BCR-ABL halving time indicates CML prognosis during front-line TKI

By Lynda Williams, Senior medwireNews Reporter

Calculating halving time of the BCR-ABL transcript after 3 months may help determine prognosis in chronic myeloid leukaemia (CML) patients undergoing first-line tyrosine kinase inhibitor (TKI) therapy, say researchers.

Of 50 chronic phase CML patients beginning imatinib (n=33), nilotinib (n=10), dasatinib (n=4) or rotational nilotinib and imatinib (n=3) treatment, 68% achieved a BCR-ABL transcript ratio of 10% or less at the 3-month checkpoint.

Major molecular remission at 12 months, defined as a BCR-ABL transcript ratio of 0.1% or less, was achieved by 63% of the patients with a BCR-ABL transcript ratio of 10% or less at 3 months but none of the patients who had a higher transcript ratio at this time point.

Patients with a BCR-ABL transcript ratio of 10% or less were also a significant 84% more likely to achieve long-term deep molecular remission than those with a higher transcript ratio at 3 months.

After a median on-therapy follow-up of 61.8 months, event-free survival (EFS) was significantly more common in the patients with a BCR-ABL transcript rato of 10% or lower at 3 months than those with a higher ratio, with events reporte in 12% and 63%, respectively.

Analysis indicated that a halving time threshold of 17 days was 75% specific and 92% sensitive for the discrimination of patients who would achieve molecular remission, report Carmen Fava, from the University of Turin in Italy, and co-workers.

None of the patients who had a BCR-ABL transcript ratio greater than 10% at 3 months achieved a halving time of 17 days or less, the team notes in Clinical Lymphoma, Myeloma and Leukemia.

Indeed, EFS was 96% for patients with a BCR-ABL transcript ratio of 10% or less and a halving time of 17 days or less, falling significantly to 60% for those with a BCR-ABL transcript ratio of 10% or less and a halving time over 17 days, and just 27% for those with a BCR-ABL transcript ratio greater than 10%.

The authors therefore conclude: "Our data revealed that the use of ABL as a control gene is reliable for the determination of the halving time in the clinical setting, and highlight the importance of measuring the BCR-ABL transcript at the time of CML diagnosis."



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