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Clinical Trial
. 2013 Oct;88(10):831-7.
doi: 10.1002/ajh.23513. Epub 2013 Jul 23.

Acquisition of cytogenetic abnormalities in patients with IPSS defined lower-risk myelodysplastic syndrome is associated with poor prognosis and transformation to acute myelogenous leukemia

Elias Jabbour  1 , Koichi Takahashi, Xuemei Wang, A Megan Cornelison, Lynne Abruzzo, Tapan Kadia, Gautam Borthakur, Zeev Estrov, Susan O'Brien, Mar Mallo, William Wierda, Sherry Pierce, Yue Wei, Francisco Sole, Rui Chen, Hagop Kantarjian, Guillermo Garcia-Manero
Affiliations
Clinical Trial

Acquisition of cytogenetic abnormalities in patients with IPSS defined lower-risk myelodysplastic syndrome is associated with poor prognosis and transformation to acute myelogenous leukemia

Elias Jabbour et al. Am J Hematol. 2013 Oct.

Abstract

We hypothesized that the dynamic acquisition of cytogenetic abnormalities (ACA) during the follow up of myelodysplastic syndromes (MDS) could be associated with poor prognosis. We conducted a retrospective analysis of 365 patients with IPSS low or intermediate-1 risk MDS who had at least two consecutive cytogenetic analyses during the follow up. Acquisition of cytogenetic abnormalities was detected in 107 patients (29%). The most frequent alteration involved chromosome 7 in 21% of ACA cases. Median transformation-free and overall survival for patients with and without ACA were 13 vs. 52 months (P = 0.01) and 17 vs. 62 months (P = 0.01), respectively. By fitting ACA as a time-dependent covariate, multivariate Cox regression analysis showed that patients with ACA had increased risk of transformation (HR = 1.40; P = 0.03) or death (HR = 1.45; P = 0.02). Notably, female patients with therapy-related MDS (t-MDS) had an increased risk of developing ACA (OR = 5.26; P < 0.0001), although subgroup analysis showed that prognostic impact of ACA was not evident in t-MDS. In conclusion, ACA occurs in close to one third of patients with IPSS defined lower risk MDS, more common among patients with t-MDS, but has a significant prognostic impact on de novo MDS.

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Conflict of interest statement

Conflicts of interest: None of the authors have any conflict of interest.

Figures

Figure 1
Figure 1
Figure 1A. Pattern of ACA in patients with diploid karyotype. This chart represents CA acquired in patients with baseline diploid karyotype. Figure 1B. Pattern of ACA in patients with abnormal karyotype. The left chart represents CA acquired in patients with abnormal baseline karyotype. The right chart represents the new abnormalities acquired replacing the baseline clone.
Figure 1
Figure 1
Figure 1A. Pattern of ACA in patients with diploid karyotype. This chart represents CA acquired in patients with baseline diploid karyotype. Figure 1B. Pattern of ACA in patients with abnormal karyotype. The left chart represents CA acquired in patients with abnormal baseline karyotype. The right chart represents the new abnormalities acquired replacing the baseline clone.
Figure 2
Figure 2
Figure 2A. Transformation-free survival by ACA status (time-dependent covariate) Figure 2B. Overall survival by ACA status (time-dependent covariate)
Figure 2
Figure 2
Figure 2A. Transformation-free survival by ACA status (time-dependent covariate) Figure 2B. Overall survival by ACA status (time-dependent covariate)
Figure 3
Figure 3. A model of ACA in MDS
At baseline patients with lower risk MDS can be diploid (A) or have additional cytogenetic alterations (B). In a third of patients, additional/s cytogenetic clones (ACA or acquisition of cytogenetic alterations) are detected by conventional cytogenetic analysis. This phenomenon, in general, precedes development of acute myelogenous leukemia (AML) by a median time of 7 months. Molecular drivers of ACA are likely to be important determinants of AML transformation. The identification of patients at higher risk of ACA development may require closer follow up and more frequent cytogenetic analysis. Once patients develop ACA they should be considered for therapeutic intervention.
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