Andreea ANDRUNACHE, Bogdan IONESCU, Alexandra GHIAUR, Camelia STĂNCIOAICA, Roxana HÎRJAN, Aurelia TATIC, Ana Manuela CRIȘAN, Alexandru BARDAȘ, Razvan STOIA, Mihaela CÂRSTEA, Daniel CORIU
Abstract
Acute lymphoblastic leukemia (ALL) is a subtype of hematological malignancy characterized by uncontrolled proliferation of immature lymphoid precursor cells. This study presents a retrospective analysis of a cohort of patients diagnosed with Philadelphia-positive acute lymphoblastic leukemia between 2020 and 2024 at the Fundeni Clinical Institute. This study was conducted retrospectively at a single center, utilizing data extracted from the electronic medical records maintained by the hospital. Among the 203 individuals diagnosed with ALL at our institution, 47 patients were identified as harboring the BCR::ABL fusion gene and were subsequently included in the analysis.
The median age of the study cohort was 49 years (range: 18–78 years), with a female predominance (female-to-male ratio: 1.28:1). Regarding therapeutic strategies, 57.4% of patients received induction therapy based on the GRAAPH 2005 (Group for Research on Adult Acute Lymphoblastic Leukemia Philadelphia-positive) protocol, which combines low-intensity chemotherapy with tyrosine kinase inhibitors. Post-induction, 76.6% of patients achieved complete morphological remission. Over a follow-up period of 54 months, 51% of patients experienced at least one relapse. Notably, mutations in the ABL1 kinase domain were detected in seven of the relapsed cases.
In accordance with current national protocols, the therapeutic approach for patients with relapsed or refractory (R/R) disease includes chemotherapy in combination with second- or third-generation tyrosine kinase inhibitors (TKIs), such as Dasatinib or Ponatinib. In recent years, Blinatumomab and Inotuzumab-Ozogamicin have been approved in our country as monotherapy options for the treatment of Philadelphia-positive ALL in patients who have progressed beyond second-line therapy.
The results of this real-world study align with existing literature regarding the efficacy of TKI-based therapies in combination with low-dose chemotherapy. Ph + R/R ALL remains a therapeutic challenge, since it is associated with resistant mutations in the BCR-ABL tyrosine kinase domain and a reduced survival rate.
Keywords: Philadelphia Positive Acute Lymphoblastic Leukemia, Tyrosine Kinase Inhibitors, Real-World Experience
https://doi.org/10.59854/dhrrh.2024.2.4.189
