A new treatment paradigm that reduces the use of both cranial radiotherapy and hematopoietic stem-cell transplantation (HSCT) appears to yield promising outcomes among pediatric and young adult patients with T-cell acute lymphoblastic leukemia (ALL-T11), according to research published in The Lancet Haematology.

Among pediatric and adolescent patients, it is critical to reduce long-term adverse events, which may arise from cranial radiation therapy and HSCT. For this multicenter study based in Japan, researchers evaluated the safety and efficacy of a combination nelarabine, intensified L-asparaginase, and protracted intrathecal therapy among patients with ALL-T11.

Overall, 310 patients were enrolled and underwent risk assessment; 168, 103, and 39 patients were stratified into standard-, high-, and very high-risk categories, respectively. A total of 39 patients received off-protocol treatment prior to risk assessment. In the standard-, high-, and very high-risk groups, the median ages were 9, 9, and 8, respectively, 71%, 65%, and 62% of patients were male sex, and 57%, 53%, and 49% of patients had a mediastinal mass present.

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Patients with very high-risk disease were randomly assigned to 1 of 2 groups: group A (14 patients), which received Berlin-Frankfurt-Münster-based block therapy, and group B (12 patients), which received another block therapy that included high-dose dexamethasone.

After remission induction therapy, the composite complete remission rate — which comprised both complete remissions plus complete remissions in suppression — was 89%. A tot al of 35 patients (10%) proceeded to HSCT.

Analysis showed, after a median follow-up of 5.2 years, that the 3-year event-free survival rate was 86.4% (95% CI, 82.3-89.7), whereas the 3-year overall survival rate was 91.3% (95% CI, 87.7-93.8).

In groups A and B, 12 and 6 patients, respectively, had minimal residual disease disappearance (proportions, 0.86 and 0.5). The most frequently noted grade 3 or worse adverse event was febrile neutropenia (84%), and 3 treatment-related deaths were recorded. Grade 3 peripheral neuropathy was also noted in 3% of patients.

“Better use of L-asparaginase, using different formulations such as PEG-asparaginase, and solving the problem of silent inactivation might further improve outcomes for patients with T-cell acute lymphoblastic leukaemia,” the authors wrote in their report.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.


Sato A, Hatta Y, Imai C, et al. Nelarabine, intensive L-asparaginase, and protracted intrathecal therapy for newly diagnosed T-cell acute lymphoblastic leukaemia in children and young adults (ALL-T11): a nationwide, multicenter, phase 2 trial including randomisation in the very high-risk group. Lancet Haematol. Published online May 8, 2023. doi:10.1016/S2352-3026(23)00072-8