Liposomal cytarabine for treatment of myeloid central nervous system relapse in chronic myeloid leukaemia occurring during imatinib therapy.
BACKGROUND
Central nervous system (CNS) relapse in chronic myeloid leukaemia (CML) is rare and if recorded is usually found to occur in patients with lymphoblastic transformation. The BCR/ABL tyrosine kinase inhibitor imatinib is highly effective in patients with CML, but hardly crosses the blood-brain barrier.


METHODS
We report on two CML patients who developed a myeloid CNS relapse during treatment with imatinib. One patient was in major cytogenetic response at the time of CNS relapse. In both cases, the myeloid origin of neoplastic cells in the cerebrospinal fluid (CSF) was demonstrable by immunophenotyping, and their leukaemic origin by detection of the BCR/ABL oncoprotein. No BCR/ABL kinase domain mutations were found. Both patients received intrathecal liposomal cytarabine (50 mg each cycle; 6 cycles). In one patient, additional CNS radiation was performed, whereas in the other, consecutive treatment with dasatinib (70 mg per os twice daily) was started.


RESULTS
In response to therapy, the clinical symptoms resolved, and the leukaemic cells in the CSF disappeared in both cases. After three months of observation, both patients are in complete cytogenetic and major molecular response, without evidence for a systemic or a CNS relapse.


CONCLUSIONS
'Anatomic' resistance against imatinib in the CNS can lead to a myeloid CNS relapse. Liposomal cytarabine with or without radiation is effective as local therapy in these patients. For systemic treatment and prophylaxis, BCR/ABL kinase inhibitors crossing the blood-brain barrier such as dasatinib should be considered in patients with CNS relapse.
Aichberger
K J
KJ
Medical University of Vienna, Austria.
Herndlhofer
S
S
Agis
H
H
Sperr
W R
WR
Esterbauer
H
H
Rabitsch
W
W
Knöbl
P
P
Haas
O A
OA
Thalhammer
R
R
Schwarzinger
I
I
Sillaber
C
C
Jäger
U
U
Valent
P
P
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001549:Benzamides; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000556:secondary; D003561:Cytarabine / Q000008:administration & dosage* / Q000627:therapeutic use*; D000069439:Dasatinib; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use; D013844:Thiazoles / Q000627:therapeutic use; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D001549:Benzamides; D008081:Liposomes; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D003561:Cytarabine; D000068877:Imatinib Mesylate; D000069439:Dasatinib