Long-term treatment-free remission of chronic myeloid leukemia with falling levels of residual leukemic cells. Issue 12 (December 2018)

• Record Type: Journal Article
• Authors: Ross, David; Pagani, Ilaria; Shanmuganathan, Naranie; Kok, Chung; Seymour, John; Mills, Anthony; Filshie, Robin; Arthur, Christopher; Dang, Phuong; Saunders, Verity; Braley, Jodi; Yong, Agnes; Yeung, David; White, Deborah; Grigg, Andrew; Schwarer, Anthony; Branford, Susan; Hughes, Timothy
• Is Part Of: Leukemia. Volume 32:Issue 12(2018)
• Page Start: 2572
• Page End: 2579
• Publication Date: 2018-12
• Subjects: Leukemia -- Periodicals; 616.99419
• DOI: 10.1038/s41375-018-0264-0
• Languages: English
• ISSNs: 0887-6924

Abstract

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 undetectableBCR-ABL1 mRNA (approximately MR4.5 ). Molecular relapse was defined as detectableBCR-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 individualizedBCR-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.