Fig. 12.1 Rates of treatment-free remission in the (a) STIM and (b) TWISTER clinical trials. Kaplan-Meier estimates of the proportion of patients free of molecular recurrence after imatinib withdrawal. The…
Mechanism of resistance Treatment strategies BCR-ABL1-dependent ABL1-kinase domain mutationsa Second-generation TKIs Ponatinib [77, 78] or allosteric inhibitors BCR–ABL1 amplification BCR-ABL1-independent (intrinsic) Activation of downstream signalling JAK-STAT pathway PI3K/AKT/mTOR pathway JAK2…
Imatinib Nilotinib Dasatinib Bosutinib Ponatinib First line, approved dose 400 mg OD 300 mg BID 100 mg OD NA NA Second line, approved dose 300–400 mg BID 400 mg BID 70 mg BID or 140 mg…
Time First line Second line Optimal response Failure Optimal response Failure Baseline 3 months BCR-ABLIS ≤10 % No CHR BCR-ABLIS ≤10 % No CHR or Ph+ >95 % or mutations Ph+ ≤35 % Ph+ >95 %…
Method Target Sensitivity Advantages Disadvantages Metaphase t(9;22) 1–5 % The gold standard and detection of other chromosomal changes Needs dividing cells, so generally only successful form of bone marrow sample Chromosome…
Fig. 2.1 CML stem cell maintenance. CML stem cells self-renew as HSCs do when BCR–ABL kinase activity is inhibited by tyrosine kinase inhibitors (TKIs). Therefore, survival of CML stem cells…
Reference N Response C0 (ng/mL) P value N ≤1000 N >1000 Marin et al. [10] 84 CMR 43 23.3 % 41 44.4 % 0.14 MMR 60.1 % 83.2 % 0.02 Takahashi et al. [41]…
Fig. 1.1 Clonal expansion of CML hematopoiesis. A reciprocal translocation between chromosomes 9 and 22 occurs at a hematopoietic stem cell (HSC) stage. This pre-leukemic stem cell expresses BCR-ABL at…
Anticoagulant Mode of action Plasma half-life Monitoring test(s) Therapeutic range Reversal Notes Warfarin (vitamin K antagonists) Interference with post-translational γ-carboxylation of vitamin K-dependent clotting factors 20–60 h INR 2.0–3.0, moderate…
Fig. 4.1 Example of a validation checklist 4.3 Validation Studies In the hemostasis laboratory, validation studies encompass the establishment of analytical performance expectations; calibration and calibration verification; determination of quality…
