title: Estimation of current cumulative incidence of leukaemia-free patients and current leukaemia-free survival in chronic myeloid leukaemia in the era of modern pharmacotherapy.
abstract: BACKGROUND
  The current situation in the treatment of chronic myeloid leukaemia (CML) presents a new challenge for attempts to measure the therapeutic results, as the CML patients can experience multiple leukaemia-free periods during the course of their treatment. Traditional measures of treatment efficacy such as leukaemia-free survival and cumulative incidence are unable to cope with multiple events in time, e.g. disease remissions or progressions, and as such are inappropriate for the efficacy assessment of the recent CML treatment.
  
  
  METHODS
  Standard nonparametric statistical methods are used for estimating two principal characteristics of the current CML treatment: the probability of being alive and leukaemia-free in time after CML therapy initiation, denoted as the current cumulative incidence of leukaemia-free patients; and the probability that a patient is alive and in any leukaemia-free period in time after achieving the first leukaemia-free period on the CML treatment, denoted as the current leukaemia-free survival. The validity of the proposed methods is further documented in the data of the Czech CML patients consecutively recorded between July 2003 and July 2009 as well as in simulated data.
  
  
  RESULTS
  The results have shown a difference between the estimates of the current cumulative incidence function and the common cumulative incidence of leukaemia-free patients, as well as between the estimates of the current leukaemia-free survival and the common leukaemia-free survival. Regarding the currently available follow-up period, both differences have reached the maximum (12.8% and 20.8%, respectively) at 3 years after the start of follow-up, i.e. after the CML therapy initiation in the former case and after the first achievement of the disease remission in the latter.
  
  
  CONCLUSIONS
  Two quantities for the evaluation of the efficacy of current CML therapy that may be estimated with standard nonparametric methods have been proposed in this paper. Both quantities reliably illustrate a patient's disease status in time because they account for the proportion of patients in the second and subsequent disease remissions. Moreover, the model is also applicable in the future, regardless of what the progress in the CML treatment will be and how many treatment options will be available, respectively.
authors: Institute of Biostatistics and Analyses, Department of Mathematics and Statistics, Masaryk University, Brno, Czech Republic.
authors: Tomáš
authors: T
authors: Pavlík
authors: Eva
authors: E
authors: Janoušová
authors: Zdeněk
authors: Z
authors: Pospíšil
authors: Jan
authors: J
authors: Mužík
authors: Daniela
authors: D
authors: Záčková
authors: Zdeněk
authors: Z
authors: Ráčil
authors: Hana
authors: H
authors: Klamová
authors: Petr
authors: P
authors: Cetkovský
authors: Marek
authors: M
authors: Trněný
authors: Jiří
authors: J
authors: Mayer
authors: Ladislav
authors: L
authors: Dušek
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D003198:Computer Simulation; D018153:Czech Republic / Q000453:epidemiology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D010879:Piperazines / Q000627:therapeutic use*; D015995:Prevalence; D011743:Pyrimidines / Q000627:therapeutic use*; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate