Evaluation of Conventional Cytogenetics Versus Fluorescence in Situ Hybridization Analysis in the Prognostic Scoring of Patients with Myelodysplastic Syndromes.

The myelodysplastic syndromes (MDS) encompass a heterogeneous group of progressive bone marrow insufficiency disorders characterized by chronic cytopenias and a risk of progression to acute leukemias. Non-random clonal chromosomal abnormalities, seen in almost 50% of patients with MDS, are associated with clinically and biologically distinct forms of the disease with prognostic and therapeutic implications. Currently, conventional cytogenetics (CC) and fluorescence in situ hybridization (FISH) techniques are commonly used to detect the chromosomal abnormalities in MDS. In this retrospective study, an effort is made to evaluate the merit of concomitant CC and FISH analyses for prognostic scoring in MDS.

A cohort of 86 MDS patients with both CC and FISH results were analyzed. The FISH technique focused on chromosomes 5, 7, 8 and 20. Data was collected on patient age, sex, WHO (World Health Organization) classification, CC and FISH findings, histologic transformation and transfusion dependence. For each patient, IPSS scores were calculated based on either CC (IPSS-CC) or FISH (IPSS-FISH). A weighted kappa statistic was calculated to measure agreement between the CC and FISH methods. Fisher's Exact tests were performed to measure the association between concordance/discordance in scores while survival time for concordant and discordant scores was calculated using Kaplan-Meier estimation and compared using a log-rank test. A significance test of 0.05 was assumed for all comparisons.

A cohort of 86 MDS patients with 64% male and median age of 68.5 years at diagnosis was studied. According to the WHO classification, 34% of the patients had refractory anemia (RA), 11% had refractory anemia with ringed sideroblasts (RARS), 13% had refractory anemia with excess blasts –1 (RAEB-1), 20% had refractory anemia with excess blasts –2 (RAEB-2) and 20% had refractory cytopenia with multilineage dysplasia (RCMD).

Of the 86 patients, 74 had concordant IPSS-CC and IPSS-FISH scores. The p-value for weighted kappa statistic was 0.87 with 95% confidence interval (0.80, 0.94) indicating that there is strong agreement beyond chance between the IPSS-CC and IPSS-FISH. Of the remaining 12 patients with discordant scores, 9 had IPSS-CC > IPSS-FISH while 3 patients (eliminated from comparative analysis for small size) had IPSS-FISH > IPSS-CC. Of the several variables compared between the concordant and discordant groups, only WHO subgroup turned out to be statistically significant. Concordant scores were significantly more likely to be in the RA (37%) and RCMD (23%) cohort, while all discordant patients were in the RAEB-1 (43%), RAEB-2 (29%), and RARS (14%) subgroups (p=0.004).

The 9 discordant patients were compared to 27 patients with concordant scores belonging to WHO subgroups RAEB-1, RAEB-2 and RARS. The prognostic variables for comparison were patient survival, leukemic transformation and transfusion dependence. 33% of the discordant patients had leukemic transformation as compared to 11% of concordant patients (p=0.15). Although the difference was large, the sample size was too small to be statistically significant.

Currently CC and FISH analyses are both being employed to detect the chromosomal abnormalities in MDS patients. This retrospective study indicates that there is statistically significant concordance between cytogenetic and FISH analyses. Conceivably, doing one or other test would most likely be sufficient for prognostic scoring of the vast majority of MDS patients especially those in RA and RCMD subclasses. The discordant scores are significantly more likely to occur in the RAEB-1, RAEB-2 and RARS classes hence justifying this subgroup of patients as potential candidates for both CC and FISH analyses. In our 9 patients with discordant scores (IPSS-CC > IPSS-FISH), a trend was observed towards higher leukemic transformation when compared to WHO subgroup matched concordant patients. While further validation of the current findings by larger prospective studies is awaited, this study unravels the MDS patient sub-population where CC and FISH could be complementary and not superfluous.

No relevant conflicts of interest to declare.