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Title: Long-term treatment-free remission of chronic myeloid leukemia with falling levels of residual leukemic cells.
Austin Authors: Ross, David M;Pagani, Ilaria S;Shanmuganathan, Naranie;Kok, Chung H;Seymour, John F;Mills, Anthony K;Filshie, Robin J;Arthur, Christopher K;Dang, Phuong;Saunders, Verity A;Braley, Jodi;Yong, Agnes S;Yeung, David T;White, Deborah L;Grigg, Andrew P ;Schwarer, Anthony P ;Branford, Susan;Hughes, Timothy P
Affiliation: Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
School of Paediatrics, Faculty of Health Sciences, University of Adelaide, Adelaide, Australia
Department of Clinical Haematology, Austin Health, Heidelberg, Victoria, Australia
Department of Haematology, St Vincent's Hospital, Melbourne, Australia
School of Biological Sciences, Faculty of Sciences, University of Adelaide, Adelaide, Australia
Cancer Theme, South Australian Health & Medical Research Institute, Adelaide, Australia
School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, Australia
Australasian Leukaemia and Lymphoma Group, Melbourne, Australia
Department of Haematology, Royal North Shore Hospital, Sydney, Australia
Health Sciences UniSA, Adelaide, Australia
Genetic and Molecular Pathology, Centre for Cancer Biology, SA Pathology, Adelaide, Australia
Department of Haematology, The Alfred Hospital and Box Hill Hospital, Melbourne, Australia
School of Pharmacy and Medical Science, University of South Australia, Adelaide, Australia
Department of Haematology, Royal Adelaide Hospital and SA Pathology, Adelaide, Australia
Flinders University and Medical Centre, Adelaide, Australia
Department of Haematology, Royal Melbourne Hospital and Peter MacCallum Centre, and University of Melbourne, Melbourne, Australia
Division of Cancer Services, Princess Alexandra Hospital, Brisbane, Australia
Issue Date: 2018
Date: 2018-10-12
Publication information: Leukemia 2018; 32(12): 2572-2579
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.
DOI: 10.1038/s41375-018-0264-0
ORCID: 0000-0001-7171-2935
Journal: Leukemia
PubMed URL: 30315232
Type: Journal Article
Appears in Collections:Journal articles

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