ABSTRACT
We aimed to characterize withdrawal syndrome (WS) and evaluate factors associated with its development in the prospective clinical study RU-SKI in patients with chronic myeloid leukemia with deep molecular response who discontinued tyrosine kinase inhibitor (TKI) therapy. In total, 98 adult patients with chronic myeloid leukemia chronic phase, TKI therapy ≥ 3 years, and deep molecular response (BCR-ABL ≤ 0.01%) ≥ 2 years were enrolled and observed without treatment. WS was defined as newly observed or worsening musculoskeletal pain after TKI cessation. WS symptoms were found in 41 (42%) of 98 patients with a median time of observation of 25 months (range, 12-42 months). WS grades 1 to 2 and grade 3 were observed in 39 (95%) and in 2 (5%) patients, respectively. The median duration of WS was 5 months (range, 1-25 months). WS was resolved in 37 (90%) patients. Anti-inflammatory therapy was used in 21 (51%) patients. Older age (P = .039) and longer TKI therapy (P = .001) were associated with WS. The 2-month landmark analysis found no association of WS development and the rate of molecular relapses. In total, 42% of the patients experienced WS after TKI therapy discontinuation in the RU-SKI study. Physicians should be warned about the possibility of WS development, and patients of older age and with longer TKI treatment need special attention.
Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Protein Kinase Inhibitors/administration & dosage , Substance Withdrawal Syndrome , Adult , Aged , Aged, 80 and over , Female , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/physiopathology , Male , Middle Aged , Prospective Studies , Recurrence , Russia , Substance Withdrawal Syndrome/metabolism , Substance Withdrawal Syndrome/pathology , Substance Withdrawal Syndrome/physiopathologyABSTRACT
I report a novel BCR-ABL point mutation c.844G>C p.E282Q and a case of combination of two BCR-ABL point mutations (p.E282Q and p.L298R) and exon 7 deletion (del. c.1086-1270) in TKI-resistant patient. These point mutations were present only in a truncated transcript and were absent in "wild-type" BCR-ABL transcript.
