Regional cerebral blood flow and neuron-specific enolase in cerebrospinal fluid in children with acute lymphoblastic leukemia during induction treatment.
OBJECTIVE
To investigate possible side effects on the central nervous system from intrathecal methotrexate given during induction treatment for acute lymphoblastic leukemia in childhood.


METHODS
Twenty-five children with acute lymphoblastic leukemia were examined by cerebral single photon emission computed tomography at the beginning of treatment (16 untreated, 9 during the first week) and after 4 weeks of treatment. Cerebrospinal fluid was sampled for analyses of neuron-specific enolase on four occasions in 54 patients.


RESULTS
Regional cerebral blood flow became impaired during treatment in all patients. The single photon emission computed tomography score for nonhomogeneous perfusion increased from 6.4/50 to 16.6/50. Hypoperfusion was global without any clear preference for any lobe. The cerebellum was not affected. Neuron-specific enolase increased significantly during treatment, with a peak after 1 week, followed by a gradual decrease, but it was still significantly elevated after 4 weeks.


CONCLUSIONS
Nonhomogeneous cerebral hypoperfusion was found in all patients during induction treatment, including repeated intrathecal administration of methotrexate, but before systemic high-dose methotrexate. Signs of neuronal injury, in the form of a moderate increase in neuron-specific enolase in the cerebrospinal fluid, were found early in the treatment. Follow-up is needed to evaluate the long-term impact of these findings.
Osterlundh
G
G
Department of Pediatrics, Göteborg University, Sweden.
Bjure
J
J
Lannering
B
B
Kjellmer
I
I
Uvebrant
P
P
Márky
I
I
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage; D001921:Brain / Q000098:blood supply* / Q000000981:diagnostic imaging; D002648:Child; D002675:Child, Preschool; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D010751:Phosphopyruvate Hydratase / Q000134:cerebrospinal fluid*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology*; D012039:Regional Blood Flow; D012074:Remission Induction; D015899:Tomography, Emission-Computed, Single-Photon; D014750:Vincristine / Q000008:administration & dosage
D014750:Vincristine; D004317:Doxorubicin; D001215:Asparaginase; D010751:Phosphopyruvate Hydratase; D008727:Methotrexate