Management of Chronic Myeloid Leukemia in Advanced Phase

Abstract

Management of chronic myeloid leukemia (CML) in advanced phases remains a challenge also in the era of tyrosine kinase inhibitors (TKIs) treatment. Cytogenetic clonal evolution and development of resistant mutations represent crucial events that limit the benefit of subsequent therapies in these patients. CML is diagnosed in accelerated (AP) or blast phase (BP) in <5% of patients, and the availability of effective treatments for chronic phase (CP) has dramatically reduced progressions on therapy. Due to smaller number of patients, few randomized studies are available in this setting and evidences are limited. Nevertheless, three main scenarios may be drawn: (a) patients diagnosed in AP are at higher risk of failure as compared to CP patients, but if they achieve optimal responses with frontline TKI treatment their outcome may be similarly favorable; (b) patients diagnosed in BP may be treated with TKI alone or with TKI together with conventional chemotherapy regimens, and subsequent transplant decisions should rely on kinetics of response and individual transplant risk; (c) patients in CP progressing under TKI treatment represent the most challenging population and they should be treated with alternative TKI according to the mutational profile, optional chemotherapy in BP patients, and transplant should be considered in suitable cases after return to second CP. Due to lack of validated and reliable markers to predict blast crisis and the still unsatisfactory results of treatments in this setting, prevention of progression by careful selection of frontline treatment in CP and early treatment intensification in non-optimal responders remains the main goal. Personalized evaluation of response kinetics could help in identifying patients at risk for progression.

Focal blast crisis in concomitant myelodysplastic syndrome and chronic myelogenous leukemia

“…The best management of a blast crisis, and by proxy MS associated with CML, is to attain an prompt and considerable reduction and elimination of detectable BCR/ABL1 with TKIs, when possible [ 10 , 11 ]. In fit individuals, treatment with AML-type induction chemotherapy is felt to be standard.…”

Development of BCR-ABL1 Transgenic Zebrafish Model Reproducing Chronic Myeloid Leukemia (CML) Like-Disease and Providing a New Insight into CML Mechanisms

“…The CML natural progression is characterized by hyper-leukocytosis in peripheral blood and bone marrow with a prevalence of granulocytes and myeloid cells at different steps of maturation. The percentage of blast cells is less than 2% during the so-called CML chronic phase and progressively rise in the following accelerated and blastic phases [ 78 , 79 , 80 ]. To evaluate the presence of similar alterations in circulating blood cells, we investigated both the blood cells and the hematopoietic organs of our transgenic model.…”

Digital PCR: A Reliable Tool for Analyzing and Monitoring Hematologic Malignancies

“…This fusion gene is then translated into a BCR-ABL1 oncoprotein that triggers neoplastic transformation of the hematopoietic stem cell. CML is one of the first malignancies for which the principle of targeted therapy has been successfully applied thanks to the use of tyrosine kinase inhibitors (TKI) [90,91]. The Europe Against Cancer (EAC) qPCR assay has some inherent limitations, such as the low accuracy at the lower end of the calibration curve, as well as inter-laboratory discrepancies in assay execution.…”