gomez-Vera, J. and Flores-Sandoval, G. (1996) Transfer Factor in Moderate and Severe Atopic Dermatitis. Revista Alergia México, 43, 116-123.
[3] Byston, J., Cech, K., Pekarek, J. and Jilkova, J. (1996) Effect of Anti-Herpes Specific Transfer Factor. Biotherapy, 9, 73-75.
[4] Masi, M., De Vinci, C. and Baricordi, O.R. (1996) Transfer Factor in Chronic Mucocutaneous Candidiasis. Biotherapy, 9, 97-103.
[5] Viza, D., Fudenberg, H.H., Palareti, A., Ablashi, D., De Vinci, C. and Pizza, G. (2013) Transfer Factor: An Overlooked Potential for the Prevention And Treatment of Infectious Diseases. Folia Biologica (Prague), 59, 53–67.
[6] Berron-Perez, R., Chavez-Sanchez, R., Estrada-Garcia, I., Espinosa-Padilla, S., Cortez-Gomez, R., Serrano-Miranda, E., Ondarza-Aguilera, R., Perez-Tapia, M., Pineda Olvera, B., Jimenez-Martinez, M.C., Portugues, A., Rodriguez, A., Cano, L., Pacheco, P.U., Barrientos, J., Chacon, R., Serafin, J., Mendez, P., Monges, A., Cervantes, E. and Estrada-Parra, S. (2007) Indications Usage, and Dosage of the Transfer Factor. Revista Alergia México, 54, 134–139.
[7] García-Hernández, U., Robledo-Avila, F.H., Alvarez-Jiménez, V.D., Rodríguez-Cortés, O., Wong-Baeza, I., Serafín-López, J., Aguilar-Anguiano, L.M., Estrada-Parra, S., Estrada-García, I., Pérez-Tapia, S.M. and Chacón-Salinas, R. (2014) Dialyzable Leukocyte Extracts Activate TLR-2 on Monocytes. Natural Product Communications, 9, 853-856.
[8] Herlin, T., Jensen, J.R., Thestrup-Pedersen, K. and Zachariae, H. (1981) Dialyzable Leukocyte Extract Stimulates cAMP in T Gamma Lymphocytes. Allergy, 36, 337-343.
[9] Tsuneta, H. (1984) The Role of Cultured Thymic Epithelium and Dialyzable Leukocyte Extracts on the Maturation Process of T Cell. Study of Their Effects on Cyclic Nucleotides Levels in Thymocytes. Hokkaido Igaku Zasshi, 59, 128-139.
[10] Franco-Molina, M.A., Mendoza-Gamboa, E., Castillo-Leon, L., Tamez-Guerra, R.S. and Rodriguez-Padilla, C. (2005) Bovine Dialyzable Leukocyte Extract Modulates the Nitric Oxide and Pro-Inflammatory Cytokine Production in Lipopolysaccharide-Stimulated Murine Peritoneal Macrophages in Vitro. Journal of Medicinal Food, 8, 20-26.
[11] Hernandez, M.E., Mendieta, D., Pérez-Tapia, M., Bojalil, R., Estrada-Garcia, I., Estrada-Parra, S. and Pavon, L. (2013) Effect of Selective Serotonin Reuptake Inhibitors and Immunomodulator on Cytokines Levels: An Alternative Therapy for Patients with Major Depressive Disorder. Clinical and Developmental Immunology, Article ID: 267871.
[12] Estrada-Parra, S., Nagaya, A., Serrano, E., Rodriguez, O., Santamaria, V., Ondarza, R., Chavez, R., Correa, B., Monges, A., Cabeza, R., Calva, C. and Estrada-Garcia, I. (1998) Comparative Study of Transfer Factor and Acyclovir in the Treatment of Herpes Zoster. International Journal of Immunopharmacology, 20, 521-535.
[13] Luna-Baca, G.A., Linares, M., Santacruz-Valdes, C., Aguilar-Velazquez, G., Chavez, R., Perez-Tapia, M., Estrada-Garcia, I., Estrada-Parra, S. and Jimenez-Martinez, M.C. (2007) Immunological Study of Patients with Herpetic Stromal Keratitis Treated with Dialyzable Leukocyte Extracts. 13th International Congress of Immunology-ICI, Proceedings Immunology, Rio de Janeiro, 21-25 August 2007, 67-70.
[14] Kirkpatrick, C.H. and Smith, T.K. (1976) The Nature of Transfer Factor and Its Clinical Efficacy in the Management of Cutaneous Disorders. Journal of Investigative Dermatology, 67, 425-430.
[15] Nekam, K., Kalmar, L., Gergely, P., Kelemen, G., Fekete, B., Lang, I., Levai, J. and Petranyi, G.Y. (1977) In Vitro Effect of Transfer Factor on Active Rosettes and Leucocyte Migration of Patients with Cancer. Clinical & Experimental Immunology, 27, 416-420.
[16] Mexican Official Standard NOM-220-SSA1-2012, Installation and Operation of Pharmacovigilance.
[17] US Department of Health and Human Services Food and Drug Administration, Office of the Commissioner, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research, Center for Devices and Radiological Health, Office of Good Clinical Practice (2009) Guidance for Clinical Investigators, Sponsors, and IRBs Adverse Event Reporting to IRBs—Improving Human Subject Protection.
[18] Reviewed on Line (2014).
[19] Copaxone Product Monograph (2011).
[20] Johnson, K.P., Brooks, B.R., Cohen, J.A., Ford, C.C., Goldstein, J., Lisak, R.P., Myers, L.W., Panitch, H.S., Rose, J.W., Schiffer, R.B., Vollmer, T., Weiner, L.P. and Wolinsky, J.S. (1998) Extended Use of Glatiramer Acetate (Copaxone) Is Well Tolerated and Maintains Its Clinical Effect on Multiple Sclerosis Relapse Rate and Degree of Disability. Copolymer 1 Multiple Sclerosis Study Group. Neurology, 50, 701-708.
[21] Bornstein, M.B., Miller, A., Slagle, S., Weitzman, M., Crystal, H., Drexler, E., Keilson, M., Merriam, A., Wassertheil-Smoller, S., Spada, V., et al. (1987) A Pilot Trial of COP 1 in Exacerbating-Remitting Multiple Sclerosis. The New England Journal of Medicine, 317, 408-414.
[22] Tran, C.L., Knowles, S.R., Liu, B.A. and Shear, N.H. (1998) Gender Differences in Adverse Drug Reactions. Journal of Clinical Pharmacology, 38, 1003-1009.
[23] Pistone, G., Gurreri, R., Alaimo, R., Curiale, S. and Bongiorno, M.R. (2014) Gender Differences in Adverse Drug Reactions in Dermatological Patients in West Sicily: An Epidemiological Study. Journal of Dermatolog Treat, 25, 510-512.
[24] Murray, H.W. (1994) Interferon-Gamma and Host Antimicrobial Defense: Current and Future Clinical Applications. The American Journal of Medicine, 97, 459-467.
[25] Gallin, J.L., Farber, J.M., Holland, S.M. and Nutman, T.B. (1995) Interferon-γ in the Management of Infectious Diseases. Annals of Internal Medicine, 123, 216-224.
[26] Hübel, K.K., Dale, D.C. and Liles, W.C. (2002) Therapeutic Use of Cytokines to Modulate Phagocyte Function for the Treatment of Infectious Diseases: Current Status of Granulocyte Colony-Stimulating Factor, Granulocyte-Macrophage Colony-Stimulating factor, macrophage Colony-Stimulating Factor, and Interferon-γ. The Joural of Infectious Diseases, 185, 1490-1501.
[27] Birk, S., Kruuse, C., Petersen, K.A.T., Felt-Hansen, P. and Olesen, J. (2006) The Headache-Inducing Effect of Cilostazol in Human Volunteers. Cephalalgia, 26, 1304-1309.
[28] DeSantana, J.M. and Sluka, K.A. (2008) Central Mechanisms in the Maintenance of Chronic Widespread Noninflammatory Muscle Pain. Current Pain and Headache Reports, 12, 338-343.
[29] Guo, S., Olesen, J. and Ashina, M. (2014) Phosphodiesterase 3 Inhibitor Cilostazol Induces Migraine-Like Attacks via Cyclic AMP Increase. Brain, 137, 2951-2959.
[30] Schmidt, B.M., Kusma, M., Feuring, M., Timmer, W.E., Neuhäuser, M., Bethke, T., Stuck, B.A., Hörmann, K. and Wehling, M. (2001) The Phosphodiesterase 4 Inhibitor Roflumilast Is Effective in the Treatment of Allergic Rhinitis. Journal of Allergy and Clinical Immunology, 108, 530-536.
[31] Lee, R.J., Chen, B., Doghramji, L., Adappa, N.D., Palmer, J.N., Kennedy, D.W. and Cohen, N.A. (2013) Vasoactive Intestinal Peptide Regulates Sinonasal Mucociliary Clearance and Synergizes with Histamine in Stimulating Sinonasal Fluid Secretion. The FASEB Joural, 27, 5094-103.
[32] Kolbeck, R.C. and Speir, W.A. (1991) Theophylline, Fatigue, and Diaphragm Contractility: Cellular Levels of 45Ca and cAMP. Journal of Applied Physiology, 70, 1933-1937.
[33] Staines, D.R. (2006) Phosphodiesterase Inhibitors May Be Indicated in the Treatment of Postulated Vasoactive Neuropeptide Autoimmune Fatigue-Related Disorders. Medical Hypotheses, 66, 203-204.
[34] Staines, D.R., Brenu, E.W. and Marshall-Gradisnik, S. (2009) Postulated Vasoactive Neuropeptide Immunopathology Affecting the Blood-Brain/Blood-Spinal Barrier in Certain Neuropsychiatric Fatigue-Related Conditions: A Role for Phosphodiesterase Inhibitors in Treatment? Neuropsychiatric Disease and Treatment, 5, 81-89.

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