Azacitidine treatment for patients with myelodysplastic syndrome and acute myeloid leukemia with chromosome 3q abnormalities

Abstract

Acute Myeloid Leukemia (AML) and myelodysplasia (MDS) with chromosome 3q abnormalities have a dismal outcome either untreated or with conventional treatments. Azacitidine (AZA) is now considered as the standard of care in high-risk MDS and oligoblastic AML patients. The objective of this study was to evaluate the impact of azacitine treatment in this cytogenetic subgroup. We report here a multicentre retrospective study of 157 patients treated with AZA for AML/MDS with chromosome 3q abnormalities and 27 patients with isolated EVI-1 overexpression. Median age was 65 years, 40 patients (25%) had inv(3)(q21q26.2) or t(3;3)(q21;q26.2), 36 patients (23%) had other balanced 3q26 rearrangements, 8 patients (5%) had balanced 3q21 rearrangements and 73 patients (46%) had other 3q abnormalities. The overall response rate was 50% (29% CR). Median overall survival was 10.6 months. By multivariate analysis, patients with lower bone marrow blast counts, higher platelet counts, non-complex cytogenetics, and absence of prior treatment with intensive chemotherapy had a better outcome. 27 patients were allo-transplanted and achieved a 21-month median OS. Balanced 3q21 translocations were associated with a better response rate and overall survival. Outcome of patients with isolated EVI-1 overexpression was comparable to that of patients with chromosome 3q lesions. Thus, AML/MDS patients with 3q abnormalities appear to be a heterogeneous group in their response to AZA, and AZA may represent a suitable option in particular as a bridge to allogeneic transplantation.

Cytogenetic, Inflammatory, Immunologic, and Infectious Basis for Dysplastic Hematopoeisis

“…The observation that dysplastic myeloid features are retained in different maturation stages in MDS patients suggests a potential hierarchical model for dysplastic hematopoeisis (see harbored similar mutations found in leukemic cells. This mutation were observed at lower allele frequencies (4-31%), 20 suggesting a multipotent stem cell disease initiating effect. 21 These mutations, originated in the HSC compartment, can clonally expand and progress as preleukemic fractions, contribute to acute AML, an evolving concept that highlights a hierarchical model for MDS.…”

Efficacy of Azacitidine in autoimmune and inflammatory disorders associated with myelodysplastic syndromes and chronic myelomonocytic leukemia

“…The SNFMI registry included 123 MDS/CMML patients with AID in 26 centres) [13], while the GFM registry included 4202 MDS/CMML in 30 centres of whom 80 also had documented AID. The GFM registry has been so far the basis for many publications of the GFM or that included the GFM [14][15][16].…”

Low-intensity regimens versus standard-intensity induction strategies in acute myeloid leukemia

“…36 This effect is particularly seen in those with chromosome 3q abnormalities, which are associated with resistance to conventional chemotherapy and for which azacitidine has been shown to be effective. 37 Several studies have suggested that gene mutations can impact prognosis, such as TET2, which was associated with increased survival after treatment with azacitidine, 38 DNMT3A with improved response after treatment with decitabine, 39 and TP53 with improved response after treatment with a 10-day schedule of decitabine. 40 Guadecitabine is a hypomethylating dinucleotide of decitabine linked to guanosine.…”