SIGNIFICANCE OF ELEVATED LEVELS OF SOLUBLE FACTORS IN THE CEREBROSPINAL-FLUID IN PATIENTS WITH ADULT T-CELL LEUKEMIA

Although it has been recognized previously that several markers are pr esent in the cerebrospinal fluid (CSF), their clinical usefulness of t hese markers in the diagnosis of malignant lymphoma infiltrating to th e CNS has not yet been established. In order to determine their diagno stic usefulness as markers of meningeal infiltration by lymphoma cells in patients with adult T-cell leukemia (ATL), we measured some solubl e factors in the CSF of patients with ATL and non- ATL patients. Solub le CD4 (sCD4) was highly elevated in all patients with ATL and meninge al infiltration. The CSF level of the soluble interleukin-2 receptor ( sIL-2R; sCD25) was markedly elevated in 13 (72.2%) of 18 patients with ATL and meningeal infiltration. Levels of sCD4 and sCD25 in the CSF o f patients with ATL and meningeal infiltration were significantly high er than in non-ATL patients (p < .01 and p < .001, respectively). Thes e findings indicate that levels of sCD4 and sCD25 in the CSF are proba bly associated with meningeal infiltration by leukemia cells expressin g CD4 and CD25 on surface membranes. CSF levels of sCD4 in 14 (60.9%) of 23 ATL patients and sCD25 in 13 (72.2%) of 18 ATL patients without meningeal infiltration were moderately elevated. These findings sugges t that a small number of leukemic cells which were not detected by con ventional CSF examination may have infiltrated the meninges in these p atients. Sequential measurements of sCD4 and sCD25 in CSF obtained fro m patients with meningeal infiltration by leukemic cells showed that s CD4 and sCD25 levels reflected the activity of leukemic meningitis and correlated with the number of cells in CSF. However, the levels of sC D4 in CSF did not fall below the limit of detection even when the numb er of cells in CSF became normal. It is thought that the level of sCD4 in CSF is a more sensitive marker for detecting the infiltration of l eukemic cells in CSF than the number of cells present in the CSF consi dering the clinical course of two patients with acute type ATL. Theref ore, ATL patients with meningeal infiltration should receive treatment s until sCD4 levels become normal and not just until the number of cel ls become normal. Our results also suggest that measurement of CSF lev els of sCD4 and sCD25 is useful for the differential diagnosis of asep tic meningitis and meningeal infiltration by leukemic cells in patient s with smoldering ATL. We conclude that measurement of soluble factors in CSF plays an important role in diagnosis, prophylaxis and treatmen t of meningitis in patients with ATL.