Abstract
High-risk Myelodysplastic syndromes (MDS) represent therapeutical challenges and are usually managed with hypomethylating agents such as azacitidine. Given the lack of data in the literature concerning azacitidine effects on bone marrow, we retrospectively analyzed 57 high-risk MDS cases in order to identify any changes induced by azacitidine therapy or relevant correlations between therapy response and pre- or post-treatment features. Azacitidine treatment had no significant impact on bone marrow cellularity or morphological dysplastic features. On the contrary, although not statistically significant, we observed a slight decrease in CD34+ and CD117+ blasts and p53+ precursors after treatment. Moreover, pre-treatment IPSS-R cytogenetic score (p = 0.004), lymphocytic infiltrate (p = 0.017) and p53+ elements (p = 0.001) correlated with AML progression; pre-treatment lymphocytic infiltrate was also linked to better response to therapy (p = 0.004), suggesting an anti-tumoral role of bone marrow microenvironment. Post-treatment blast count impacted negatively on overall survival (p = 0.035) and risk of leukemic progression (p = 0.04), while both post-treatment lymphocytic infiltrate and p53+ elements showed significant correlation with treatment response (p = 0.004 and p = 0.003 respectively). Higher post-treatment p53+ elements correlated also with risk of leukemic progression (p = 0.013). Our results suggest the possible role of lymphocytic infiltrate and p53+ elements as predictive markers in MDS treated with azacitidine, disclosing new chapters in the understanding of MDS evolution and treatment.
Highlights
While low-risk Myelodysplastic syndromes (MDS) have a better prognosis and can be clinically managed with approaches varying from active surveillance to erythropoiesis-stimulating agents, current treatment of high-risk MDS, whose life expectancy is inferior to two years, is essentially based either on hypomethylating agents or intensive chemotherapy
Despite the wide usage of hypomethylating agents and especially of azacitidine in MDS, little is known about the morphological and immunophenotypical modifications induced by treatment on bone marrow cellularity, some studies have focused on the effects of azacitidine on single cellular compartments, such as mesenchymal stem cells [11]
At the time of diagnosis, most cases belonged to the World Health Organization (WHO) category of myelodysplastic syndromes with excess blasts (53/57, 93% of cases, with 41/53, 77% represented by MDS-EB type 2), with a minority (4/57, 7% of cases) diagnosed as myelodysplastic syndrome with multilineage dysplasia
Summary
Despite the wide usage of hypomethylating agents and especially of azacitidine in MDS, little is known about the morphological and immunophenotypical modifications induced by treatment on bone marrow cellularity, some studies have focused on the effects of azacitidine on single cellular compartments, such as mesenchymal stem cells [11]. Of high-risk MDS patients, reducing the number of CD34+ blasts and restoring myeloid or monocytic pattern maturation in a smaller subset of cases. This immunophenotypic improvement proved to be linked to better clinical response. Our main purpose was to evaluate bone marrow comprehensive features in patients with MDS before and after treatment with azacitidine, in order to assess the relevance of modifications induced by therapy. We focused on the retrospective correlation between response to azacitidine and histological and immunophenotypic features of bone marrow biopsies, in order to evaluate putative predictive factors of response to hypomethylating agents
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