Prolonged intrathecal chemotherapy replacing cranial irradiation in high-risk acute lymphatic leukaemia: long-term follow up with cerebral computed tomography scans and endocrinological studies.
Cranial irradiation in children with acute lymphatic leukaemia (ALL) decreases the risk of CNS relapse but is associated with serious long-term side-effects. We present the long-term outcome of 21 children with high-risk ALL who received prolonged intrathecal chemotherapy instead of the recommended cranial irradiation. Intrathecal triple therapy (methotrexate, hydrocortisone, and cytarabine) was administered every 2nd month throughout the maintenance phase. The average number of courses of intrathecal methotrexate was 8.7 and of triple 9.0. The 5-year event-free survival was 79%. No CNS relapses occurred. CT scan was performed at diagnosis, at cessation of therapy, and 3 years thereafter. No density abnormalities, pathological contrast enhancement, ventricular dilatation, or calcifications were found. One child showed cortical atrophy both at diagnosis and at cessation of therapy. There was a slight decrease in height SDS with time but no change in weight SDS. Delayed bone age was found in 5 children. No abnormalities of growth hormone, thyroid, adrenal, or gonadal function were observed.


CONCLUSIONS
The study indicates that extended intrathecal chemotherapy in children with high-risk ALL may provide an effective protection from CNS relapses and is associated with a low risk of long-term side-effects.
Hasle
H
H
Department of Paediatrics, Odense University Hospital, Denmark.
Helgestad
J
J
Christensen
J K
JK
Jacobsen
B B
BB
Kamper
J
J
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D016371:Cranial Irradiation / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006128:Growth / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage; D007278:Injections, Spinal; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D010908:Pituitary Hormones, Anterior / Q000097:blood; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D013963:Thyroid Hormones / Q000097:blood; D014057:Tomography, X-Ray Computed
D010908:Pituitary Hormones, Anterior; D013963:Thyroid Hormones; D003561:Cytarabine; D006854:Hydrocortisone; D008727:Methotrexate