Monosomal karyotype in MDS: explaining the poor prognosis?

Abstract

Monosomal karyotype (MK) is associated with an adverse prognosis in patients in acute myeloid leukemia (AML). This study analyzes the prognostic impact of MK in a cohort of primary, untreated patients with myelodysplastic syndromes (MDS). A total of 431 patients were extracted from an international database. To analyze whether MK is an independent prognostic marker in MDS, cytogenetic and clinical data were explored in uni- and multivariate models regarding overall survival (OS) as well as AML-free survival. In all, 204/431 (47.3%) patients with MK were identified. Regarding OS, MK was prognostically significant in patients with ≤ 4 abnormalities only. In highly complex karyotypes (≥ 5 abnormalities), MK did not separate prognostic subgroups (median OS 4.9 months in MK+ vs 5.6 months in patients without MK, P=0.832). Based on the number of abnormalities, MK-positive karyotypes (MK+) split into different prognostic subgroups (MK+ and 2 abnormalities: OS 13.4 months, MK+ and 3 abnormalities: 8.0 months, MK+ and 4 abnormalities: 7.9 months and MK+ and ≥ 5 abnormalities: 4.9 months; P<0.01). In multivariate analyses, MK was not an independent prognostic factor. Our data support the hypothesis that a high number of complex abnormalities, associated with an instable clone, define the subgroup with the worst prognosis in MDS, independent of MK.

Specific abnormalities versus number of abnormalities and cytogenetic scoring systems for outcome prediction after allogeneic hematopoietic SCT for myelodysplastic syndromes

“…In line with our findings, recent studies have questioned the relative importance of MK in MDS and secondary AML (sAML) as compared with burden of cytogenetic complexity. [18][19][20][21][22][23] IPSS-R cytogenetic classification predicted OS more efficiently than IPSS cytogenetic classification, a finding consistent with those of a larger series of MDS/sAML patients who underwent HCT 10 ( Table 6), suggesting that IPSS-R cytogenetic classification may indeed refine prognosis not only in untreated patients but also after HCT. In addition, IPSS-R cytogenetic classification as a five-group score, but not MK, was predictive of increased CIR, possibly as a result of the additional impact of 3q21q26 and del 7q found within non-MK (60% in each case).…”

Predictive factors for the outcome of allogeneic transplantation in patients with MDS stratified according to the revised IPSS-R

“…20 The recently developed MDS cytogenetic scoring system showed a significant effect on overall survival and on probability of relapse of patients with MDS or oligoblastic AML receiving an allogeneic HSCT. 21,32 The presence of MK, which was not considered as a separate category by the MDS cytogenetic scoring system, 33 has emerged as a further risk factor for worse prognosis in myeloid neoplasms and was associated with a poor outcome after transplantation. 26,32,34 MK frequently involves chromosome 5 and 7 abnormalities and also TP53 gene mutations that are significant risk factors for disease relapse after allogeneic HSCT.…”

Absence of aberrant myeloid progenitors by flow cytometry is associated with favorable response to azacitidine in higher risk myelodysplastic syndromes

“…The response criteria were based on IWG2006 criteria. 12 The FCSS is significantly decreased in patients with CR compared with patients with PD after 3 cycles of azacitidine (p=0.004). MDS treated with azacitidine.…”

“…Diagnosis were made according to WHO2008 classification (11). MDS patients were assigned into prognostic groups by applying the IPSS and an adjusted IPSS with extra weight to poor risk cytogenetics (2,12). Bone marrow samples were evaluated for chromosomal anomalies according to International System for Human Cytogenetic Nomenclature guidelines (13).…”