The impact of clonal size on the revised international prognostic scoring system (R-IPSS) in myelodysplastic syndromes (MDS) with a single cytogenetic abnormality.

Abstract

7068 Background: Cytogenetics is the backbone of the R-IPSS for MDS, contributing the most points (0 to 4) to the total scoring system. The current R-IPSS cytogenetics does not factor in the clone size or the number of abnormal metaphases. The International System for Human Cytogenetic Nomenclature (ISCN) in 2016 defined the clone by the presence of a structural rearrangement in at least 2 metaphases or 3 metaphases in case of monosomies. Methods: This is a retrospective study from the Mayo Clinic records for patients with confirmed MDS by a hematopathology review. Analysis included patients with adequate karyotyping of 20 metaphases only. Patients were divided into 3 groups (grp) based on their R-IPSS cytogenetics category (Intermediate, Poor and Very Poor). Patients with a single abnormal clone only were included. The size of the abnormal clone was calculated by dividing the number of abnormal metaphases by 20. The overall survival (OS) of each R-IPSS grp with different clonal percentage was compared to the diploid cytogenetics (DC) group. The Good and Very good R-IPSS cytogenetics were excluded. Survival estimates were calculated by Kaplan-Meier curves and log-rank testing using JMP v.13. Results: Of 1301 patients, 36.5% (n = 475) had a DC, 49% (n = 637) had an abnormal karyotype and 15% (n = 189) had no available cytogenetic results. Of those with abnormal karyotype, 58% (n = 372) had a single clone. Of those with a single clone, 70% (n = 260) had a single chromosomal abnormality. The OS of the 3 groups was statistically different and consistent with their R-IPSS score. OS was higher in the DC group (OS = 54 months, n = 474) compared to the Intermediate (OS = 30.5 months, n = 121), Poor (OS = 21.1 months, n = 49), and Very poor (OS = 8.7 months, n = 75), p < 0.005 for all grps. The clone size had no impact on overall survival above 5% when combining the 3 grps, the lowest threshold to make statistical conclusions was 10% (p = 0.01). Conclusions: The clonal percentage of any abnormality detected by conventional karyotype did not affect OS in patients with MDS that have an R-IPSS risk of intermediate or above. Therefore, any chromosomal abnormality should be included in the R-IPSS cytogenetics.