TriangleHEALTH PROFESSIONAL · SOURCE READING
Central Nervous System (CNS) Prophylaxis for AML
Source: Childhood Acute Myeloid Leukemia Treatment (PDQ®)–Health Professional Version, National Cancer Institute.
Source updated: April 15, 2025 · Captured 2026-09-09.
Selected source text with whitespace normalised. This Triangle page is not an NCI PDQ summary.
Context: Treatment of Childhood AML
Therapy with either radiation or intrathecal chemotherapy has been used to treat CNS leukemia present at diagnosis. However, the use of radiation has essentially been abandoned as a means of prophylaxis because of the lack of documented benefit and long-term sequelae.[55] Intrathecal chemotherapy is used to prevent later development of CNS leukemia. The COG has historically used single-agent cytarabine for both CNS prophylaxis and therapy. Other groups have attempted to prevent CNS relapse by using additional intrathecal agents. Similarly, the ongoing COG AAML1831 (NCT04293562) trial incorporates the use of intrathecal triples (methotrexate, cytarabine, and hydrocortisone).
Source links and citations
CNS involvement in patients with AML and its impact on prognosis has been discussed in the Prognosis and Prognostic Factors section.
Source links and citations
Evidence (CNS prophylaxis):
The COG AAML03P1 (NCT00070174) and AAML0531 (NCT00372593) trials used single-agent cytarabine for prophylaxis.[56] The results of these trials are similar to the findings from the AAML1031 trial.[57]
Source links and citations
The COG AAML03P1 (NCT00070174) and AAML0531 (NCT00372593) trials used single-agent cytarabine for prophylaxis.[56] The results of these trials are similar to the findings from the AAML1031 trial.[57]
CNS1 disease: A low relapse rate was associated with CNS1 disease (3.9%) seen in 71% of enrolled patients.
The COG AAML03P1 (NCT00070174) and AAML0531 (NCT00372593) trials used single-agent cytarabine for prophylaxis.[56] The results of these trials are similar to the findings from the AAML1031 trial.[57]
CNS2 disease: Sixteen percent of patients had CNS2 disease with minimal evidence of CNS leukemia at diagnosis (CNS2 or blasts present when cerebrospinal fluid [CSF] white blood cell count was <5 cells/HPF). These patients were given twice-weekly intrathecal cytarabine until the CSF cleared. Of the 16% of patients who had CNS2 disease, 95.8% had CSF cleared of leukemic blasts. Of those, 11.7% later experienced CNS relapse.
The COG AAML03P1 (NCT00070174) and AAML0531 (NCT00372593) trials used single-agent cytarabine for prophylaxis.[56] The results of these trials are similar to the findings from the AAML1031 trial.[57]
CNS3 disease: CNS3 involvement at diagnosis (13% of patients) conferred even worse outcomes. Despite clearing of leukemic blasts in 90.7% of children, 17.7% later experienced a CNS relapse. In a multivariate analysis, the presence of CNS3 involvement significantly worsened isolated CNS relapse risk (HR, 7.82; P = .003).
Another methodology uses additional intrathecal agents, including triples, a combination of intrathecal cytarabine, hydrocortisone, and methotrexate.[58]
Source links and citations
Another methodology uses additional intrathecal agents, including triples, a combination of intrathecal cytarabine, hydrocortisone, and methotrexate.[58]
The SJCRH reported that after switching from triples (their previous standard treatment) to single-agent cytarabine, the incidence of isolated CNS relapse increased from 0% (0 of 131 patients) to 9% (3 of 33 patients), prompting them to return to triples, which then reproduced a 0% (0 of 79 patients) CNS relapse rate.
Studies cited in this source section
Source citation is not a determination that a study applies to you.
Publication references
Read the original reference and check its publication notices.
Preserved source evidence · Not medical advice