Effect of Methotrexate and Corticosteroid Strategies on Neurocognitive Function in Patients With B-Lineage ALL


Key Points

  • Neither method of methotrexate delivery nor corticosteroid used had an effect on neurocognitive measures in patients with high-risk B-lineage acute lymphoblastic leukemia.
  • Diagnosis at age < 10 years was associated with poorer IQ and processing speed.

In a Children’s Oncology Group (COG) study (AALL06N1) reported in the Journal of Clinical Oncology, Hardy et al found that age < 10 years at diagnosis was associated with poorer neurocognitive function in patients with high-risk B-lineage acute lymphoblastic leukemia regardless of methotrexate and corticosteroid treatment strategies.

Study Details

The study was designed to assess neurocognitive impact on a subgroup of patients initially enrolled in COG study AALL0232; in the latter study, patients were randomized to receive high-dose methotrexate with leucovorin rescue or escalating-dose methotrexate with PEG-asparaginase (Oncaspar) without leucovorin rescue and were also randomized to receive corticosteroid therapy with dexamethasone or prednisone. Patients in the current analysis had to have been diagnosed at between 1 and 18 years; exclusion criteria included preexisting neurodevelopmental disability, significant sensory impairment, central nervous system involvement, treatment with cranial radiation, and recurrent disease.

The current analysis included 192 patients undergoing neurocognitive evaluation of intellectual functioning (IQ), working memory, and processing speed performed 8 to 24 months after treatment completion. Of them, 91 and 101 received high-dose and escalating-dose methotrexate, respectively, and 84 and 108 received dexamethasone and prednisone, respectively.

Neurocognitive Function

In an analysis controlling for ethnicity, race, age, gender, insurance status, and time off treatment, neither methotrexate strategy nor corticosteroid assignment was related to differences in neurocognitive outcomes. Patients aged < 10 years at diagnosis (n = 89) had a significantly lower estimated IQ (P < .001) and processing speed scores (P = .02) vs those aged ≥ 10 years. Estimated IQ was significantly lower among patients with U.S. public health insurance vs those with U.S. private or military insurance (P < .001).

The investigators concluded: “Children with high-risk B-lineage [acute lymphoblastic leukemia] who were age < 10 years at diagnosis are at risk for deficits in IQ and [processing speed] in the absence of cranial radiation, regardless of [methotrexate] delivery or corticosteroid type. These data may serve as a basis for developing screening protocols to identify children who are at high risk for deficits so that early intervention can be initiated to mitigate the impact of therapy on neurocognitive outcomes.”

The study was supported by COG Group Chair and COG Statistics and Data Center grants and by American Lebanese Syrian Association Charities.

Naomi Winick, MD, of The University of Texas Southwestern Medical Center in Dallas, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.