Abstract
BackgroudEstablishing diagnostic and prognostic biomarkers of primary central nervous system lymphoma (PCNSL) is a challenge. This study evaluated the value of dynamic interleukin (IL)-10 cerebrospinal fluid (CSF) concentrations for prognosis and relapse prediction in PCNSL.MethodsConsecutive 40 patients newly diagnosed with PCNSL between April 2015 and April 2019 were recruited, and serial CSF specimens were collected by lumbar punctures (LP) or by Ommaya reservoir at diagnosis, treatment, and follow-up phase.ResultsWe confirmed that an elevated IL-10 cutoff value of 8.2 pg/mL for the diagnosis value of PCNSL showed a sensitivity of 85%. A persistent detectable CSF IL-10 level at the end of treatment was associated with poor progression-free survival (PFS) (836 vs. 481 days, p = 0.049). Within a median follow-up of 13.6 (2–55) months, 24 patients relapsed. IL-10 relapse was defined as a positive conversion in patients with undetectable IL-10 or an increased concentration compared to the last test in patients with sustained IL-10. IL-10 relapse was detected a median of 67 days (28–402 days) earlier than disease relapse in 10/16 patients.ConclusionThis study highlights a new perspective that CSF IL-10 relapse could be a surrogate marker for disease relapse and detected earlier than conventional magnetic resonance imaging (MRI) scan. Further evaluation of IL-10 monitoring in PCNSL follow-up is warranted.
Highlights
Primary central nervous system lymphoma (PCNSL) is a rare extranodal subtype of non-Hodgkin lymphoma (NHL) that accounts for 4% of newly diagnosed brain tumors and 4 to 6% of all extra-nodal lymphomas, with an incidence of 0.4–0.5/100,000 per year [1]
IL-10 may play various roles in the development of lymphoma and high levels of serum IL-10 were associated with poor prognosis in Diffused large B cell lymphoma (DLBCL); IL-10 and IL-10 receptors were identified as novel treatment targets [5,6,7,8,9]
In 2013, Rubenstein and colleagues reported that the bivariate elevation of IL-10 and chemokine (C-X-C motif) ligand 13 (CXCL 13) in Cerebrospinal fluid (CSF) is highly specific for PCNSL, with a positive predictive value of 95% and a negative predictive value of 88% [11]
Summary
Primary central nervous system lymphoma (PCNSL) is a rare extranodal subtype of non-Hodgkin lymphoma (NHL) that accounts for 4% of newly diagnosed brain tumors and 4 to 6% of all extra-nodal lymphomas, with an incidence of 0.4–0.5/100,000 per year [1]. The sensitivity and specificity of CSF IL-10 for diagnosing PCNSL varies across studies. In 2013, Rubenstein and colleagues reported that the bivariate elevation of IL-10 and chemokine (C-X-C motif) ligand 13 (CXCL 13) in CSF is highly specific for PCNSL, with a positive predictive value of 95% and a negative predictive value of 88% [11]. In primary vitreoretinal lymphoma (PVRL), a special subtype of PCNSL, the diagnostic value of the anterior chamber fluid IL-10 concentration and IL-10/IL-6 ratio has been well documented [13, 14]
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