KEY TAKEAWAYS
- The study aimed to investigate the clinical significance of low-level BCR::ABL1 transcripts in children with Ph-negative ALL.
- Low-level BCR::ABL1 positivity at diagnosis in children with Ph- ALL did not adversely impact event-free or OS.
Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) is a high-risk leukemia with poor outcomes in the absence of tyrosine kinase inhibitor (TKI) therapy. Incorporation of TKI therapy has improved outcomes in this subset of patients. Testing for the presence of the Philadelphia chromosome at diagnosis by at least 2 methods, such as karyotype, fluorescent in situ hybridization (FISH), and reverse transcription polymerase chain reaction (RT-PCR) for the BCR::ABL1 transcript, is essential.
While these methods are effective for diagnosis, the significance of a low-level BCR::ABL1 transcript by RT-PCR in the absence of the Philadelphia chromosome on karyotype or by FISH remains unclear.
Lucy E Cain and the team aimed to characterize the clinical significance of low-level BCR::ABL1 transcripts in children with Ph-negative ALL.
This retrospective study included children diagnosed with acute leukemia from 2010 to 2020 at a single institution. Patients positive for the BCR::ABL1 transcript by qualitative RT-PCR and negative for t(9;22) by karyotype or FISH were included.
Patient demographics, cytogenetic and molecular features at diagnosis and relapse, treatment, and outcomes were analyzed. Event-free survival and overall survival were estimated using the Kaplan-Meier method.
Approximately 47 of 306 (15%) patients with Ph- ALL had low-level BCR::ABL1 detected by RT-PCR. The majority of patients (77%) had B-cell ALL. The e1a2 transcript was most frequently detected, identified in 43 (91%) patients. BCR::ABL1 transcripts were quantifiable in 12/43 (28%) patients, with a median of 0.0008% (range 0.0003-0.095%). Seven patients (15%) experienced a relapse. No patients with low-level BCR::ABL1 at diagnosis developed Ph + ALL at relapse.
There was no significant difference in 5-year event-free (77% versus 81%, P= 0.407) or overall survival (86% versus 91%, P= 0.3) between children with low-level BCR::ABL1 (n = 47) and those without (n = 259).
The study concluded that the Low-level BCR::ABL1 positivity is a relatively common finding in children with newly diagnosed Ph- ALL. This finding does not appear to adversely affect outcomes for patients treated using a contemporary risk-adapted approach.
No specific funding for this work was received.
Source: https://pubmed.ncbi.nlm.nih.gov/39291932/
Cain LE, Mirochnik O, Stevens MM, et al. (2024). “Low-Level BCR::ABL1 Transcript at Diagnosis in Childhood Leukemia: A 10-Year Single Institution Study.” Genes Chromosomes Cancer. 2024;63(9):e23269. doi:10.1002/gcc.23269
