Acute lymphoblastic leukemia is the most common
malignancy in children. All current
therapy regimens used in the treatment of childhood
acute lymphoblastic leukemia include prophylaxis of the central nervous system. Initially it was thought that the best way of central nervous system prophylaxis is
radiotherapy. But despite its effectiveness this method, may cause late sequelae and complications. In the programme currently used in Poland to treat
acute lymphoblastic leukemia, prophylactic
radiotherapy has been reduced by 50% (12 Gy) and is used only in patients stratified into the high risk group and in patients diagnosed as T-cell ALL (
T-ALL). Complementary to
radiotherapy, intrathecal
methotrexate is given alone or in combination with
cytarabine and
hydrocortisone is given, as well as systemic
chemotherapy with intravenous
methotrexate is administered in high or medium doses (depending on risk groups and
leukemia immunophenotype). Recent studies have shown that high dose irradiation of the central nervous system impairs cognitive development causing
memory loss, visuomotor
coordination impairment, attention disorders and reduction in the intelligence quotient. It has been proved that the degree of
cognitive impairment depends on the radiation dose directed to the medial temporal lobe structures, particularly in the hippocampus and the surrounding cortex. Also,
methotrexate used intravenously in high doses, interferes with the metabolism of
folic acid which is necessary for normal development and the optimal functioning of neurons in the central nervous system. It has been proved that patients who have been treated with high doses of
methotrexate are characterized by reduced memory skills and a lower intelligence quotient. The literature data concerning long term neuroanatomical abnormalities and neuropsychological deficits are ambiguous, and there is still no data concerning current methods of central nervous system prophylaxis with low doses of irradiation in combination with high doses of intravenous
methotrexate.