Myelodysplastic syndrome (MDS) with isolated trisomy 8: a type of MDS frequently associated with myeloproliferative features? A report by the Groupe Francophone des Myélodysplasies

Abstract

Isolated trisomy 8 (+8) is a frequent cytogenetic abnormality in the myelodysplastic syndromes (MDS), but its characteristics are poorly reported. We performed a retrospective study of 138 MDS patients with isolated +8, classified or reclassified as MDS (excluding MDS/myeloproliferative neoplasm). Myeloproliferative (MP) features were defined by the repeated presence of one of the following: white blood cell count >10 × 10 /l, myelemia (presence of circulating immature granulocytes with a predominance of more mature forms) >2%, palpable splenomegaly. Fifty-four patients (39·1%) had MP features: 28 at diagnosis, 26 were acquired during evolution. MP forms had more EZH2 (33·3% vs. 12·0% in non-MP, P = 0·047), ASXL1 (66·7% vs. 42·3%, P = 0·048) and STAG2 mutations (77·8% vs. 21·7%, P = 0·006). Median event-free survival (EFS) and overall survival (OS) were 25 and 27 months for patients with MP features at diagnosis, versus 28 (P = 0·15) and 39 months (P = 0·085) for those without MP features, respectively. Among the 57 patients who received hypomethylating agent (HMA), OS was lower in MP cases (13 months vs. 23 months in non-MP cases, P = 0.02). In conclusion, MP features are frequent in MDS with isolated +8. MP forms had more EZH2, ASXL1 and STAG2 mutations, responded poorly to HMA, and tended to have poorer survival than non-MP forms.

Clinical significance of cytogenetic and molecular genetic abnormalities in 634 Chinese patients with myelodysplastic syndromes

“…Conflicting data exist about the impact of trisomy 8 on OS of patients with MDS. Consistent with prior reports, 15,16,18,39 we found that patients with +8 had a markedly shorter OS in comparison with those who had NK (median survival 26.8 months vs. 47.5 months, p = 0.003). The analysis of Zoe et al included 496 MDS patients with karyotypic abnormalities from the Victorian Cancer Registry and showed that +8 was identified in 93 (18.75%) patients and independently predicted shorter OS in a multivariate analysis (p = 0.024).…”

“…6,8,10 The revised international prognosis scoring system (IPSS-R) assigned +8 into the intermediate risk group. 14 However, patients with +8 are prognostically different with median overall survival (OS) from 5.9 to 26 months, [15][16][17] which is partly depending on the racial background. Median OS of patients with sole +8, varying from 32.5 to 85.9 months, are even harder to predict.…”

Asian Population Is More Prone to Develop High-Risk Myelodysplastic Syndrome, Concordantly with Their Propensity to Exhibit High-Risk Cytogenetic Aberrations

“…However, a Chinese report also indicated an association of isolated trisomy 8 with a much better prognosis, and a median survival of 44 months [29], which was higher than the Western results. A previous study disclosed that a high frequency of myeloproliferative features either at diagnosis or during evolution in MDS with isolated +8, respond poorly to hypomethylating agents (HMAs) [57]. Moreover, patients with isolated trisomy 8 present a high risk of progression to AML [26].…”

Next Generation Cytogenetics in Myeloid Hematological Neoplasms: Detection of CNVs and Translocations

“…Although trisomy 8 in MN prognosis has been related to a certain level of mosaicism in the normal population [27,28] and as an isolated alteration does not define the presence of MDS in the lack of other criteria [29], it is also an alteration classified within the intermediate prognosis group for AML and recently as an unfavorable prognosis marker in primary myelofibrosis [30]. Moreover, it has also been reported that in MDS patients presenting myeloproliferative features as well as in CMML patients, carrying trisomy 8 is linked to a worse prognosis [31,32]. Whether proliferation-related alterations have a role in the progression of the disease is something to be studied in the future.…”