Predictors of Outcome In Patients with Myelodysplastic Syndromes Living In Western Pennsylvania

The myelodysplastic syndromes (MDS) are a collection of hematologic disorders that affect older adults. The baseline characteristics and risk factors for evolution to acute myeloid leukemia (AML) and death in MDS have not been completely defined. To gain a better understanding of MDS disease progression, we analyzed data from a large unselected cohort of MDS patients from the University of Pittsburgh Medical Center Network Cancer Registry in Western Pennsylvania.

Demographic and baseline clinical data, including MDS subtype, treatment, cytogenetics, and cytopenias were derived from both patients' medical charts and electronic medical records. The MDS subtypes were recorded according to the French-American-British classification system (FAB). The IPSS score was calculated by one of the study investigators using the following criteria: bone marrow blasts were scored as 0 for values of <5%, as 0.5 for values of 5–10%, 1.5 for values of 11–20%, and as 2.0 for values of 21–30%. Good cytogenetic characteristics included normal karyotype, -Y, 5q-, and 20q-. Poor cytogenetics included chromosome 7 abnormalities and complex aberrations (>3 abnormalities). The intermediate risk group included all other aberrations. Four risk groups were formed based on the scores; Low, Int-1, Int-2, and High. Multivariable Cox proportional hazard models were developed to assess factors associated with AML evolution and survival. Covariates in these models included gender, race, diagnosis, age, smoking status, alcohol history, family history of cancer, previous cancer, blast percentage, blood parameters, therapies, MDS subtypes, and International Prognostic Scoring System score (IPSS). Differences in survival were tested using the Wilcoxon Log-Rank test.

Of 214 MDS patients included in this study, 129 were male (60%), the majority were Caucasian, 34% were diagnosed after the age of 70 years. More than half of the patients (63%) had a history of smoking, while 44% reported alcohol use and roughly half of the population (49%) reported a family history of cancer. Patients were followed for an average of 22 months after diagnosis. At baseline, the median hemoglobin level for all patients was 9.4 g/dL, and median neutrophil count was 1.45 × 10⁹/L, with no significant gender differences. The median platelet count was 88 × 10⁹/mm³ with 26.1% of the patients presenting with a platelet count < 50 × 10⁹/mm³. The median blast count was 4.3% blasts, and female patients had a non statistically significantly lower median count compared to their male counterparts. Overall, the 36-month survival rate was 19.0% (95% CI: 14.0 – 24.5%): 22.4% (95% CI: 16.4 – 29.0%) for lower-risk MDS patients and 5.0% (95% CI: 0.1 – 14.8%) for higher-risk MDS patients (p = 0.0007). During follow-up, 33% of patients developed AML. A family history of cancer (adjusted hazards rate (aHR) =2.4; 95% CI= 1.2 – 4.8) was a significant predictor of disease progression to AML, as was having 5% or more blasts at diagnosis (aHR=4.3; 95% CI=1.7 – 10.9), which was also a predictor for death (aHR=3.1; 95% CI=1.8 – 5.3). Factors associated with a borderline increase in risk of death include age >70 years at diagnosis (aHR = 1.3; 95% CI = 0.9 – 1.8) and previous diagnosis of cancer other than MDS (aHR = 1.3; 95% CI = 0.9 – 1.9). Increasing numbers of chemotherapy sessions (3 or more sessions versus 1: aHR – 0.5; 95% CI = 0.3 – 0.8) and a platelet count of >50×10³/mm³ (aHR = 0.8; 95% CI = 0.5 – 1.1) were inversely associated with death.

This is one of the first studies to present the contribution of both demographic and clinical factors to survival and AML development in a large population-based cohort of MDS patients.

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