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Type: Journal article
Title: Long-term treatment-free remission of chronic myeloid leukemia with falling levels of residual leukemic cells
Author: 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.
Citation: Leukemia, 2018; 32(12):2572-2579
Publisher: Springer Nature
Issue Date: 2018
ISSN: 0887-6924
Statement of
David M. Ross, Ilaria S. Pagani, Naranie Shanmuganathan, Chung H. Kok, John F. Seymour, Anthony K. Mills, Robin J. Filshie, Christopher K. Arthur, Phuong Dang, Verity A. Saunders, Jodi Braley, Agnes S. Yong, David T. Yeung, Deborah L. White, Andrew P. Grigg, Anthony P. Schwarer, Susan Branford, Timothy P. Hughes, On behalf of the Australasian Leukaemia and Lymphoma Group (ALLG)
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 MR⁴·⁵). 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 MR⁵·⁰ in the first year of TFR to MR⁶·¹ 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.
Keywords: Australasian Leukaemia and Lymphoma Group (ALLG)
Rights: © Springer Nature Limited 2018
DOI: 10.1038/s41375-018-0264-0
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