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Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI] - CNS-Directed Therapy for Childhood ALL

Table 2. CNS-Directed Treatment Regimens for Newly Diagnosed Childhood ALL continued...

Unlike intrathecal cytarabine, intrathecal methotrexate has a significant systemic effect, which may contribute to prevention of marrow relapse.[5]

CNS-Penetrant Systemic Chemotherapy

In addition to therapy delivered directly to the brain and spinal fluid, systemically administered agents are also an important component of effective CNS prophylaxis. The following systemically administered drugs provide some degree of CNS prophylaxis:

  • Dexamethasone.
  • L-asparaginase.
  • High-dose methotrexate with leucovorin rescue.

Evidence (CNS-penetrant systemic chemotherapy):

  1. In a randomized Children's Cancer Group (CCG) study of standard-risk patients who all received the same dose and schedule of intrathecal methotrexate without cranial irradiation, oral dexamethasone was associated with a 50% decrease in the rate of CNS relapse compared with oral prednisone.[6]
  2. In a standard-risk ALL trial (COG-1991), lower-dose intravenous methotrexate without rescue significantly reduced the CNS relapse rate compared with oral methotrexate given during each of two interim maintenance phases.[7]
  3. In a randomized clinical trial conducted by the Pediatric Oncology Group, T-cell ALL patients who received high-dose methotrexate experienced a significantly lower CNS relapse rate than patients who did not receive high-dose methotrexate.[8]

Cranial Radiation

The proportion of patients receiving cranial radiation has decreased significantly over time. At present, most newly diagnosed children with ALL are treated without cranial radiation. Many groups administer cranial radiation only to those patients considered to be at highest risk for subsequent CNS relapse, such as those with documented CNS leukemia at diagnosis (as defined above) (>5 WBC/μL with blasts; CNS3) and/or T-cell phenotype with high presenting WBC count.[9] In patients still receiving cranial radiation, the dose has been significantly reduced.

Ongoing trials seek to determine whether radiation can be eliminated from the treatment of all children with ALL without compromising survival or leading to increased rate of toxicities from upfront and salvage therapies.[10,11]

CNS Therapy for Standard-Risk Patients

Intrathecal chemotherapy without cranial radiation, given in the context of appropriate systemic chemotherapy, results in CNS relapse rates of less than 5% for children with standard-risk ALL.[10,11,12,13,14,15]

The use of cranial radiation does not appear to be a necessary component of CNS-directed therapy for these patients.[16,17]

Evidence (triple intrathecal chemotherapy vs. intrathecal methotrexate):

  1. The CCG-1952 study for National Cancer Institute (NCI) standard-risk patients compared the relative efficacy and toxicity of triple intrathecal chemotherapy (methotrexate, prednisone, and cytarabine) with methotrexate as the sole intrathecal agent in nonirradiated patients.[18]
    1. There was no significant difference in either CNS or non-CNS toxicities.
    2. Triple intrathecal chemotherapy was associated with a lower rate of isolated CNS relapse (3.4% ± 1.0% compared with 5.9% ± 1.2% for intrathecal methotrexate; P = .004).
      • This effect was especially notable in patients with CNS2 status at diagnosis (lymphoblasts seen in CSF cytospin, but with <5 WBC/high-power field [hpf] on CSF cell count); the isolated CNS relapse rate was 7.7% ± 5.3% for CNS2 patients who received triple intrathecal chemotherapy compared with 23.0% ± 9.5% for those who received intrathecal methotrexate alone (P = .04).
      • There were more bone marrow relapses in the group that received the triple intrathecal chemotherapy, leading to a worse overall survival (OS) (90.3% ± 1.5%) compared with the intrathecal methotrexate group (94.4% ± 1.1%; P = .01).
      • When the analysis was restricted to patients with precursor B-cell ALL and rapid early response (M1 marrow on day 14), there was no difference between triple and single intrathecal chemotherapy in terms of rates of CNS relapse rate, OS, or event-free survival (EFS).
    3. In a follow-up study of neurocognitive functioning in the two groups, there were no clinically significant differences.[19][Level of evidence: 1iiC]
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WebMD Public Information from the National Cancer Institute

Last Updated: February 25, 2014
This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.
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