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 relapse are poor prognostic events in acute lymphoblastic leukemia. Due to severe skeletal and endocrine 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 nervous system relapse is an extremely important way to decrease both mortality and morbidity in childhood leukemia. Methods: This prospective study was conducted from June 1995 to May 2014. A total of 90 children diagnosed with acute lymphoblastic leukemia enrolled in this study following parental informed consent. There were 30 children with primary central nervous system involvement and 60 that had central nervous system relapse due to acute lymphoblastic leukemia. Patients were randomly divided into two groups: 30 patients in group A (control group) received triple intrathecal injections every 2 months according to high risk acute lymphoblastic leukemia protocols for a total of three years. Group A was divided into the following subgroups: A1 (primary central nervous system involvement; n=15) and A2 (central nervous system relapse; n=15). Group B (case group) comprised 60 patients that received additional triple intrathecal injections during 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 sex matched 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 system involvement), 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 of relapses occurred during the third to fifth years. In group A2 (control group with central nervous system relapse), from 15 patients, there were 7 with second central nervous system relapses, 6 with bone marrow relapses, and 2 deaths. The majority of relapses occurred during the third to fifth years. Boys had more relapses and deaths (P < 0.005). From 20 patients in group B1 (cases with primary central nervous system involvement) only 2 boys had central nervous system relapses. There were no bone marrow relapses and no male patients died. No relapse or deaths occurred in female patients (Fisher’s exact test: P < 0.001). In group B2 (cases with CNS relapse): 8/40 patients had second central nervous system relapses; 3 had bone marrow relapse; and 2 died (P < 0.003). Most relapses occurred during the third to fifth years of maintenance therapy. Overall, boys in groups B1 and B2 had less mortality and morbidity (chi square: 27.6; P < 0.001) and better prognosis. Conclusion: Extended intrathecal injections after discontinuation of maintenance chemotherapy is advisable for cases with primary central nervous system involvement and central nervous system relapses. However, we propose that national and international studies with greater number of patients should be conducted.