Clinical Characteristics and Prognostic Analysis of Non-NPM1-ALK Fusions in Pediatric Patients With ALK-Positive Anaplastic Large-Cell Lymphoma: A Single-Center Retrospective Study in China.

PURPOSE: Non-NPM1-ALK fusions in pediatric anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALK+ ALCL) are rare and insufficiently characterized in Chinese populations. This study analyzed the clinical features, treatment responses, and potential prognostic implications of these variants.

METHODS

In this retrospective study, eight pediatric patients with ALK+ ALCL and non-NPM1-ALK fusions were diagnosed between April 2017 and April 2025. For prognostic comparison, a cohort of 107 newly diagnosed patients with NPM1-ALK fusions was used. Clinical data, treatment courses, and outcomes were reviewed. Event-free survival (EFS) was estimated using the Kaplan-Meier method.

RESULTS

Among 128 ALK+ ALCL patients, 8 (6.3%) had non-NPM1-ALK fusions (TPM3, n = 3; ATIC, n = 2; CLTC, MYH9, TRAF1, n = 1 each). At a median follow-up of 17.5 months (range, 1.2-97.9), all patients were alive. Analysis of patients with non-NPM1-ALK fusions (n = 7, newly diagnosed) indicated a trend toward inferior 5-year EFS compared with the NPM1-ALK group. Within the non-NPM1-ALK cohort, no events were observed in the three patients TPM3-ALK fusions, while four patients with other fusion types experienced relapse or disease progression. ALK inhibitors (crizotinib/alectinib) were associated with sustained remission in three patients with relapsed/refractory disease.

CONCLUSION

Pediatric ALK+ ALCL with non-NPM1-ALK fusions exhibits diverse clinical features and outcomes. TPM3-ALK fusions might correlate with a more favorable course, while other variants may face a potentially higher relapse risk. ALK inhibitors showed promising efficacy in the salvage setting. These preliminary findings highlight the need for larger prospective studies to validate mutation-specific risk stratification and therapeutic strategies.