Time-dependent changes in mortality and transformation risk in MDS

Abstract

• Hazards regarding mortality and leukemic transformation in MDS diminish over time in higher-risk but remain stable in lower-risk patients.• This change of hazard indicates time-dependent attenuation of power of basal risk scores, which is relevant for clinical decision making.In myelodysplastic syndromes (MDSs), the evolution of risk for disease progression or death has not been systematically investigated despite being crucial for correct interpretation of prognostic risk scores. In a multicenter retrospective study, we described changes in risk over time, the consequences for basal prognostic scores, and their potential clinical implications. Major MDS prognostic risk scoring systems and their constituent individual predictors were analyzed in 7212 primary untreated MDS patients from the International Working Group for Prognosis in MDS database. Changes in risk of mortality and of leukemic transformation over time from diagnosis were described. Hazards regarding mortality and acute myeloid leukemia transformation diminished over time from diagnosis in higher-risk MDS patients, whereas they remained stable in lower-risk patients. After approximately 3.5 years, hazards in the separate risk groups became similar and were essentially equivalent after 5 years. This fact led to loss of prognostic power of different scoring systems considered, which was more pronounced for survival. Inclusion of age resulted in increased initial prognostic power for survival and less attenuation in hazards. If needed for practicability in clinical management, the differing development of risks suggested a reasonable division into lower-and higher-risk MDS based on the IPSS-R at a cutoff of 3.5 points. Our data regarding time-dependent performance of prognostic scores reflect the disparate change of risks in MDS subpopulations. Lower-risk patients at diagnosis remain lower risk whereas initially high-risk patients demonstrate decreasing risk over time. This change of risk should be considered in clinical decision making. (Blood. 2016;128(7):902-910)

A Population-Based Study on Myelodysplastic Syndromes in the Lazio Region (Italy), Medical Miscoding and 11-Year Mortality Follow-Up: The Gruppo Romano-Laziale Mielodisplasie Experience of Retrospective Multicentric Registry

“…The Kaplan-Meier curve stratified by MDS subtype according to 2008 WHO classification (Figure 1B), is similar to other studies of the same type,28 with shorter survival for patients with RAEB I or RAEB II. Survival was similar in low-risk MDS (RCMD, RA, and RARS), and it reached a plateau in high-risk MDS (RAEB I and RAEB II), similar to other registries 1,6. Patients with a 5q- syndrome survived the longest, followed by MDS-U patients, although numbers are low (24 and 23 patients, respectively).…”

“…However, in individuals aged over 70 years, the incidence constantly increases up to 40–60 /100,000 2,3. Survival of MDS patients is poor,4 with 2–4 years reported median overall survival (OS) 1,5,6. Factors known to impact survival include age, the number of blasts, cytogenetic profile, cytopenias, transfusion requirements and disease type, according to 2008 WHO classification 7.…”

Risk and timing of cardiovascular death among patients with myelodysplastic syndromes

“…A recent analysis of 7212 primarily untreated MDS patients found that revised International Prognostic Scoring System risk groups equilibrated after 3.5 years, such that the hazard of death or transformation to leukemia was equivalent between groups. 27 We found that for those patients who were alive 5 years after their diagnosis, the cumulative risk of death attributed to CVD was similar to that of death from an MDS or leukemia. In fact, for patients with lower-risk MDS who were alive at 5 years, we found that the risk of death attributed to CVD was equal to and trending toward being greater than the deaths attributed directly to MDS.…”

Age-related clonal hematopoiesis and monoclonal B-cell lymphocytosis/chronic lymphocytic leukemia: a new association?

“…CLL is always preceded by a high MBL count, 7 MM is almost always preceded by monoclonal gammopathy of undetermined significance (MGUS), 8 and at least a quarter of all patients with myelodysplastic syndromes (MDS) have disease that evolves into AML. 9 Deep genomic sequencing of normal subjects revealed that during human aging, the expansion of 1 or more hematopoietic stem and progenitor cells (HSPC) will result in clones that will sustainably contribute more than others to the production of mature blood cells. Accordingly, age-related clonal hematopoiesis (ARCH) is defined as the expansion of HSPC clones, harboring specific, disruptive, and recurrent genetic variants, in individuals without clear diagnosis of hematologic malignancies.…”