The Effect of Intensive Intrathecal Chemotherapy on Prognosis of Childhood Lymphoblastic Leukemia with Central Nervous System Involvement: A ۲۰-Year Experience

Publish Year: 1395
نوع سند: مقاله ژورنالی
زبان: English
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تاریخ نمایه سازی: 25 آبان 1402


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 ۱۵% 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 ۱۹۹۵ to May ۲۰۱۴. A total of ۹۰ children diagnosed with acute lymphoblastic leukemia enrolled in this study following parental informed consent. There were ۳۰ children with primary central nervous system involvement and ۶۰ that had central nervous system relapse due to acute lymphoblastic leukemia. Patients were randomly divided into two groups: ۳۰ patients in group A (control group) received triple intrathecal injections every ۲ months according to high risk acute lymphoblastic leukemia protocols for a total of three years. Group A was divided into the following subgroups: A۱ (primary central nervous system involvement; n=۱۵) and A۲ (central nervous system relapse; n=۱۵). Group B (case group) comprised ۶۰ patients that received additional triple intrathecal injections during the fourth and fifth years (۲ years after discontinuation of maintenance chemotherapy). Group B was subdivided as follows: B۱ (primary central nervous system involvement; n=۲۰) and B۲ (central nervous system relapse; n=۴۰). For each patient in group A, two age and sex matched patients in group B were enrolled. Patients were followed for ۲-۱۵ years. Results: From ۱۵ patients  in group A۱  (control with primary  central nervous  system involvement), there were ۵ central nervous system relapses, ۳ bone marrow relapses, and ۲ deaths. Boys had more relapses and deaths than girls (chi square: ۱۵.۶۳; P<۰.۰۰۱). The majority of relapses occurred during the third to fifth years.  In group A۲  (control group with  central nervous system relapse), from ۱۵ patients, there were ۷ with second central nervous system relapses, ۶ with bone marrow relapses, and ۲ deaths. The majority of relapses occurred during the third to fifth years. Boys had more relapses and deaths (P<۰.۰۰۵). From ۲۰ patients in group B۱ (cases with primary central nervous system involvement) only ۲ 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<۰.۰۰۱). In group B۲ (cases with CNS relapse): ۸/۴۰ patients had second central nervous system relapses; ۳ had bone marrow relapse; and ۲ died (P<۰.۰۰۳). Most relapses occurred during the third to fifth years of maintenance therapy. Overall, boys in groups B۱ and B۲ had less mortality and morbidity (chi square: ۲۷.۶; P<۰.۰۰۱) 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.


Mahdi Shahriari

Department of Pediatrics, Hematology Oncology Branch, Shiraz University of Medical Sciences, Shiraz, Iran