Flow Cytometry based automatic MRD assessment in Acute Lymphoblastic Leukaemia: Longitudinal evaluation of time-specific cell population models

Acute Lymphoblastic Leukaemia (ALL) is a disease induced by genetic lesion of blood progenitor cells, which influences the hematopoiesis, resulting in the proliferation of undifferentiated (leukaemic) cells. The Minimal Residual Disease (MRD) value is used to quantify these cells and is reliably assessable using Flow CytoMetry (FCM) based measurements. It is a powerful predictor for treatment response and thus used as diagnostic tool for planning patient's individual therapy. In this work we propose an evaluation scheme for longitudinal disease stadium dependent MRD assessment performed on collected clinical data of B-ALL cases after 15, 33 and 78 days of therapy, guided according to the standardised AIEOP-BFM2009 treatment protocol. We compare the blast classification performance using time-specific population models, which are trained using two different core approaches: generative and discriminative. The results show that cell populations change dependent on the observed treatment day and it is identified that a time-specific model of day 15 is not suitable to estimate leukaemic cell populations at treatment day 33 and 78, independent of the methodologies evaluated.