Unknown Risk Should be Considered High-Risk in Myelodysplastic Neoplasms: A Multicenter Study in 219 Patients in Colombia

Background

Myelodysplastic neoplasms (MDS) are a heterogeneous clonal disorder of hematopoietic stem cells characterized by dysplasia, ineffective hematopoiesis, peripheral cytopenias, risk of progression to acute myeloid leukemia (AML), and poor survival in high-risk patients. Prognosis is determined by knowledge of cytogenetic and molecular data. Specific genetic abnormalities, such as deletion of the long arm of chromosome 5 (del(5q)), TP53 inactivation, and SF3B1 mutation, are increasingly associated with disease prognosis and therapeutic determinants. Treatment of lower-risk MDS is primarily symptomatic to improve cytopenias. Higher-risk disease warrant disease-directed therapy, with allogeneic transplantation being the only curative strategy. In low- and middle-income countries, access to cytogenetic evaluation tests is limited, which makes adequate therapeutic management difficult. In this work, we demonstrate that patients with unknown risk behave in terms of survival as high-risk patients.

Methods

An observational, cross-sectional, multicenter study was conducted. The demographic and clinical characteristics, risk of leukemic transformation, and overall survival of patients with MDS were analyzed based on the IPSS R score, considering the unknown risk in the analyses. The ethics committee of the participating institutions approved this work.

Results

Two hundred nineteen patients with MDS were included, over 18 years of age; 51.6% were women (n=113), and the majority were of primary etiology (95.9%). The median age at diagnosis was 74 years (20-92 years). According to the WHO 2016 classification, the most frequent subtypes were unilineage dysplasia in 30.6% and multilineage dysplasia in 27.9%. The number of cytopenias at diagnosis was 2 in 40.6%, and the most frequent was anemia in 84.5%. Cytogenetic studies were performed in only 50%, and molecular studies in only 3.7%. Karyotype abnormalities were found in 7.8%; the most frequent abnormality was 5q deletion in 2.3%, followed by complex karyotype in 1.4%. The disease risk established by IPSS-R was very high at 2.7%, high at 5.5%, intermediate at 12.3%, low at 21.5% and very low at 7.8%. The risk status was indeterminate in 50%. High risk was defined as patients with intermediate, high, and very high IPSS-R; low risk was defined as patients with low and very low risk IPSS-R.

The proportion of patients with transformation to acute myeloid leukemia was 12.8% (n=28), the median time from diagnosis to transformation was 9.7 months (0.5-114), which was most frequent in the high-risk IPSS-R group at 39.28%, followed by unknown risk at 17.02% and finally low risk at 1.45%.

The median overall survival of the entire cohort was 24 months (95% CI 16.44-31.533). Survival in patients with low-risk IPSS-R was 53 months (95% CI 28.22-77.79), and in high-risk IPSS-R was 17 months (95% CI 6.80-27.19). Strikingly, in the unknown risk group, the median overall survival was 17 months (95% CI 10.60-23.39), similar to that observed in patients with high-risk IPSS-R.

Discussion

In low- and middle-income countries, access to cytogenetic and molecular testing for the diagnosis and prognosis of MDS is limited, resulting in disease risk staging often being incomplete. In these patients with indeterminate risk, survival behaviour and transformation to acute myeloid leukemia are similar to those observed in the IPSS-R high-risk group. These findings emphasize the importance of comprehensive risk assessment in MDS.

No relevant conflicts of interest to declare.