Long-term treatment-free remission of chronic myeloid leukemia with falling levels of residual leukemic cells.

David Ross, Ilaria Pagani, Naranie Shanmuganathan, Chung Kok, John Seymour, Anthony Mills, Robin Filshie, Christopher Arthur, Phuong Dang, Verity Saunders, Jodi Braley, Agnes Yong, David Yeung, Deborah White, Andrew Grigg, Anthony Schwarer, Susan Branford, Timothy Hughes

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Following the achievement of deep molecular response on tyrosine kinase inhibitors (TKIs), approximately half of patients with chronic myeloid leukemia (CML) can discontinue TKI and remain in treatment-free remission (TFR). The ALLG CML8 study enrolled 40 imatinib-treated patients with undetectable BCR-ABL1 mRNA (approximately MR 4.5 ). Molecular relapse was defined as detectable BCR-ABL1 on two consecutive tests or any single value >0.1%. With a median follow-up of 8.6 years (range 5.7–11.2 years), 18 patients remain in continuous TFR (45.0%; 95% confidence interval 31.9−63.4%). The latest relapse detected was 27 months after stopping imatinib. No patient progressed to advanced phase. Twenty-two patients met criteria for imatinib re-treatment and all regained undetectable molecular response. Nine patients in long-term TFR were monitored by highly sensitive individualized BCR-ABL1 DNA PCR in a sufficient number of samples to enable more precise quantification of residual leukemia. BCR-ABL1 DNA decreased from a median of MR 5.0 in the first year of TFR to MR 6.1 in the sixth year of TFR. Our results support the long-term safety and remarkable stability of response after imatinib discontinuation in appropriately selected CML patients. Serial high sensitivity testing provides a new and unexpected finding of gradually reducing CML cells in patients in long-term TFR.

Original languageEnglish
Pages (from-to)2572-2579
Number of pages8
JournalLeukemia
Volume32
Issue number12
DOIs
Publication statusPublished - 2018

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    Ross, D., Pagani, I., Shanmuganathan, N., Kok, C., Seymour, J., Mills, A., Filshie, R., Arthur, C., Dang, P., Saunders, V., Braley, J., Yong, A., Yeung, D., White, D., Grigg, A., Schwarer, A., Branford, S., & Hughes, T. (2018). Long-term treatment-free remission of chronic myeloid leukemia with falling levels of residual leukemic cells. Leukemia, 32(12), 2572-2579. https://doi.org/10.1038/s41375-018-0264-0