THE SAFETY OF LIPOSOMAL CYTARABINE IN CENTRAL NERVOUS SYSTEM INFILTRATION BY HAEMATOLOGIC MALIGNANCIES
(Abstract release date: 05/18/17)
EHA Library. García Ramírez P. 05/18/17; 182443; PB1729
Patricia García Ramírez
Contributions
Contributions
Abstract
Abstract: PB1729
Type: Publication Only
Background
Central nervous system (CNS) involvement, both leptomeningeal and parenchimatous conveys a poor prognostic in haematological malignancies. As well as systemic chemotherapy that crosses hematoencephalic barrier, intrathecal (IT) chemotherapy has become an attractive approach because of direct action in the cerebrospinal fluid (CSF). Liposomal cytarabine (Depocyte®) is a convenient formulation that maintains cytotoxic concentrations of cytarabine in CSF for an extended period of time (>14 days). This permits to decrease the frequency of lumbar punctures, without losing efficacy and minimizing the patient´s discomfort.
Aims
The objective of this retrospective, observational study is to evaluate the efficacy and safety of liposomal cytarabine in patients with CNS infiltration by haematological malignancies.
Methods
36 consecutive patients with haematological disease and risk of CNS infiltration underwent flow cytometry (FC) analysis of CSF in a single center from December 2014 to December 2016. CNS involvement was assessed by using standard CSF cytology, 8-color flow cytometry or MRI imaging. Along with systemic therapy, all patients considered positive were treated 50 mg of IT Liposomal cytarabine administered by lumbar puncture every 2 weeks for 4 doses and every 4 weeks thereafter. Concomitant dexamethasone for arachnoiditis prophylaxis was added both i.v. and IT. We analysed the rate of adverse events (AE) and the time for CSF clearance. Short follow up precluded assessment of cumulative incidence of CNS relapse/progression.
Results
Data from 36 patients were analysed. A total of nine patients were considered to have CSF involvement, all of them detected by FC. Of note, all of them were considered negative for CSF infiltration by standard cytology. Three additional patients received IT therapy as prophylaxis since MRI imaging showed brain involvement by the malignancy. The median age of this 12 patients was 52 years (range16-69), 58.3% were female. Diagnosis were B-cell lymphoproliferative disorder 41.7% (CLL, Burkitt, DLBCL), ALL 25%, AML 25% and multiple myeloma 8.3%.
The median number of doses per patient was 6.5 (SD 1.7). CSF clearance was achieved after a median of 1 dose (range 1-3) or 20 days (range 16-86). Overall rate of CNS response was 100%. Two patients (16.7%) had leptomenigeal relapse during the IT treatment.
The overall AE incidence was 66.7%. The most common AE include: headache, peripheral sensory neuropathy, back pain and nausea. Severe neurotoxicity has been encountered in four patients: cauda equina syndrome (2), encephalitis (1) and arachnoiditis (1). Treatment had to be discontinued in 3 patients because of side effects but this did not lead to relapse. The median time to AE occurrence was 6 cycles (range 4-7) or 110 days (range 33-227). The incidence and severity of AE seemed to increase with the cumulative number of cycles administered. In most patients neurological complications resolved or improved with time.
Conclusion
use of liposomal formulation of cytarabine for IT administration has become an effective option for the treatment of leptomeningeal involvement by haematological malignancies. Neurological AE are reversible; however, they accumulate and worsen with time, thus precluding long-term use.
Session topic: 20. Aggressive Non-Hodgkin lymphoma - Clinical
Keyword(s): toxicity, flow cytometry, CNS, Ara-C (cytarabine)
Abstract: PB1729
Type: Publication Only
Background
Central nervous system (CNS) involvement, both leptomeningeal and parenchimatous conveys a poor prognostic in haematological malignancies. As well as systemic chemotherapy that crosses hematoencephalic barrier, intrathecal (IT) chemotherapy has become an attractive approach because of direct action in the cerebrospinal fluid (CSF). Liposomal cytarabine (Depocyte®) is a convenient formulation that maintains cytotoxic concentrations of cytarabine in CSF for an extended period of time (>14 days). This permits to decrease the frequency of lumbar punctures, without losing efficacy and minimizing the patient´s discomfort.
Aims
The objective of this retrospective, observational study is to evaluate the efficacy and safety of liposomal cytarabine in patients with CNS infiltration by haematological malignancies.
Methods
36 consecutive patients with haematological disease and risk of CNS infiltration underwent flow cytometry (FC) analysis of CSF in a single center from December 2014 to December 2016. CNS involvement was assessed by using standard CSF cytology, 8-color flow cytometry or MRI imaging. Along with systemic therapy, all patients considered positive were treated 50 mg of IT Liposomal cytarabine administered by lumbar puncture every 2 weeks for 4 doses and every 4 weeks thereafter. Concomitant dexamethasone for arachnoiditis prophylaxis was added both i.v. and IT. We analysed the rate of adverse events (AE) and the time for CSF clearance. Short follow up precluded assessment of cumulative incidence of CNS relapse/progression.
Results
Data from 36 patients were analysed. A total of nine patients were considered to have CSF involvement, all of them detected by FC. Of note, all of them were considered negative for CSF infiltration by standard cytology. Three additional patients received IT therapy as prophylaxis since MRI imaging showed brain involvement by the malignancy. The median age of this 12 patients was 52 years (range16-69), 58.3% were female. Diagnosis were B-cell lymphoproliferative disorder 41.7% (CLL, Burkitt, DLBCL), ALL 25%, AML 25% and multiple myeloma 8.3%.
The median number of doses per patient was 6.5 (SD 1.7). CSF clearance was achieved after a median of 1 dose (range 1-3) or 20 days (range 16-86). Overall rate of CNS response was 100%. Two patients (16.7%) had leptomenigeal relapse during the IT treatment.
The overall AE incidence was 66.7%. The most common AE include: headache, peripheral sensory neuropathy, back pain and nausea. Severe neurotoxicity has been encountered in four patients: cauda equina syndrome (2), encephalitis (1) and arachnoiditis (1). Treatment had to be discontinued in 3 patients because of side effects but this did not lead to relapse. The median time to AE occurrence was 6 cycles (range 4-7) or 110 days (range 33-227). The incidence and severity of AE seemed to increase with the cumulative number of cycles administered. In most patients neurological complications resolved or improved with time.
Conclusion
use of liposomal formulation of cytarabine for IT administration has become an effective option for the treatment of leptomeningeal involvement by haematological malignancies. Neurological AE are reversible; however, they accumulate and worsen with time, thus precluding long-term use.
Session topic: 20. Aggressive Non-Hodgkin lymphoma - Clinical
Keyword(s): toxicity, flow cytometry, CNS, Ara-C (cytarabine)
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