PROGRESSION SCORE FOR ACUTE LEUKEMIA - A NEW PROGNOSTIC SCORE IN MDS?
(Abstract release date: 05/18/17)
EHA Library. Cortesão E. 05/18/17; 182628; PB1914
Emília Cortesão
Contributions
Contributions
Abstract
Abstract: PB1914
Type: Publication Only
Background
Since 1997, the International Prognostic Scoring System (IPSS) has been the standard for stratifying patients with Myelodysplastic Syndrome (MDS). Although other models were proposed to improve this stratification, some issues remain, notably the identification of low-risk patients with poor prognosis who may benefit from earlier and/or aggressive therapy.
Aims
The aim of our work was the conception of a new prognostic score in MDS, based in the cellular and molecular disease characterization.
Methods
Our sample consisted of 102 patients diagnosed with MDS de novo. The median age was 74 years (22-89), with a 0.8 Male to Female ratio. The subtypes, according to the World Health Organization 2008, were Refractory Cytopenia with Multilineage Dysplasia (RCMD) (n=52), Refractory Cytopenia with Unilineage Dysplasia (RCUD) (n=12), Refractory Anemia with Excess Blasts type 1(RAEB-1) (n=8), RAEB-2 (n=8), Refractory Anemia with Ringed Sideroblasts (n=6), 5q- syndrome (n=4) and Chronic Myelomonocytic Leukemia (n=12). The IPSS based stratification was: low (n=37), intermediate-1 (n=39), intermediate-2 (n=10) and high (n=1). Several variables were analyzed: hematological (leukocytes, neutrophils, hemoglobin, platelets, blasts and ring sideroblasts), biochemical (erythropoietin, β2-microglobulin, folic acid, vitamin B12, ferritin, LDH), imunophenotypic (hematopoietic stem cell characterization by flow cytometry, FC, using the markers, CD34 / CD117 / CD123 / GlicoP / IL-6 / TNFa) and molecular characteristics (methylation profile of genes p15, p16, DAPK, R1, R2, R3 and R4 performed by PCR-MS, and evaluation of expression levels of regulatory molecules of apoptosis BCL-2, BAX, TRAIL, R1, R2, R3, R4, FAS, Survivin, Caspase 3, Cit C, GlycoP and p53, by FC).
Results
In the 60-month follow-up, 11 patients progressed to Acute Myeloblastic Leukemia (AML), 7 with RAEB-2, 2 with RCMD, 1 patient with RAEB-1 and another with CMML. These patients had a higher % of ring sideroblasts and blasts; higher scores on IPSS, IPSS-R and WPSS; lower platelet counts, higher erythropoietin levels and greater expression of CD34 / CD117 / IL-6. Assigning a value (+1) to each altered variable a new prognostic score was obtained, which we named Progression Score for Acute Leukemia. We observed that patients belonging to subtypes with the highest scores were those that progressed to AML, namely RAEB-1, RAEB-2 and RCMD.
Conclusion
In conclusion, we believe that this score may contribute to evaluate the risk of progression to AML, by reflecting the heterogeneity of MDS and its multifactorial etiology. The coexistence of many altered variables not only contributes to the etiopathogenesis of MDS but also allows the assessment of potential leukemic transformation.
Session topic: 9. Myelodysplastic syndromes - Biology
Keyword(s): Progression, prognosis, Molecular markers, MDS
Abstract: PB1914
Type: Publication Only
Background
Since 1997, the International Prognostic Scoring System (IPSS) has been the standard for stratifying patients with Myelodysplastic Syndrome (MDS). Although other models were proposed to improve this stratification, some issues remain, notably the identification of low-risk patients with poor prognosis who may benefit from earlier and/or aggressive therapy.
Aims
The aim of our work was the conception of a new prognostic score in MDS, based in the cellular and molecular disease characterization.
Methods
Our sample consisted of 102 patients diagnosed with MDS de novo. The median age was 74 years (22-89), with a 0.8 Male to Female ratio. The subtypes, according to the World Health Organization 2008, were Refractory Cytopenia with Multilineage Dysplasia (RCMD) (n=52), Refractory Cytopenia with Unilineage Dysplasia (RCUD) (n=12), Refractory Anemia with Excess Blasts type 1(RAEB-1) (n=8), RAEB-2 (n=8), Refractory Anemia with Ringed Sideroblasts (n=6), 5q- syndrome (n=4) and Chronic Myelomonocytic Leukemia (n=12). The IPSS based stratification was: low (n=37), intermediate-1 (n=39), intermediate-2 (n=10) and high (n=1). Several variables were analyzed: hematological (leukocytes, neutrophils, hemoglobin, platelets, blasts and ring sideroblasts), biochemical (erythropoietin, β2-microglobulin, folic acid, vitamin B12, ferritin, LDH), imunophenotypic (hematopoietic stem cell characterization by flow cytometry, FC, using the markers, CD34 / CD117 / CD123 / GlicoP / IL-6 / TNFa) and molecular characteristics (methylation profile of genes p15, p16, DAPK, R1, R2, R3 and R4 performed by PCR-MS, and evaluation of expression levels of regulatory molecules of apoptosis BCL-2, BAX, TRAIL, R1, R2, R3, R4, FAS, Survivin, Caspase 3, Cit C, GlycoP and p53, by FC).
Results
In the 60-month follow-up, 11 patients progressed to Acute Myeloblastic Leukemia (AML), 7 with RAEB-2, 2 with RCMD, 1 patient with RAEB-1 and another with CMML. These patients had a higher % of ring sideroblasts and blasts; higher scores on IPSS, IPSS-R and WPSS; lower platelet counts, higher erythropoietin levels and greater expression of CD34 / CD117 / IL-6. Assigning a value (+1) to each altered variable a new prognostic score was obtained, which we named Progression Score for Acute Leukemia. We observed that patients belonging to subtypes with the highest scores were those that progressed to AML, namely RAEB-1, RAEB-2 and RCMD.
Conclusion
In conclusion, we believe that this score may contribute to evaluate the risk of progression to AML, by reflecting the heterogeneity of MDS and its multifactorial etiology. The coexistence of many altered variables not only contributes to the etiopathogenesis of MDS but also allows the assessment of potential leukemic transformation.
Session topic: 9. Myelodysplastic syndromes - Biology
Keyword(s): Progression, prognosis, Molecular markers, MDS
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