Ph+ ALL in Chinese Children: Diagnosis, Treatment, and Survival

This is a national multicenter retrospective real-world study, aiming to investigate the diagnosis, treatment, and survival status of pediatric Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in China. Ph+ ALL accounts for 3%-5% of all childhood ALL cases and was historically associated with poor prognosis. The widespread clinical application of tyrosine kinase inhibitors (TKIs) has significantly improved the overall survival (OS) of pediatric Ph+ ALL, with current OS rates reaching 70%-80%, and most patients no longer require hematopoietic stem cell transplantation (HSCT).

Minimal residual disease (MRD) monitoring is the core indicator for evaluating treatment efficacy and prognosis of Ph+ ALL. Common clinical MRD detection methods include multiparameter flow cytometry (MFC), quantitative polymerase chain reaction (qPCR) targeting BCR-ABL1 fusion gene and immunoglobulin/T-cell receptor (Ig/TR) gene rearrangement, and next-generation sequencing (NGS). However, prominent inconsistent MRD results across different detection methods are frequently observed during clinical follow-up. A specific subtype termed CML-like ALL has been defined, in which BCR::ABL fusion genes are detected not only in leukemic lymphoblasts but also in non-leukemic myeloid and lymphoid cells. Distinct from typical Ph+ ALL, the MRD level of CML-like ALL lacks prognostic predictive value, and such patients are prone to treatment-related mortality rather than disease relapse, leading to potential overtreatment.

Existing overseas and domestic studies have confirmed the clinical heterogeneity between CML-like ALL and typical Ph+ ALL, but large-sample real-world data focusing on Chinese pediatric populations remain insufficient. This study retrospectively enrolls pediatric Ph+ ALL patients newly diagnosed between January 1, 2015, and December 31, 2024. from multiple Chinese medical centers. All enrolled children received standardized TKI therapy and simultaneous paired MRD detection via MFC and PCR at consistent time points. Patients are stratified into CML-like ALL and typical Ph+ ALL groups.

The primary study outcomes include national real-world survival data (OS, event-free survival [EFS]) of pediatric Ph+ ALL, the incidence and clinical characteristics of CML-like ALL, and the differences in diagnosis, treatment, MRD dynamic changes, and prognosis between the two subtypes. This study adopts standardized real-world data collection and rigorous statistical analysis, with a target enrollment of over 500 patients to ensure statistical validity. This retrospective study involves no additional clinical intervention or increased medical risks for patients, with all data fully desensitized to protect privacy. The findings will supplement Chinese clinical evidence for individualized risk stratification and precise treatment of pediatric Ph+ ALL, optimize overtreatment status of CML-like ALL, and improve long-term survival outcomes of affected children.

Inclusion criteria

• Age at diagnosis ranging from 1 month to 18 years.
• Positive for the BCR::ABL fusion gene.
• Serial quantitative MRD testing was routinely performed using multiparameter flow cytometry (MFC) and PCR (qRT-PCR or ddPCR) during treatment, with samples collected for both assays at identical time points.
• Standardized TKI therapy (imatinib, dasatinib, or other TKIs) was administered.

Exclusion criteria

• Mixed-phenotype acute leukemia.
• Irregular treatment not administered in accordance with the chemotherapy protocol.
• Previous or concurrent other malignancies.
• Failure to receive standardized TKI therapy due to intolerance to TKIs, contraindications to TKI treatment, or other relevant factors.