Impact of transfusion dependency on survival in patients with early myelodysplastic syndrome without excess of blasts

Abstract 

We present a retrospective analysis of 137 patients with early MDS without excess of blasts that revealed transfusion dependency in 87% of the cases. A significant difference in overall survival was noted between patients receiving ≤2units and those receiving >2units of RBC transfusions/month (65.0 vs. 35.3 months, respectively, P=0.02). Univariate statistical analysis identified the presence of disease progression to advanced MDS (χ²=26.4, P=0.001) and the administration of >1 or >2units of RBC per month (χ²=15.9 and 14.6, respectively, P=0.001) as the most important parameters affecting survival. Nevertheless, even the administration of 1 RBC unit every 4–8 weeks had a significantly adverse impact on survival compared to non-transfused patients. Transfusion dependency itself did not affect disease progression as determined by the presence of multilineage dysplasia and adverse karyotype (expressed by the IM-1 or IM-2 score). Multivariate analysis confirmed disease progression towards leukemia as a highly significant independent variable affecting survival (P=0.0001). None of the other evaluated parameters had a significant impact on survival in patients with progressive disease. In non-transplanted patients without MDS progression, administration of >2units of RBC transfusions/month was the only independent variable with adverse impact on survival in patients with unilineage erythroid dysplasia (P=0.02). In patients with multilineage dysplasia, only heavy transfusion dependency (>3TURBC/month) and serum ferritin >2000μg/l adversely affected survival (P=0.03). Modification of the WPSS by replacing transfusion dependency with initial Hb level <80g/l retained its prognostic relevance and allowed the identification of a potential risk subset of early MDS patients with intermediate and high scores and limited survival (<40% at 5 years) as early as at the time of diagnosis. Our results confirm a significant negative impact of transfusion dependency on survival in patients with early MDS without excess of blasts. The main risk subgroup is characterized by unilineage dysplasia limited to erythropoiesis in combination with dependency on >2TU of RBC per month. These patients usually have prolonged survival that leads to the development of heavy transfusion iron overload and they thus represent the most important target group for intensive chelation therapy.

Abbreviations: AML, acute myeloid leukemia, EF, ejection fraction, FAB, French–American–British, IM, intermediate, IPSS, International Prognostic Scoring System, ISCN, International System for Cytogenetics Nomenclature, LFS, leukemia free survival, LV, left ventricular, LW, low, MDS, myelodysplastic syndrome, MRI, magnetic resonance imaging, OS, overall survival, PNH, paroxysmal nocturnal hemoglobinuria, RA, refractory anemia, RARS, refractory anemia with ringed sideroblasts, RBC, red blood cell, RCMD, refractory cytopenia with multilineage dysplasia, RCMD-RS, refractory cytopenia with multilineage dysplasia with ringed sideroblasts, TU, transfusion unit, WHO, World Health Organization, WPSS, WHO classification-based Prognostic Scoring System

Keywords: Myelodysplasia, Transfusion, Iron overload, Survival, Prognosis, WPSS