the effect of intensive intrathecal chemotherapy on prognosis of childhood lymphoblastic leukemia with central nervous system involvement: a 20-year experience

Background: primary central nervous system involvement and central nervous system relapseare poor prognostic events in acute lymphoblastic leukemia. due to severe skeletal andendocrine complications of craniospinal radiotherapy, only cranial radiotherapy is advisable.however only 15% of the cases with central nervous system relapse may remain in remission;a second central nervous system or bone marrow relapse is common. prevention of central nervoussystem relapse is an extremely important way to decrease both mortality and morbidity inchildhood leukemia.methods: this prospective study was conducted from june 1995 to may 2014. a total of90 children diagnosed with acute lymphoblastic leukemia enrolled in this study following parentalinformed consent. there were 30 children with primary central nervous system involvementand 60 that had central nervous system relapse due to acute lymphoblastic leukemia. patientswere randomly divided into two groups: 30 patients in group a (control group) received tripleintrathecal injections every 2 months according to high risk acute lymphoblastic leukemiaprotocols for a total of three years. group a was divided into the following subgroups: a1 (primarycentral nervous system involvement; n=15) and a2 (central nervous system relapse; n=15). groupb (case group) comprised 60 patients that received additional triple intrathecal injectionsduring the fourth and fifth years (2 years after discontinuation of maintenance chemotherapy).group b was subdivided as follows: b1 (primary central nervous system involvement; n=20)and b2 (central nervous system relapse; n=40). for each patient in group a, two age and sexmatched patients in group b were enrolled. patients were followed for 2-15 years.results: from 15 patients in group a1 (control with primary central nervous systeminvolvement), there were 5 central nervous system relapses, 3 bone marrow relapses, and 2 deaths.boys had more relapses and deaths than girls (chi square: 15.63; p < 0.001). the majority ofrelapses occurred during the third to fifth years. in group a2 (control group with centralnervous system relapse), from 15 patients, there were 7 with second central nervous systemrelapses, 6 with bone marrow relapses, and 2 deaths. the majority of relapses occurred duringthe third to fifth years. boys had more relapses and deaths (p < 0.005). from 20 patients in groupb1 (cases with primary central nervous system involvement) only 2 boys had central nervoussystem relapses. there were no bone marrow relapses and no male patients died. no relapseor deaths occurred in female patients (fisher’s exact test: p < 0.001). in group b2 (cases withcns relapse): 8/40 patients had second central nervous system relapses; 3 had bone marrowrelapse; and 2 died (p < 0.003). most relapses occurred during the third to fifth years ofmaintenance therapy. overall, boys in groups b1 and b2 had less mortality and morbidity (chisquare: 27.6; p < 0.001) and better prognosis.conclusion: extended intrathecal injections after discontinuation of maintenancechemotherapy is advisable for cases with primary central nervous system involvement and centralnervous system relapses. however, we propose that national and international studies with greaternumber of patients should be conducted.