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Leukemia. 2018 Dec;32(12):2572-2579. doi: 10.1038/s41375-018-0264-0. Epub 2018 Oct 12.

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

Author information

1
Cancer Theme, South Australian Health & Medical Research Institute, Adelaide, Australia. David.Ross@sa.gov.au.
2
Department of Haematology, Royal Adelaide Hospital and SA Pathology, Adelaide, Australia. David.Ross@sa.gov.au.
3
School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, Australia. David.Ross@sa.gov.au.
4
Flinders University and Medical Centre, Adelaide, Australia. David.Ross@sa.gov.au.
5
Australasian Leukaemia and Lymphoma Group, Melbourne, Australia. David.Ross@sa.gov.au.
6
Cancer Theme, South Australian Health & Medical Research Institute, Adelaide, Australia.
7
School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, Australia.
8
Australasian Leukaemia and Lymphoma Group, Melbourne, Australia.
9
Department of Haematology, Royal Adelaide Hospital and SA Pathology, Adelaide, Australia.
10
Genetic and Molecular Pathology, Centre for Cancer Biology, SA Pathology, Adelaide, Australia.
11
School of Pharmacy and Medical Science, University of South Australia, Adelaide, Australia.
12
Department of Haematology, Royal Melbourne Hospital and Peter MacCallum Centre, and University of Melbourne, Melbourne, Australia.
13
Division of Cancer Services, Princess Alexandra Hospital, Brisbane, Australia.
14
Department of Haematology, St Vincent's Hospital, Melbourne, Australia.
15
Department of Haematology, Royal North Shore Hospital, Sydney, Australia.
16
School of Biological Sciences, Faculty of Sciences, University of Adelaide, Adelaide, Australia.
17
School of Paediatrics, Faculty of Health Sciences, University of Adelaide, Adelaide, Australia.
18
Health Sciences UniSA, Adelaide, Australia.
19
Department of Clinical Haematology, Austin Hospital and Olivia Newton John Cancer Research Institute, Melbourne, Australia.
20
Department of Haematology, The Alfred Hospital and Box Hill Hospital, Melbourne, Australia.

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.

PMID:
30315232
DOI:
10.1038/s41375-018-0264-0

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