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N. van Leeuwen-Kerkhoff et al.
group of patients as well (Figure 4B). A difference in leukemia-free survival did not reach statistical signifi- cance, probably because of the small numbers of patients (Figure 4C). To test whether TM as a single marker has an independent prognostic value in overall and leukemia-free survival a multivariate Cox regression analysis with back- ward stepwise elimination was performed. Covariates that were included in this analysis were hemoglobin level, absolute neutrophil count, platelet count, bone marrow
A
blast percentage, cytogenetic risk group and percentage of TM expression on monocytes. Information on all vari- ables was available for 60 patients (not shown). Covariates with a P value >0.10 were removed. Both the cytogenetic risk group as well as the percentage of TM expression were predictive markers for overall survival (P=0.001 and P=0.064, respectively). For leukemia-free survival, the percentage of blasts and TM expression had predictive value (P=0.010 and P=0.077, respectively).
B
C
Figure 4. Overall and leukemia-free survival is related to the presence of thrombomodulin-positive monocytes. As a cut-off percentage for the presence of throm- bomodulin (TM) on myelodysplastic syndrome (MDS) monocytes, the expression rate in the healthy donor cohort was used. The mean percentage + two standard deviations was calculated, resulting in a cut-off of 25.53%. Statistical differences were calculated using the log-rank test. (A) Overall survival data for 122 MDS patients and leukemia-free survival (LFS) data for 102 patients. A significant difference in overall survival was found between MDS patients with or without TM on BM monocytes (P=0.006). The median overall survival for patients with TM+ monocytes was 58 months while that for patients without TM was 30 months. The time to development of leukemia was significantly longer for patients with TM expression than for patients without TM expression (P=0.029). (B) Patients were further selected based on their low-risk status. Survival curves are shown for low-risk patients (according to the International Prognostic Scoring System and its revision) with or without TM+ monocytes. (C) LFS of low-risk patients in the TM+ and TM- groups. IPSS: International Prognostic Scoring System; IPSS-R: Revised International Prognostic Scoring System.
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