Secondary Brain Tumors In Children Treated For Acute Lymphoblastic Leukemia At St Jude Children's Research Hospital

Reviewers: John Han-Chih Chang, MD
Source: Journal of Clinical Oncology 1998; Volume 16: pages 3761 - 67.

Summary

The St. Jude Children's Research Hospital has published their experience on the incidence of secondary brain tumors in patients treated for childhood acute lymphoblastic leukemia (ALL). All patients treated on various protocols were reviewed. Out of 1612 consecutive children with ALL, 21 patients developed a subsequent brain tumor with a median follow-up of nearly 16 years. A little less than half of those patients had developed high grade gliomas, while the rest were meningiomas and one low grade glioma. The cumulative incidence of secondary brain tumors after ALL treatment is 1.39% at 20 years. The overall median latency period was 12.6 years; with 9 years for high grade gliomas and 19 years for meningiomas. Risk factors for developing a secondary brain tumor were the presence of central nervous system (CNS) leukemia (independent of radiation dose), the use of cranial irradiation and the dose of radiation. A higher incidence of high grade gliomas was associated with presence of CNS leukemia (also irrespective of radiation dose) and age less than 6 years.

Background/Discussion/Conclusion

Leukemia is the most common malignancy in children. The most common type is ALL (over 80%). Fortunately, advances in treatment have increased the long term remission rate on the order of 60 - 75%. In the 1960's, it was discovered that despite high initial complete response (CR) rates, long term remissions were less than 25% due to CNS relapses. Prophylactic craniospinal axis irradiation was initially utilized to improve the control and durable long term remission rates. Later, it was discovered that intrathecal chemotherapy along with cranial only irradiation was equivalent to CSI with less toxicity. Many of the recent studies have shown that high dose intravenous and intrathecal chemotherapy was equivalent in prevention of CNS relapse in low risk ALL ( < 25000 WBC, no CNS involvement and B-cell disease). Select high risk patients are currently the only group receiving CNS prophylaxis with cranial irradiation and intrathecal chemotherapy. As patients get further out from completion of successful treatment for ALL, long term toxicities become more evident.

The St. Jude Total Therapy Program is a series of protocols utilized on childhood ALL patients from 1967 - 1988. The data regarding secondary brain tumors are summarized above and this corroborates other reported series.1-3 There seems to be a definite association of secondary brain tumors with cranial irradiation and RT dose, but no significant correlation with intrathecal chemotherapy. As a result of this and other series, only select high risk ALL patients receive cranial irradiation along with intrathecal chemotherapy.