| dc.description.abstracteng | Myelodysplatic syndrome are defined as a group of heterogeneous, clonal hematopoietic diseases characterised by ineffective haematopoiesis, with an increased risk to undergo transformation into acute myelogenous leukaemia. The genetic instability of the malignant clone can lead to subsequent cytogenetic evolution.
The goal of this study was to compare and describe the cytogenetic and clinical course of the disease in elderly patients with advanced MDS who were either treated with 5 – azacytidine or underwent allogeneic hematopoietic stem cell transplantation following 5 – azacytidine. In addition the prognostic value of cytogenetic courses was examined.
50 patients with advanced MDS were enrolled in the study : “Comporasion between 5-azacytidine treatment and 5 – azacytidine followed by allogeneic hematopoietic stem cell transplantation in elderly patients with advanced MDS according donor avaliability.” Patients were randomised after 4 courses of 5 – azacytidine according to donor availability into two groups: Group A included patients without a HLA – compatible donor (10/10 alleles) with stable disease or who responded well to treatment. Group A continued their treatment with 5 – azacytidine. Patients with a HLA – compatible donor were randomised into group B. They received four courses of 5 – azacytidine before undergoing allogeneic hematopoietic stem cell transplantation. Data was collected on initial point of diagnosis and during further evaluation of the course of disease. Cytogenetic evaluation and data collection took place at initial diagnosis, after four courses of 5 – azacytidine treatment and in group A after eight completed courses of 5 – azacytidine and in group B at d+100 after completing allogeneic hematopoietic stem cell transplantation.
A collective of 50 patients were included in the study and their data analysed: with 15 patients being randomised into group A and 32 patients being randomised into group B. Three patients could not be distributed into one of the respective groups due to progressive course of disease. For statistical stratification three cytogenetic groups were established: complex, not – complex and normal.
There was no statistically significant difference in survival rate between the three cytogenetic groups (p=0.24).
After four courses of 5 – azacytidine treatment thrombocyte – and haemoglobin count were significantly increased from the point of initial diagnosis (p=0,007, p=0,004). The percentage of blast cells in the bone morrow was significantly reduced (p=0,001).
After eight courses of 5 – azacytidine treatment thrombocyte – and haemoglobin count were significantly increased from the point of initial diagnosis (p=0,007, p=0,032). The percentage of blast cells in the bone morrow was significantly reduced (p=0,024).
After four courses of 5 – azacytidine the distribution of cytogenetic groups was improved (p=0,027) and the clone seize decreased significantly compared with the initial results (p=0,023).
A response to 5 – azacytidine treatment could already be shown after four courses, even though haematological response was observed earlier in the course of treatment than cytogenetic response.
After allogeneic hematopoietic stem cell transplantation the haemoglobin - , neutrophil – and thrombocyte count was much higher (p=0,07, p=0,012, p<0,01) and the percentage of blasts in the bone marrow much lower than at initial diagnosis (p<0,01).
In comparison patients of group B achieved much better results. Leukocyte – and neutrophil count was significantly higher (p=0,02, p=0,005) and percentage of blasts in the bone marrow was significantly lower (p=0,05, p=0,004). The transfusion requirement of erythrocytes and thrombocytes were significantly lower (p=0,001, p<0,01).
The clonal seize was significantly reduced after allogeneic hematopoietic stem cell transplantation in comparison with 5 – azacytidine treatment (p=0.03). Survival rate was significantly longer in patients with allogeneic hematopoietic stem cell transplantation (104 d vs 760 d). No significant statistical difference could be shown between mean overall survival rates in patients with or without decrease of clonal seize (p=0.49).
Earlier studies showed that patients with MDS and cytogenetic evolution had a poor prognosis and a higher chance to develop acute myelogenous leukaemia. Those patients had not received treatment for MDS. This study examined the course of disease under treatment and statistical evaluation showed that treatment with 5 – azacytidine and allogeneic hematopoietic stem cell transplantation can reduce the rate of malignant clones. Further research is needed to define which is the most effective treatment in patients with cytogenetic evolution. | de |