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Deletion of the long arm of chromosome 5 [del(5q)] is the most prevalent cytogenetic abnormality in patients with Myelodysplastic Syndrome (MDS) and is frequently associated with good prognosis. However, MDS with del(5q) is a heterogeneous entity in terms of survival and/or progression to Acute Myeloid Leukemia (AML). The analysis of the proposed Revised International Prognostic Scoring System (R-IPSS) for MDS reinforces the importance of blast count, karyotype and number and degree of cytopenias to define high-risk subgroups with worse prognosis. More recently, the presence of TP53 mutation and/or high P53 protein expression by immunohistochemistry (IHC) has been proposed as additional markers of poorer outcome in MDS with chromosome 5 abnormalities.

Assess the prognostic impact of blast count, number of additional cytogenetic abnormalities, transfusion dependency and p53 IHC expression, in MDS with del(5q).

We retrospectively analyzed 18 patients diagnosed with MDS and del(5q) at our centre, between 2005-2014, in which a bone marrow histology was available. All patients were evaluated for R-IPSS, transfusion dependency and P53 protein expression by bone marrow IHC. A high blast count was defined by the presence of >5% of blasts cells in bone marrow smear. A high number of chromosome abnormalities was defined by >=2 abnormalities besides del(5q). A positive p53 IHC expression was defined by the presence of >5% p53 positive cells observed on the histology of bone marrow. Transfusion dependency was defined as no period of eight consecutive weeks without red blood cell (RBC) transfusions.

The median of age was 69 (55-81) years and 11 (61%) patients were male. The MDS WHO-classification was: RCMD n=3 (16,7%), RAEB-1 n=3 (16,7%), RAEB-2 n=5 (27,8%) and MDS with isolated del(5q) n=7 (38,9%). In terms of R-IPSS evaluation, patients were stratified as: Very Low n=1 (5,6%), Low n=6 (33,3%), Intermediate n=2 (11,1%), High n=2 (11,1%) and Very High n=7 (38,9%). For the relevant prognostic parameters analyzed, frequencies were: n=8 (44,4%) had >5% of blasts, n=4 (22,2%) had >=2 chromosome abnormalities besides del(5q), n=16 (88,9%) had transfusion dependency and n=9 (50%) had >5% of p53 IHC protein expression. Overall Survival (OS) and Progression to AML Free Survival (PFS) were significantly worse for patients with >5% of blast count (OS: 5 months vs 39 months, p<0.05; PFS: 5 months vs 32 months, p>0.05) and for those with >=2 chromosome abnormalities besides del(5q)(OS: 6 months vs 36 months, p<0.05; PFS: 5 months vs 29 months, p<0.05). Those differences were also observed in multivariate analysis (p<0.05). A trend towards a worse OS and PFS was observed for transfusion dependency (OS: 21 months vs 48 months, p=0.18; PFS: 17 months vs 44 months, p=0.12) and >5% of p53 IHC protein expression (OS: 19 months vs 30 months, p=0.37; PFS: 18 months vs 21 months, p=0.75).

The presence of a high blast count and other chromosome abnormalities besides del(5q) define subsets of worse prognosis in MDS with del(5q), despite of this being classically considered a chromosomal abnormality associated with good prognosis. There is also a trend for a poor prognosis in patients with transfusion dependency and positive p53 IHC protein expression. The absence of a statistical significant difference in OS and PFS for these patients subsets might be due to the low number of patients in this cohort.