Maintenance Therapy of Childhood ALL - Longitudinal Prifiles of Blood Counts and their association

Resume: Acute lymphoblastic leukemia is the most common   cancer among children aged 1 to 15 years. The treatment consists of three parts, where the   maintenance therapy (the last part) is the longest part of the treatment. During maintenance therapy,   doses of oral chemotherapy are adjusted in response to frequent measurements   of white blood counts (WBC), absolute neutrophile count

(ANC) and absolute lymphocyte count (ALC). Currently   there exists no general guidelines for how the doses of the drugs are adjusted optimally. In   the Nordic countries doses are adjusted according to white blood count (WBC). However, this is not   associated with the risk of relapse, but instead ANC has turned out to be associated with the risk of   relapse. Due to this nding it is currently discussed whether ANC should be used for dose   adjustment instead of WBC. In this thesis, we use a large data set to examine   the longitudinal proles for WBC, ANC and ALC during maintenance therapy.

The purpose is to see whether these blood counts   share some of the same features as well as to determine their association. In   the context of linear mixed models, we consider univariate models for each   outcome to examine each of the proles. To investigate the correlation and to compare proles, the univariate mixed models are combined in a   multivariate model. With several outcomes, the parameters in the multivariate   model cannot be estimated because of a large number of random
  ects, but instead a pairwise modelling strategy based on pseudo-likelihoods  is implemented. We find some differences in subgroups with respect to   their longitudinal profiles. Furthermore, the profiles for the blood counts share some, but not   all, features. In particular we find that the process-ses do not run in   parallel. ANC is constant in the maintenance therapy, whereas WBC and ALC   decreases. Moreover, we find that WBC and ANC are highly correlated with a   correlation of approximately 0.8, the correlation between WBC and ALC is   moderate (approximately 0.4), whereas the correlation between ANC and ALC is   low (approximately 0.1).