title: TNF-α increases in the CSF of children with acute lymphoblastic leukemia before CNS relapse.
abstract: There is scarce information regarding the concentration of cytokines in cerebrospinal fluid (CSF) of children with acute lymphoblastic leukemia (ALL) and their clinical association with CNS status. A prospective analysis of 40 patients <18years with newly diagnosed ALL was performed. Human cytokine magnetic bead panel assay values of IL-2, IL-4, IL-6, IL-8, IL-10, MCP-1, TNF-α in CSF at diagnosis, end of induction to remission, and 6months after diagnosis were determined. IL-6 and MCP-1 values showed a significant increment at the end of induction. From the whole group 4 (10.0%), patients relapsed to the CNS at a median of 11.48months. A significantly higher value of TNF-α at third determination in these CNS-relapsed patients was documented, 7.48 vs. 2.86pg/mL in 36 children without relapse (p=0.024). TNF-α concentration increased at a median 5.48months before CNS relapse. By receiver-operating characteristic curve (ROC) analysis, the best cut-off point of TNF-α concentration that better predicted CNS relapse was ≥1.79pg/mL. In conclusion an increase in TNF-α concentration on CSF preceded CNS relapse in children with ALL. An increase in MCP-1 and IL-6 was not associated to CNS relapse and appears to result from an inflammatory response after IT injection of chemotherapy.
authors.affiliation: Department of Hematology, Dr. José Eleuterio González University Hospital, School of Medicine, Universidad Autónoma de Nuevo León, Monterrey, Mexico. Electronic address: carjaime@hotmail.com.
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Jaime-Pérez
authors.affiliation: Department of Hematology, Dr. José Eleuterio González University Hospital, School of Medicine, Universidad Autónoma de Nuevo León, Monterrey, Mexico.
authors.forename: Carmen Magdalena
authors.initials: CM
authors.lastname: Gamboa-Alonso
authors.affiliation: Department of Hematology, Dr. José Eleuterio González University Hospital, School of Medicine, Universidad Autónoma de Nuevo León, Monterrey, Mexico.
authors.forename: Raúl Alberto
authors.initials: RA
authors.lastname: Jiménez-Castillo
authors.affiliation: Department of Hematology, Dr. José Eleuterio González University Hospital, School of Medicine, Universidad Autónoma de Nuevo León, Monterrey, Mexico.
authors.forename: Leslie Jazmín
authors.initials: LJ
authors.lastname: López-Silva
authors.affiliation: Department of Hematology, Dr. José Eleuterio González University Hospital, School of Medicine, Universidad Autónoma de Nuevo León, Monterrey, Mexico.
authors.forename: Mónica Andrea
authors.initials: MA
authors.lastname: Pinzón-Uresti
authors.affiliation: Department of Hematology, Dr. José Eleuterio González University Hospital, School of Medicine, Universidad Autónoma de Nuevo León, Monterrey, Mexico.
authors.forename: Andrés
authors.initials: A
authors.lastname: Gómez-De León
authors.affiliation: Department of Hematology, Dr. José Eleuterio González University Hospital, School of Medicine, Universidad Autónoma de Nuevo León, Monterrey, Mexico.
authors.forename: David
authors.initials: D
authors.lastname: Gómez-Almaguer
mesh_terms: D000293:Adolescent; D016543:Central Nervous System Neoplasms / Q000175:diagnosis* / Q000209:etiology; D018932:Chemokine CCL2 / Q000134:cerebrospinal fluid; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D007223:Infant; D015850:Interleukin-6 / Q000134:cerebrospinal fluid; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000134:cerebrospinal fluid* / Q000150:complications / Q000473:pathology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D012008:Recurrence; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid*
chemical_list: D018932:Chemokine CCL2; D016207:Cytokines; C508600:IL6 protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha
keywords: ALL relapse; Acute lymphoblastic leukemia (ALL); Central nervous system (CNS); Cytokines; Interleukins