Cytogenetics As a Prognostic Factor Of The Overall Survival (OS) Of Mexican Patients With Myelodysplastic Syndrome (MDS)
Authors: Rodriguez-Gonzalez Maria Guadalupe , Martinez-Ibarra Yaneth , Vela-Ojeda Jorge , Nacho-Vargas Kevin , Meillon Luis , Fattel Yamile , Robledo Julio , Romero-Salas Tonatiuh , Xolotl-Castillo Moises 
Published: October 2019

Abstract

Introduction
MDS are a heterogeneous group of acquired clonal diseases, characterized by an increase of the apoptosis and several grades of cytopenias. They originate in hematopoietic stem cells with cytogenetic and molecular abnormalities, having the risk of evolving into an acute myeloid leukemia (AML).
There are no clinical data of the characteristics of the patients with MDS in Mexico, thus we consider necessary to know the behavior of this disease in our population, also to evaluate the cytogenetic alterations, and to investigate whether they are associated with the OS.

Methods
A longitudinal-observational study was performed at the MDS clinic of the Hematology Department of the Specialties Hospital of the Centro Médico Nacional La Raza of the Instituto Mexicano del Seguro Social (IMSS), from January 25, 2005 to January 25, 2013. The primary objective was to evaluate the epidemiological characteristics and the cytogenetic findings of the patients with MDS in our population, establishing its correlation with the OS. We included patients >16 y.o., male and female, with diagnosis of newly diagnosed MDSs with a cytogenetic testing available (GGT-band analysis performed at Quest Diagnostics and Genetica Pre y Post Natal). SPSS version 20 was used for statistical analysis. Survival was evaluated through KM curve. A Multivariate analysis with logistic regression was performed in order to know the OR and 95% CI and a p<0.05 was accepted as statistically significant.

Results
A total of 92 patients were included, 44 (47.8%) men, and 48 (52.2%) women. The cytogenetic study was normal in 72 (78.3%) of the patients and 20% (21.7%) had an abnormal cytogenetic study. The cytogenetic abnormalities were as follows: 5 (25%) had complex karyotype, 3 (15%) had –Y, 2 (10%) hypodiploidy, 2 (10%) del9, 1 (5%) del7, 1 (5%) +9, 1 (5%) t 1;5, 1 (5%) 17p-, 1 (5%) del21, 1 (5%) +19, 1(5%) del5q y 1(5%) +8.
77 patients (83.7%) had favorable cytogenetic risk; 8 (8.7%) intermediate cytogenetic risk; and 7 (7.6%) poor risk.
The IPSS risk stratification was: low risk in 33 (35.9%) of the patients, intermediate-1 risk in 39 (53.3%), intermediate 2 risk in 5 (5.4%), and high risk in 5 (5.4%).
The median OS was 85 months (figure 1), with a median follow-up of 35 months (2-96 months). The median survival for the favorable cytogenetic risk was 82.7 months 95% CI; 74.7-90.6), for the intermediate cytogenetic risk 73.6 months (95% CI; 49.06-98.1), and for the poor cytogenetic risk, 46.8 months (95% CI; 10.6-18.4). The patients with favorable cytogenetic risk had a better survival than those with intermediate or poor cytogenetic risk (P= .001 Log-rank test). (Figure 2)
Of the 92 patients, 10 (10.08%) progressed to acute myeloid leukemia the cytogenetic risk of these patients was as follows: 5 had a favorable risk karyotype and 5 had poor risk karyotype. The patients with favorable cytogenetic risk had a lower risk of progression in comparison with those with poor risk karyotype (P= 0.000). The median PFS to AML was 18.7 months (95 CI 4.1-33.2). Survival per cytogenetic risk group: for the favorable cytogenetic risk the median survival was 22.2 months 95% CI (.76-43), and for the poor cytogenetic risk it was 15.2 months, 95% CI (.0-36.8). (P= .362 Log-rank test). (Figure 3). The performance of the cytogenetic study to classify the patients and to estimate the IPSS is statistically associated with mortality (P 0.006). In the multivariate analysis was found that there is an association, independently of the cytogenetic study with favorable risk according to the IPSS, with the protection against mortality, with an OR=0.141, (95% CI 0.042-0.47). This confered a protection factor of 86% for the survival, independently of the treatment and the MDS type.

Conclusion
Cytogenetic alterations in MDS patients differs importantly from other reports, since only a 21.7% of our patients had an abnormal cytogenetic finding. Nevertheless cytogenetic evaluation was very important for this population since it confirmed its prognostic importance for the OS of the Mexican MDS patients.

Disclosures:
Nacho-Vargas: Novartis Oncologia Mexico: Employment. Romero-Salas:Novartis Oncologia Mexico: Employment.