Clone Size By Conventional Cytogenetics in Myelodysplastic Syndromes Correlates with Clinical Features and Outcomes

Abstract

Introduction Chromosomal abnormalities are detected in 30-40% of myelodysplastic syndromes (MDS) patients (pts) using conventional karyotyping of 20 metaphases. Conventional cytogenetics remain crucial for risk stratification and certain cytogenetic abnormalities are MDS defining. The Revised international prognostic scoring system (IPSS-R) and its new molecular version (IPSS-M) account for conventional cytogenetic abnormalities regardless of the number of metaphases those abnormalities are detected among (dichotomous assignment). We aimed to assess correlation of "clone size by conventional cytogenetics” defined as percentage of metaphases where chromosome abnormalities are detected with certain clinical features and outcomes in MDS. Methods We retrieved cases from Moffitt MDS database with cytogenetics of interest (i.e. del5q, del20q, del7q/-7, chromosome 3 (ch3), trisomy 8 (+8) and complex karyotype). Inclusion for this study required presence of at least 10 metaphase analysis of chromosome abnormalities by conventional cytogenetics at time of diagnosis or prior to any therapy. We assessed clinical features of interest and outcomes based on % of cells/metaphases harboring the chromosome abnormality using G-banding "conventional cytogenetics clone size". Results This study included 1096 pts, 151 with isolated del5q, 134 pts with del20q, 113 pts with del7q/-7, 38 pts with isolated ch3, 163 pts with +8, and 497 pts had complex karyotype. Detailed disease baseline characteristics, molecular/cytogenetic data, risk stratification and outcomes of all those cohorts were available and reviewed. Among 151 isolated del 5q, pts with >75% metaphases harboring del5q had more severe anemia (hgb < 8.0 g/dl), 29% compared to 10%,12%, and 18% for pts with <25%, 25-50, and 51-75% metaphases, respectively (p .03). Among pts who were treated with lenalidomide (n=98), there was a trend for higher response rate among pts with >75% del5q metaphases (61% vs 46%; p=.09). There was no difference in presence of TP53-m based on % of metaphases harboring del5q. We identified 134 pts with del20q, pts with >75% del20q metaphases had more thrombocytopenia (< 100 u/l), 65% compared to 42%, 26%, and 42% for pts with <25%, 25-50, and 51-75% metaphases, respectively (p .005). For 163 pts with +8, the median OS was 59 months (mo) for pts with <25% +8 detected metaphases compared to 36 mo for those >25%. (p=.05) For 113 pts with del7q/-7, the median OS was worse for -7 (n= 81) compared to del7q (n=32); (18.5 vs 29 mo, p =.024). The median OS was 98 mo for del7q/-7 with <25% metaphases compared to 18 mo for those > 25% metaphases, p=.009. There was no difference in response to hypomethylating agents based on 25% cutoff. We had 38 pts with isolated ch3 abnormality, the median OS was 122 mo for 2 pts with <25% metaphases compared to 24 mo for those >25%, p=.09. Finally, among 497 pts with complex karyotype, the median OS was 20 mo for those with <25% metaphases compared to 12 mo for >25% (p=.01). There was no difference in presence of TP53-m based on % of metaphases. Conclusions The number of cells harboring chromosome abnormalities in MDS using regular karyotyping "clone size by conventional cytogenetics” strongly correlated with clinical features and outcomes. A 25% cut off should be examined in context of IPSS-R and IPSS-M scoring for cytogenetic risk rather than dichotomous assignment to risk group. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal