Transfusion intensity, not the cumulative red blood cell transfusion burden, determines the prognosis of patients with myelodysplastic syndrome on chronic transfusion support.

Transfusion-dependency is associated with poor prognosis in patients with MDS although the causal link for such association is disputed. This study tests thee hypotheses on the association between transfusion burden and prognosis in the MDS: (1) the cumulative transfusion burden is a confounder merely reflecting the time elapsed from diagnosis; (2) it is a surrogate for higher transfusion intensity, which would reflect a more severe disease; and (3) it is the total amount of transfused RBC units that influences on prognosis. We studied 191 transfusion-dependent patients with MDS or chronic myelomonocytic leukemia. Transfusion intensity was calculated at the time of each transfusion as the yearly-equivalent number of RBC units. The main outcome was acute leukemia-free survival from first transfusion. Median transfusion burden was 30 (range: 4-330) RBC units and 112 patients received ≥ 25 units after a median of 9 months from first transfusion. In nested Cox models, having received ≥ 25 RBC units had a significant effect on survival (P < 0.001) that was not abrogated by including follow-up ≥ 9 months as a time-dependent covariate. Including transfusion intensity in the model had a significant effect on leukemia-free survival (P < 0.001) and cancelled the prognostic value of having received ≥ 25 RBC units. In conclusion, transfusion intensity, instead of the cumulative transfusion burden, is the transfusion-related variable really influencing on the prognosis of patients with transfusion-dependent MDS.

Do we need to do fluorescence in situ hybridization analysis in myelodysplastic syndromes as often as we do?

Although conventional cytogenetics is considered the gold standard to detect chromosomal abnormalities in myelodysplastic syndromes (MDS), fluorescence in situ hybridization (FISH) is being increasingly used additionally. However, the real contribution of FISH analysis in the cytogenetic diagnosis of MDS has not been well defined. The aim of this study was to evaluate whether FISH studies are able to reveal chromosomal abnormalities in MDS patients undetected by conventional cytogenetics. One hundred seventy-four FISH studies were performed on bone marrow samples of 60 patients with MDS. The number of FISH studies in each patient was variable (1-5). FISH studies confirmed the G-banding cytogenetic findings in 99.4% (153/154) of samples and detected cytogenetic abnormalities in 25% (5/20) of cases in which the conventional cytognetic study failed. These results indicate that FISH studies provide relevant information in MSD in which the conventional cytogenetic analysis was unsuccessful but add little value to a normal katyotype in conventional cytogenetic analysis.

Hematopoiesis-related microRNA expression in myelodysplastic syndromes.

MicroRNAs (miRNAs) are negative regulators of expression of genes involved in hematopoiesis. The present study sought to link hematopoiesis-relevant miRNAs with myelodysplastic syndromes (MDS) and MDS progression to acute myeloid leukemia (AML). We assessed 25 mature miRNAs in total RNA from bone marrow (BM) and peripheral blood (PB) of 25 newly diagnosed patients with MDS and 12 controls. Twelve miRNAs in BM and six in PB were differentially expressed between patients with MDS and controls. Three of these miRNAs, belonging to the cluster 17-92, were overexpressed in both BM and PB. miR-15a in BM ( p = 0.034) and miR-16 in PB ( p = 0.005) were differentially expressed between low-risk and high-risk groups. miR-222 ( p = 0.0023) and miR-181a ( p = 0.014) expression was higher in AML than in MDS in both BM and PB. This study adds further evidence to the role of miRNAs in the pathogenesis of MDS and their transformation into AML.