The MDS genomics-prognosis symbiosis

Abstract

Myelodysplastic syndromes (MDS) are clonal disorders characterized by the accumulation of complex genomic abnormalities that define disease phenotype, prognosis, and the risk of transformation to acute myeloid leukemia. The clinical manifestations and overall outcomes of MDS are very heterogeneous with an overall survival that can be measured in years for some patients to a few months for others. Prognostic scoring systems are important staging tools that aid physicians in their treatment recommendations and decision-making and can help patients understand their disease trajectory and expectations. Several scoring systems have been developed in MDS with the International Prognostic Scoring System and its revised version, the most widely used systems in clinical practice and trial eligibility. These models and others use mainly clinical variables that are obtained from bone marrow biopsy and peripheral blood measurements. Adding molecular data to current models may improve its predictive power but the ultimate method to incorporate this information remains a work in progress. Novel methods to develop a personalized prediction model that provides outcomes that are specific for a patient are currently under way and may change how we think about risk stratification in MDS patients in the future.

Figure 1.

Prognostic factors in MDS. How the prognostic factors can be divided into disease-related and patient-related factors. EB, excess blast; FC, flow cytometry; MDS-MLD, MDS with multilineage dysplasia; MDS-SLD, MDS with single lineage dysplasia; PS, performance status; RS, ring sideroblast; U, unclassifiable. Adapted from Nazha et al with permission.

Figure 2.

Established prognostic models in MDS. The clinical characteristics and their cutoffs for each prognostic model in MDS. The cytogenetic groups for IPSS are: good: normal, −Y, 5q−, 20q−; poor: complex (≥3 abnormalities) or chromosome 7 abnormalities; and intermediate: other karyotypic abnormalities. The cytogenetic groups for IPSS-R are: very good: −Y, del(11q); good: normal, del(5q), del(12p), del(20q), double including del(5q); intermediate: del(7q), +8, +19, i(17q), any other single or double independent clones; poor: −7, inv(3)/t(3q)/del(3q), double including −7/del(7q), complex: 3 abnormalities; very poor: complex: >3 abnormalities. The cytogenetic group for LRPSS is diploid and 5q were favorable cytogenetics, all others were considered as unfavorable cytogenetics. The red blood cell (RBC) transfusion dependence is ≥1 RBC transfusion every 8 weeks over a period of 4 months. The WPSS was revised to include the degree of anemia (hemoglobin <9 g/dL in men and <8 g/dL in women). *The LRPSS is a model that only can be applied to MDS patients who belong to the IPSS low and intermediate-1 risk groups. 5q−, interstitial deletion of long arm of chromosome 5; ANC, absolute neutrophil count; BM, bone marrow; Hb, hemoglobin; LRPSS, lower-risk prognostic scoring system; plts, platelets; RA, refractory anemia; RAEB, refractory anemia with excess blasts; RARS, refractory anemia with ring sideroblasts; RCMD, refractory cytopenia with multilineage dysplasia; WBC, white blood cell count.

Figure 3.

Risk stratification, scores, and median OS by each model. Cat, category; Inter, intermediate; M, month; Y, year.

Figure 4.

Post-HMA failure model. The clinical characteristics of post-HMA failure model and the survival curves for each risk category.