B-ALL Relapses After Autologous Stem Cell Transplantation Associated With a Shift from e1a2 to e14a2 Transcripts: A Case Report.

Background/aim: The Philadelphia chromosome is found in 30% of acute lymphoblastic leukemia (ALL) patients, a distinct ALL subgroup where the BCR-ABL fusion gene is associated with poor prognosis. Treatment with tyrosine kinase inhibitors (TKIs) often induces complete remission and these patients subsequently undergo an autologous stem cell transplantation (ASCT). However, 20% of subjects experience a relapse associated with the selection of point-mutations in the BCR-ABL kinase domain. We report the clinical evolution of a Philadelphia-positive ALL patient co-expressing the e1a2 and e14a2 BCR-ABL transcript at diagnosis.

Materials And Methods: Multiplex reverse transcriptase (RT)-PCR was used to detect BCR-ABL transcripts and their levels were measured by quantitative Real Time PCR. Clonal sequencing and next-generation sequencing (NGS) were used to identify mutations.

Results: Although the patient underwent ASCT following treatment with multiple TKIs, he relapsed twice. The first time he exhibited the e1a2 transcript and the second time he presented only the e14a2 variant. Mutation analysis, performed by clonal sequencing and NGS, detected two alterations after the first relapse and a single mutation at the time of the second relapse.

Conclusion: The observed shift from the e1a2 to the e14a2 variant and the selection of TKI-resistant clones heavily contributed to the fatal evolution of the disease.