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Some mathematical models assume leukaemia stem cells are insensitive to TKI-therapy. Displayed curves are adapted from previously published examples [ 7 ]. D Once median durations of DMR surpass 30 months, cohorts with longer median durations of DMR have only slightly lower TFR failure rates compared to those with shorter median durations of DMR Table 1 [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ].
Slopes were calculated by least-squares regression with each data point having the same weight. However, there are contradictory data [ 12 ]. Data from the Japanese survivors of A-bombs who had blood analyses biennially beginning in s are informative about leukaemia latency post-exposure [ 25 ]. There were 33 excess cases of CML β attributable to exposure to the A-bomb radiations [ 26 ]. These data imply a wide range of latency from one leukaemia stem cell to diagnosis of CML.
The premise that substantial depletion of leukaemia stem cells is a pre-requisite for long-term TFR is an unproven assumption. Such a person could be operationally cured , relapse at a later time or die of something else before CML recurrence. Only time would tell. The proper calculus to account for everyone with CML follows. It should be emphasized that MR 4 can be lost and regained, especially in those remaining in MMR [ 14 , 17 , 21 ].
Therefore, TFR might be delayed, but not prevented, in at least some of these 87 persons. Our calculation represents a worst-case scenario. Note that in our calculations all subjects begin after achieving 1 year of DMR. However, this assumption is questionable when we examine the scope of published data. These data indicate the TFR failure rate declines very slowly β0.
