title: The CSF IL-10 concentration is an effective diagnostic marker in immunocompetent primary CNS lymphoma and a potential prognostic biomarker in treatment-responsive patients.
abstract: We aimed to confirm the diagnostic value and to evaluate the pre- and post-therapeutic prognostic value of cerebrospinal fluid (CSF) concentrations of interleukin (IL)-10 and IL-6 in patients with diffuse large B-cell primary central nervous system lymphoma (PCNSL).
  
  
  
  IL-10 and IL-6 concentrations were measured in 79 patients with PCNSL at diagnosis and in 40 control individuals. Fifty-four PCNSL patients underwent repeat assessments starting at diagnosis.
  
  
  
  The IL-10 concentration distinguished PCNSL from other neurologic diseases with a sensitivity of 88.6% and a specificity of 88.9% with a cutoff of 4 pg/ml. In a multivariate analysis of PCNSL patients, CSF involvement was associated with a higher IL-10 concentration (mean log (IL-10) of 4.4 versus 2.5 pg/ml, respectively, p = 0.0004). The pre-therapeutic IL-10 concentration had no prognostic impact on outcome. The IL-10 concentration decreased after treatment for most patients tested. Among patients with complete remission or partial remission, as evaluated by magnetic resonance imaging (MRI), a persistent detectable IL-10 level in the CSF at the end of treatment was associated with a negative impact on progression-free survival (PFS) (1-year PFS: 15%, 95% confidence interval [CI]: 2.5-38% versus 59%, 95% CI: 32-78%, respectively, p = 0.0004).
  
  
  
  Our study confirmed that IL-10 is a useful biomarker for the diagnosis of PCNSL. We highlight new findings showing that the IL-10 level in the CSF could be used as a surrogate marker for CSF involvement and that the post-treatment IL-10 concentration could complement standard MRI for therapeutic response assessment in PCNSL.
authors.affiliation: Groupe Hospitalier Pitié-Salpétrière, Neuro-oncology, Paris, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Nguyen-Them
authors.affiliation: Groupe Hospitalier Pitié-Salpétrière, Biological Hematology, Paris, France; Paris University Sorbonne UPMC, INSERM UMRS 1138, France.
authors.forename: Myrto
authors.initials: M
authors.lastname: Costopoulos
authors.affiliation: Groupe Hospitalier Pitié-Salpétrière, Biostatistics, Paris, France.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Tanguy
authors.affiliation: Groupe Hospitalier Pitié-Salpétrière, Neuro-oncology, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Houillier
authors.affiliation: Groupe Hospitalier Pitié-Salpétrière, Hematology, Paris, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Choquet
authors.affiliation: Hôpital René Huguenin, Institut Curie, Biological Hematology, Saint-Cloud, France.
authors.forename: Hind
authors.initials: H
authors.lastname: Benanni
authors.affiliation: Hôpital René Huguenin, Institut Curie, Hematology, Saint-Cloud, France.
authors.forename: Rwaida
authors.initials: R
authors.lastname: Elias-Shamieh
authors.affiliation: Groupe Hospitalier Pitié-Salpétrière, Biological Hematology, Paris, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Armand
authors.affiliation: Groupe Hospitalier Pitié-Salpétrière, Neuro-oncology, Paris, France.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Faivre
authors.affiliation: Hôpital René Huguenin, Institut Curie, Hematology, Saint-Cloud, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Glaisner
authors.affiliation: Hôpital René Huguenin, Institut Curie, Hematology, Saint-Cloud, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Malak
authors.affiliation: Hôpital René Huguenin, Institut Curie, Hematology, Saint-Cloud, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Vargaftig
authors.affiliation: Groupe Hospitalier Pitié-Salpétrière, Neuro-oncology, Paris, France; Paris University Sorbonne UPMC, INSERM U1127, CNRS UMR 7225, IHU, ICM, France.
authors.forename: Khê
authors.initials: K
authors.lastname: Hoang-Xuan
authors.affiliation: Hôpitaux Civils de Colmar, Neurology, Colmar, France.
authors.forename: Guido
authors.initials: G
authors.lastname: Ahle
authors.affiliation: Groupe Hospitalier Pitié-Salpétrière, Ophthalmology, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Touitou
authors.affiliation: Hôpital Claudius Regaud, Institut Curie, Ophthalmology, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cassoux
authors.affiliation: Groupe Hospitalier Pitié-Salpétrière, Biological Hematology, Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Davi
authors.affiliation: Groupe Hospitalier Pitié-Salpétrière, Biological Hematology, Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Merle-Béral
authors.affiliation: Groupe Hospitalier Pitié-Salpétrière, Biological Hematology, Paris, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Le Garff-Tavernier
authors.affiliation: Hôpital René Huguenin, Institut Curie, Hematology, Saint-Cloud, France; Collège de France, INSERM U1050, CNRS UMR 7241, Paris, France. Electronic address: carole.soussain@curie.fr.
authors.forename: Carole
authors.initials: C
authors.lastname: Soussain
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000134:cerebrospinal fluid*; D016022:Case-Control Studies; D016543:Central Nervous System Neoplasms / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000134:cerebrospinal fluid*; D015850:Interleukin-6 / Q000134:cerebrospinal fluid; D016015:Logistic Models; D008228:Lymphoma, Non-Hodgkin; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016753:Interleukin-10
keywords: Biomarker; Cerebrospinal fluid; IL-10; IL-10:IL-6 ratio; Primary CNS lymphoma; Response assessment