LEUKOENCEPHALOPATHY IN CHILDHOOD HEMATOPOIETIC NEOPLASM CAUSED BY MODERATE-DOSE METHOTREXATE AND PROPHYLACTIC CRANIAL RADIOTHERAPY - AN MR ANALYSIS

Purpose: The main purpose of this study was to determine influential f actors related to minor leukoencephalopathy (LEP) caused by moderate-d ose methotrexate (MTX) and prophylactic cranial radiotherapy (CRT) in childhood hematopoietic malignancies, We also compared the incidence o f LEP following this treatment to that reported in the literature foll owing treatment with high-dose MTX alone. Methods and Materials: Thirt y-eight pediatric patients of hematopoietic malignancies (37 acute lym phoblastic leukemias, 1 non-Hodgkin lymphoma) who were given CRT (18-2 4 Gy) as well as prophylactic intrathecal and per os MTX were studied for leukoencephalopathy by magnetic resonance (MR) imaging, All the pa tients were free from grave neuropsychiatric disturbances, The data we re examined to elucidate the influential ones of five factors (patient s' age, doses of intrathecal and per os MTX, dose of CRT, interval bet ween treatment, and MR study) to develop LFP using multiple regression analysis, To compare the effect of moderate-dose MTX and prophylactic CRT on LEP to that of high-dose MTX alone, we conducted literature re view. Results: Seven out of 38 patients (18%) developed LEP, From mult iple regression analysis and partial correlation coefficients, the age and CRT dose seemed influential in the subsequent development of LEP, The incidence of LEP following treatment with moderate-dose MTX and p rophylactic CRT appears to be less than that reported in the literatur e following treatment with intravenous high-dose MTX, However, even mo derate-dose MTX in combination with CRT can result in a significant in cidence of MR-detectable LEP, particularly in children 6 years of age or younger receiving 24 Gy. Conclusion: Leukoencephalopathy was caused by moderate-dose MTX and prophylactic CRT in pediatric patients, prob ably less frequently than by high-dose MTX treatment alone, The influe ntial factors were patient's age and CRT dose.