# CCI and CLFS as current survival measures in CML

Nowadays, with the possibility of treating chronic myeloid leukaemia (CML) patients with sequential tyrosine kinase inhibitor (TKI) therapy, the remission state in CML can be achieved repeatedly. Thus, the CML patient’s disease course can be seen as a series of disease remissions and subsequent relapses (Figure 1).

*Figure 1. Block scheme of sequence of possible events in CML patient’s disease course*

The aim of the outcome assessment in CML patients is to quantify the probability of being in disease remission (state 3) in time. Therefore, the standard ways of patient outcome assessment such as the common leukaemia-free survival (LFS) and cumulative incidences (CIs) are no longer appropriate for such quantification as they are unable to cope with multiple remissions. Two current survival measures were proposed by Pavlik et al. (2011) to overcome this problem:

- CCI is the probability that a patient is alive and in any disease remission after initiating his or her TKI therapy.
- CLFS is the probability that a patient is alive and in any disease remission after achieving the first disease remission. It should be noted that only patients who achieved at least first disease remission are available for the CLFS estimation.

An example of the current and common survival measures is in Figure 2. The figure indicates that the CI curve overestimates the probability of being alive and in remission after initiating the therapy and the LFS underestimates the probability of being alive and in remission after the achievement of first remission on the therapy. On the contrary, the CCI and CLFS curves illustrate a CML patient’s disease status in time more reliably as they account for multiple disease remissions.

*Figure 2. An example of the current and common survival estimates with 95% point-wise bootstrap confidence intervals*

The current survival measures can be used not only for the descriptive analyses of patient’s disease course and CML treatment outcome but also for stratified analyses (Fig 3) and research on prognostic factors. Moreover, the current survival measures are also applicable in the future, regardless of the progress in the CML treatment and how many treatment options will be available.

*Figure 3. An example of stratified CCI and CLFS curves*

For more details, please see the following papers:

- Pavlik, T., Janousova, E., Pospisil, Z., et al. Estimation of current cumulative incidence of leukaemia-free patients and current leukaemia-free survival in chronic myeloid leukaemia in the era of modern pharmacotherapy. BMC Medical Research Methodology 2011, 11: 140.
- Pavlik, T., Janousova, E., Mayer, J., et al. Current survival measures reliably reflect modern sequential treatment in CML: Correlation with prognostic stratifications. American Journal of Hematology 2013, 88(9):790-7.