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May 26, 2026Open Access

Clinical efficacy of chemotherapy followed by allogeneic hematopoietic stem cell transplantation with continuous tyrosine kinase inhibitor administration in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: a retrospective analysis

Puntos clave

This analysis aims to evaluate the clinical outcomes of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with chemotherapy, allogeneic transplantation, and continuous TKI.
Retrospective analysis of 46 patients with Philadelphia chromosome-positive ALL.
Categorized into transplant cohort (n=27) and non-transplant cohort (n=19).
Primary endpoints included complete molecular remission at 3 months, adverse effects, overall survival, and disease-free survival.
Complete molecular remission rate at 3 months was 54.3%.
5-year overall survival was 65.9% in transplant group vs. 33.7% in non-transplant group (P < 0.05).
2-year overall survival rate for patients receiving allo-HSCT in first complete remission was 75.0% vs. 9.4% for non-transplant individuals (P = 0.0144).

Resumen

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) is associated with a poor prognosis. The advent of tyrosine kinase inhibitors (TKIs) has resulted in improved outcomes. However, the current role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is controversial. This retrospective study aimed to evaluate the clinical outcomes of Ph + ALL patients treated with chemotherapy followed by allo-HSCT, with continuous TKI administration throughout the entire treatment paradigm, providing a theoretical basis for optimizing current therapeutic strategies. A total of 46 patients with Ph + ALL were enrolled and categorized into transplant cohort (n = 27) or non-transplant cohort (n = 19). The primary endpoints were the complete molecular remission (CMR) rate at 3 months post-treatment and adverse effects (AEs); secondary endpoints included disease-free survival (DFS) and overall survival (OS). Overall, the CMR rate at 3 months was 24/46 (54.3%). AEs were well tolerated. The estimated 5-year OS and 5-year DFS rates were 65.9% vs. 33.7% (P < 0.05) and 56.8% vs. 0% (P < 0.0001) in the transplant and non-transplant groups, respectively. Patients who achieved CMR within 3 months demonstrated significantly OS and DFS compared to those who did not (P < 0.05). Further analysis revealed that among patients who failed to attain CMR within 3 months, those receiving allo-HSCT during first complete remission (CR1) exhibited markedly improved 2-year OS rates (75.0% vs. 9.4%, P = 0.0144) and 2-year DFS rates (75.0% vs. 0%, P = 0.0015), in comparison to non-transplant individuals. In multivariate analysis, the absence of TKI maintenance therapy, presence of BCR-ABL p210 transcript, failure to achieve CMR within 3 months, and lack of allo-HSCT were identified as adverse prognostic factors for both OS and DFS. The integration of TKI into the comprehensive treatment strategy for Ph + ALL is associated with favorable survival outcomes. Furthermore, allo-HSCT during CR1 may enhance survival in high-risk patients who failed to achieve CMR at 3 months post-treatment. Therefore, the indication for allo-HSCT should consider early molecular response, disease biology, donor availability, and patient fitness.

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