CNS Therapy for Standard-Risk Patients

The CCG-1952 study for National Cancer Institute (NCI) standard-risk patients compared the relative efficacy and toxicity of triple intrathecal chemotherapy (methotrexate, cytarabine, and hydrocortisone) with methotrexate as the sole intrathecal agent in nonirradiated patients.[21]

The CCG-1952 study for National Cancer Institute (NCI) standard-risk patients compared the relative efficacy and toxicity of triple intrathecal chemotherapy (methotrexate, cytarabine, and hydrocortisone) with methotrexate as the sole intrathecal agent in nonirradiated patients.[21]

There was no significant difference in either CNS or non-CNS toxicities.

The CCG-1952 study for National Cancer Institute (NCI) standard-risk patients compared the relative efficacy and toxicity of triple intrathecal chemotherapy (methotrexate, cytarabine, and hydrocortisone) with methotrexate as the sole intrathecal agent in nonirradiated patients.[21]

Although 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), there was no difference in event-free survival (EFS) rates.

The CCG-1952 study for National Cancer Institute (NCI) standard-risk patients compared the relative efficacy and toxicity of triple intrathecal chemotherapy (methotrexate, cytarabine, and hydrocortisone) with methotrexate as the sole intrathecal agent in nonirradiated patients.[21] › Although 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), there was no difference in event-free survival (EFS) rates.

The reduction in CNS relapse rate was especially notable in patients with CNS2 status at diagnosis (lymphoblasts seen in CSF cytospin, but with <5 WBC/high-power field 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).

The CCG-1952 study for National Cancer Institute (NCI) standard-risk patients compared the relative efficacy and toxicity of triple intrathecal chemotherapy (methotrexate, cytarabine, and hydrocortisone) with methotrexate as the sole intrathecal agent in nonirradiated patients.[21] › Although 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), there was no difference in event-free survival (EFS) rates.

There were more bone marrow relapses in the group that received the triple intrathecal chemotherapy, leading to a worse overall survival (OS) rate (90.3% ± 1.5%) compared with the intrathecal methotrexate group (94.4% ± 1.1%; P = .01).

The CCG-1952 study for National Cancer Institute (NCI) standard-risk patients compared the relative efficacy and toxicity of triple intrathecal chemotherapy (methotrexate, cytarabine, and hydrocortisone) with methotrexate as the sole intrathecal agent in nonirradiated patients.[21] › Although 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), there was no difference in event-free survival (EFS) rates.

When the analysis was restricted to patients with B-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, OS, or EFS rates.

The CCG-1952 study for National Cancer Institute (NCI) standard-risk patients compared the relative efficacy and toxicity of triple intrathecal chemotherapy (methotrexate, cytarabine, and hydrocortisone) with methotrexate as the sole intrathecal agent in nonirradiated patients.[21] › Although 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), there was no difference in event-free survival (EFS) rates.

The findings of this trial need to be interpreted within the context of other therapy administered to patients. Dexamethasone, which has been associated with lower CNS relapse rates and improved EFS rates in standard-risk patients in other trials,[8,22] was not used in CCG-1952 (prednisone was the only steroid administered to patients).[23] It is not clear whether the results of the CCG-1952 trial are generalizable to protocols that include the use of dexamethasone and/or other CNS-directed systemic therapies.

The CCG-1952 study for National Cancer Institute (NCI) standard-risk patients compared the relative efficacy and toxicity of triple intrathecal chemotherapy (methotrexate, cytarabine, and hydrocortisone) with methotrexate as the sole intrathecal agent in nonirradiated patients.[21]

In a follow-up study of neurocognitive functioning in the two groups, there were no clinically significant differences.[24][Level of evidence A3]