Prognositc Factors and Survival in Patients with Hypocellular Myelodysplastic Syndrome: Development of a Disease Specific Prognostic Score.

Myelodysplastic syndrome (MDS) is a heterogeneous group of bone marrow disorders characterized by dysplastic changes in the myeloid lineages, ineffective hematopoiesis, and an increased risk of transformation to acute myeloid leukemia (AML). In most cases, bone marrow is hyperceulluar but in 10 to 20% of cases, bone marrow can be hypocellular (defined as < 30% cellularity in patients < 70 years, or < 20% cellularity in patients 70 years or older), a condition that overlaps and is difficult to differentiate from aplastic anemia (AA). Currently, there are no good prognostic model for patients with hypocellular MDS.

In order to improve the prognostic assessment and to better understand the natural history of hypoplastic MDS, we analyzed the associations between disease characteristics and survival in 253 cases of hypocellular MDS presented to MDACC between 1993 and 2007. This is the largest study so far on patients with hypocellular MDS. We also compared the presenting characteristic and survival between these patients and a group of patients with hyper/normocelluar MDS (n=1725) during the same time period.

Patients with hypocellular MDS usually presented with more significant thrombocytopenia (p< 0.019), neutropenia (p< 0.001), low β-2 microglobulin (p< 0.001), more transfusion dependency (p< 0.001), and more intermediate-2/high risk disease (57% vs. 42%, p= 0.02) compared to their hyper/normocelluar counterparts. There was no difference in overall survival between the hypocellular and the hyper/normocellular groups (p= 0.312). We divided the patients randomly into study and test group, and a multivariate analysis of prognostic factor identified the following adverse, independent factors (p < 0.001): poor performance status (ECOG 2-4), poor bone marrow cytogenetics (chromosome 7 or complex), anemia (< 10 g/dl), increased bone marrow blasts (≥ 5%) and high serum LDH (> 600 IU/l). In this model, each characteristic has a score of 1. A new prognostic model based on these factors could classify this group of patients into three risk categories independent of IPSS score. Patients with low risk (n= 66; scores 0-1) had a median survival of 30 months, and 2-year/3-year survival of 62%/44%. Patients with intermediate risk (n=44; score 2) had a median survival of 19.4 months, and 2-year/3-year survival of 43%/20%. Patients with high risk disease (n= 59; scores 3-5) had a median survival of 7.3 months, and 2-year/3-year survival of 12%/6%. When this new prognostic model was applied to test group (n=84), the median survival was 55.7, 13.5 and 8.6 months (p< 0.0001) for patients in low, intermediate and high risk groups, respectively. Patients that received immunotherapy (ATG/cyclosporine) had a better median survival and overall survival than patients treated with supportive care, hypomethylating agents, or induction chemotherapy (p< 0.0001).

Here, we proposed a new simple prognostic model that allows to predict prognosis in patients with hypocellular MDS. Analysis of prognostic factors in patients with hypocellular MDS may help us understand the biology of the disease, and develop risk-adapted therapies for this group of patients.

No relevant conflicts of interest to declare.