Objectives

Patients 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 Methods

In 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.

Results

Results are shown in the below table.

Abstract 5444. Table 1

Patients with NHL/ALL, treated with Intrathecal Liposomal Cytarabine

N
Patients 69  
Samples 166  
Liposomal Cytarabine Liposomes (LCL) in CSF 
 N %  
Patients 13 19%  
DLBCL 6 46%  
LLT 2 15%  
ALL 2 15%  
MCL 1 8%  
MM 1 8%  
CLL 1 8%  
Samples 26 16%  
Males 8 62%  
 26 16%  
Age 66 years [33-84]  
LCL in CSF of patients receiving Liposomal CytarabinePROPHYLAXIS 
 N Toxycity Total nº of IT LC doses 
Patients 7   
nº of IT LC doses* 3 (2-5).   
LCL 7   
After 1st dose 5   
After 2nd dose 2 1 LLT patient: arachnoiditis, high intrathecal pressure, papillitis, without sequelae 5 
After 3rd dose 2   
After 5th dose 1   
LCL in CSF of patients receiving Liposomal Cytarabine leptomeningeal disease TREATMENT 
 N Tumor: Toxycity Total nº of IT LC doses 
Patients 6   
nº of IT LC doses* 6 (4-7)   
LCL 6   
After 1st dose 3 1 DLBCL patient: Headache, dizziness and instability 5 
  1 MM patient: Headache, dizziness and instability 4 
After 3rd dose 2   
After 5th dose 1 1 ALL patient: Headache, dizziness and instability 7 
* Median [range] 
N
Patients 69  
Samples 166  
Liposomal Cytarabine Liposomes (LCL) in CSF 
 N %  
Patients 13 19%  
DLBCL 6 46%  
LLT 2 15%  
ALL 2 15%  
MCL 1 8%  
MM 1 8%  
CLL 1 8%  
Samples 26 16%  
Males 8 62%  
 26 16%  
Age 66 years [33-84]  
LCL in CSF of patients receiving Liposomal CytarabinePROPHYLAXIS 
 N Toxycity Total nº of IT LC doses 
Patients 7   
nº of IT LC doses* 3 (2-5).   
LCL 7   
After 1st dose 5   
After 2nd dose 2 1 LLT patient: arachnoiditis, high intrathecal pressure, papillitis, without sequelae 5 
After 3rd dose 2   
After 5th dose 1   
LCL in CSF of patients receiving Liposomal Cytarabine leptomeningeal disease TREATMENT 
 N Tumor: Toxycity Total nº of IT LC doses 
Patients 6   
nº of IT LC doses* 6 (4-7)   
LCL 6   
After 1st dose 3 1 DLBCL patient: Headache, dizziness and instability 5 
  1 MM patient: Headache, dizziness and instability 4 
After 3rd dose 2   
After 5th dose 1 1 ALL patient: Headache, dizziness and instability 7 
* Median [range] 
View Large

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).

Disclosures

Off Label Use: Liposomal cytarabine is not approved for prophylaxys of lymphomatous meningitis..

Topics:
cerebrospinal fluid, colony-stimulating factors, cytarabine, liposomes, toxic effect, dizziness, headache, diffuse large b-cell lymphoma, acute lymphocytic leukemia, arachnoiditis

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2014 by The American Society of Hematology
2014
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