What is the role of cranial irradiation in the treatment of pediatric acute lymphoblastic leukemia (ALL)?

Updated: Jan 03, 2019
  • Author: Vikramjit S Kanwar, MBBS, MBA, MRCP(UK), FAAP; Chief Editor: Jennifer Reikes Willert, MD  more...
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Answer

Although cranial irradiation (CXRT) effectively prevents overt CNS relapse, concern about subsequent neurotoxicity and brain tumors led to a desire to replace this modality with intensive intrathecal and systemic chemotherapy.

The UKALL XI trial (1990-97) administered high-dose intravenous methotrexate (HDMTX) (6–8 g/m2) with intrathecal methotrexate (ITMTX) compared with ITMTX alone, and demonstrated decreased isolated and combined CNS relapse for patients with standard risk ALL with the former. For patients with high risk ALL, HDMTX with ITMTX were compared with CXRT and ITMTX, and although CNS relapses were significantly fewer with the latter, 10-year EFS was not significantly different (55·2% vs 52·1%). [17]

The DLCSG ALL-7 and ALL-8 trials (1988-1997) omitted CXRT except for 2% of patients who had overt CNS-3 disease and were still able to demonstrate an overall CNS relapse rate of only 5.5%. [18]

Pui et al confirmed these findings in the study Total XV (2000-2007); prophylactic CXRT was omitted from treatment for all groups of patients, including CNS-3, with an overall CNS relapse rate of 3.9%. [15]

Currently, whether prophylactic CXRT is necessary for patients with very-high-risk ALL is unclear. The current COG VHR ALL and Ph+ ALL trials do not routinely administer prophylactic CXRT, although patients with CNS-3 continue to receive CXRT.


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