INFLUENCE OF ACUTE MYELOID LEUKEMIA PROGRESSION ON THE PROGNOSIS OF PATIENTS WITH MYELODYSPLASTIC SYNDROMES

GONZALEZ J; KORNBLIHTT L; LARRIPA I; BESTACH Y; ALFONSO G; ALBERBIDE J; ENRICO A; BASQUIERA AL; LAZZARINO C; BELLI C

ACUTE MYELOID LEUKAEMIA (AML): SYMPTOMS, DIAGNOSIS AND TREATMENT

Nova Biomedical Books, Nova Science Publishers

Lugar: New York; Año: 2018; p. 43 - 172

Myelodysplastic Syndromes (MDS) are a challenging group of clonal disorders with a highly variable behavior. The clinical course may range from stable disease over 10 years to death within a few months due to complications associated with their cytopenias or transformation to Acute Myeloid Leukemia (AML). Once this progression occurs, the prognosis is dismal with an extremely poor outcome and a short survival. In our series of 901 (510 patients from the Argentine MDS Registry) patients with de novo MDS, 168 (19%) progressed to AML with a median overall survival of 18.0 months from diagnosis and of 3.4 months after progression. The analysis of 389 age-related events indicated that AML-related events decreased with age from 65% in the patients younger than 50 years old to 33% in patients older than 80.Various scoring systems based on clinical characteristics at presentation have been designed to define prognostic subgroups, including the International Prognostic Scoring System (IPSS), which has been revised (IPSS-R), and the WHO-based Prognostic Scoring System (WPSS). In our series, almost all of the prognostic variables and scoring systems were significantly associated with AML-development time. Also, the vast majority of the parameters analyzed indicated that patients without evolution to AML displayed a longer median overall survival than those who progressed. Nevertheless, the survival of patients with adverse karyotypes, >10% of bone marrow blasts, or, therefore, with high risk was not affected upon comparison of patients with or without evolution to AML. We could also observe a significant concordance between the IPSS-R and WPSS, mainly identifying lower- and higher-risk patients. As expected, the survival of higher-risk patients, according to both systems or of those who upgraded to a higher WPSS, was unaffected by their evolution to AML. In other words, higher-risk patients are going to die, within a median time of 2 years, from causes intrinsic to the disease that are directly related to their bone marrow failure, with or without leukemic evolution. However, leukemic evolution did affect survival when other combinations were analyzed. Those who sustained their low, intermediate or upgraded to an intermediate WPSS risk and evolved to AML are going to live 6.1, 3.3 or 2.9 times shorter, being younger than those who died of non-AML related causes.Prognostic characterization of individual patients is vital prior initiating treatment based on the great variability in the outcome of MDS. The main objective in higher-risk patients is to extend the survival trying to modify the natural history of the disease. The use of IPSS-R and WPSS systems simultaneously may help pointing out those patients that would require a more aggressive treatment; nevertheless, more efforts are needed to identify of those lower-risk patients whose survival is significantly reduced by AML progression.This chapter thus evaluates different prognostic factors and stratifications of risk that have been published in the attempt to access the influence of AML progression on the overall survival of MDS patients evaluating them in our population based registry. Also, currently therapeutic approaches for higher risk MDS have been reviewed.