Clinical features and initial treatment outcomes of pediatric B-cell acute lymphoblastic leukemia with P2RY8::CRLF2 fusion positivity: a case series

Background: P2RY8::CRLF2 fusion is a recurrent CRLF2 (cytokine receptor-like factor 2) rearrangement in pediatric B-cell acute lymphoblastic leukemia (B-ALL) and is frequently associated with Philadelphia chromosome-like features and kinase pathway activation. However, clinical data on Chinese children with this lesion remain limited, and its early response under contemporary risk-adapted chemotherapy is not fully defined. We report a single-center case series to describe the clinical, molecular, and early treatment characteristics of this rare subgroup.

Case Description: Seven consecutive children with newly diagnosed P2RY8::CRLF2 fusion-positive B-ALL treated between September 2017 and July 2024 were retrospectively reviewed. The median age at diagnosis was 3 years and 11 months, and the median initial white blood cell (WBC) count was 25.65×10⁹/L. 
All patients had precursor B-cell immunophenotype. Concurrent genetic abnormalities included RAS pathway mutations in three patients, PAX5 fusions in two, and a JAK mutation in one. Two patients were treated according to the CCCG-ALL-2015 protocol and five according to the CCCG-ALL-2020 protocol. One patient received ruxolitinib during induction, and another patient with poor early response received ruxolitinib plus blinatumomab. Five patients achieved minimal residual disease (MRD) negativity on day 19, and six achieved MRD <0.01% with disappearance of the fusion transcript by day 46; the remaining patient became MRD-negative after salvage immunotherapy. After a median follow-up of 32 months, all patients remained in continuous complete remission (CR), although three were still receiving therapy.

Conclusions: Pediatric P2RY8::CRLF2 fusion-positive B-ALL may show molecular heterogeneity, including recurrent RAS pathway lesions. Favorable early responses were observed under contemporary intensified chemotherapy with individualized targeted or immunotherapeutic interventions. Because of the small sample size, single-center design, and limited follow-up, these findings should be interpreted cautiously and require validation in multicenter cohorts.