Flow Cytometric Detection of Liposomes in the CSF of Patients with NHL/ALL, Treated with Intrathecal Liposomal Cytarabine: Synonymous of Toxicity?

Abstract

ObjectivesPatients with aggressive non-Hodgkin’s lymphoma (NHL) and acute lymphoblastic leukemia (ALL) with high risk of CNS infiltration or recurrence may receive prophylaxis or be treated with intrathecal injections (IT) of liposomal cytarabine (LC) once every 2 weeks (due to its sustained release of cytarabine).Sequential flow cytometric studies in patients with CNS involvement and treated with LC, allow to detect tumor cells as well as LC liposomes (LCL) in the CSF. The true meaning of the presence of these liposomes during the treatment with LC is still unknown.Patients and MethodsIn this study, we aimed to investigate the presence of LCL detected by Flow Cytrometry (FC) among 166 CSF samples of 69 patients treated with LC. Samples were taken before each administration of intrathecal LC and centrally processed.ResultsResults are shown in the below table. Abstract 5444. Table 1Patients with NHL/ALL, treated with Intrathecal Liposomal CytarabineNPatients69Samples166Liposomal Cytarabine Liposomes (LCL) in CSFN%Patients1319%DLBCL646%LLT215%ALL215%MCL18%MM18%CLL18%Samples2616%Males862%2616%Age66 years[33-84]LCL in CSF of patients receiving Liposomal CytarabinePROPHYLAXISNToxycityTotal nº of IT LC dosesPatients7nº of IT LC doses*3 (2-5).LCL7After 1st dose5After 2nd dose21 LLT patient: arachnoiditis, high intrathecal pressure, papillitis, without sequelae5After 3rd dose2After 5th dose1LCL in CSF of patients receiving Liposomal Cytarabine leptomeningeal disease TREATMENTNTumor: ToxycityTotal nº of IT LC dosesPatients6nº of IT LC doses*6 (4-7)LCL6After 1st dose31 DLBCL patient: Headache, dizziness and instability51 MM patient: Headache, dizziness and instability4After 3rd dose2After 5th dose11 ALL patient: Headache, dizziness and instability7* Median [range]The thirteen patients were simultaneously treated with LC and IT + IV dexamethasone. It was found no relationship between the amount of LCL and toxicity.Conclusions:Presence of LCL in CSF is detected in 15-20% of patients receiving IT LC as prophylaxis / treatment and it does not show a direct relationship with presence of toxicity.Although the true clinical significance of the presence of LCL in CSF remains unknown, their monitoring could be useful to individualize the treatment with CL IT (dose and time between doses). DisclosuresOff Label Use: Liposomal cytarabine is not approved for prophylaxys of lymphomatous meningitis..