Efficacy Outcomes With C-MTX in Newly Diagnosed Patients With Pediatric T-Cell Lymphoblastic Lymphoma

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As reported in the Journal of Clinical Oncology by Hayashi et al, the Children’s Oncology Group AALL0434 study has shown “excellent” outcomes with Capizzi-based methotrexate/pegaspargase (C-MTX) treatment in patients with newly diagnosed pediatric T-cell lymphoblastic lymphoma (T-LL). The addition of nelarabine to treatment in high-risk patients did not improve outcomes.

Study Details

In the trial, 299 patients aged 1 to 31 years received the augmented Berlin-Frankfurt-Muenster (ABFM) C-MTX regimen. A total of 121 patients had high-risk disease, defined as ≥ 1% minimal detectable disease in the bone marrow at diagnosis or receipt of prior steroid treatment. High-risk patients were randomly assigned to receive (n = 60) vs not receive (n = 61) six 5-day courses of nelarabine incorporated into ABFM C-MTX treatment.

Induction failure was defined as failure to achieve at least partial response by the end of 4-week induction treatment. Patients with induction failure had nelarabine added to treatment (n = 2). No patients received prophylactic cranial radiation. Patients with central nervous system (CNS) 3 disease (cerebrospinal fluid white blood cell count > 5/μL with blasts or cranial nerve palsies, brain/eye involvement, or hypothalamic syndrome) were not eligible for the trial.

Treatment Outcomes

Median follow-up was 4.9 years. At the end of induction, 98.8% of 282 evaluable patients had at least a partial response. Among all patients, 4-year event-free survival and overall survival were 84.7% and 89.0%. From end of induction, 4-year disease-free survival was 85.9%.

Disease-free survival at 4 years was 85.0% among standard-risk patients vs 87.4% among all high-risk patients (P = .2866). Event-free survival at 4 years was 82.4% among 176 patients with minimal detectable disease < 1% vs 89.5% among 97 patients with minimal detectable disease ≥ 1% (P = .3084).

Among high-risk patients, 4-year disease-free survival was 85.1% among those not receiving nelarabine vs 85.0% among those receiving nelarabine (P = .8338). The two patients who received nelarabine on the basis of induction failure were event-free during follow-up.


  • Among all patients, 4-year event-free survival and overall survival were 84.7% and 89.0%.
  • No difference in disease-free survival was observed between standard-risk and high-risk patients, with no benefit of adding nelarabine being observed among high-risk patients.

Additional analysis according to disease stage and tumor response did not indicate thresholds associated with differences in event-free survival. CNS relapse occurred in four patients (2%).

Nonrelapse deaths were observed in five patients, including three patients in the standard-risk group (due to fungal infection, unknown cause, and hemophagocytic lymphohistiocytosis, respectively) and two in the high-risk group (due to pancreatitis and cerebral edema, respectively). One patient developed a benign tumor, with no secondary malignancies being observed.

The investigators concluded, “COG AALL0434 produced excellent outcomes in one of the largest trials ever conducted for patients with newly diagnosed T-LL. The COG ABFM regimen with C-MTX provided excellent event-free survival and overall survival without cranial radiation.”

Robert J. Hayashi, MD, of the Division of Pediatric Hematology/Oncology, Washington University School of Medicine, St. Louis, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the National Institutes of Health and St. Baldrick’s Foundation. For full disclosures of the study authors, visit

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