CHARACTERIZATION OF THE ERYTHROPOIETIC RESPONSE OF THE DYSPLASTIC MARROW
(Abstract release date: 05/19/16)
EHA Library. Pereira M. 06/09/16; 134810; PB1910
Dr. Marta Pereira
Contributions
Contributions
Abstract
Abstract: PB1910
Type: Publication Only
Background
Myelodysplastic syndromes (MDS) are characterized by peripheral citopenias within the context of a dysplastic, and frequently hypercellular bone marrow.Anemia is one of the most frequent findings, with 20 to 40% of patients responding to exogenous erythropoietin (Epo), with or without the addition of G-CSF, despite normal to elevated levels of serum endogenous Epo, reflecting the complexity of erythropoietic control in these syndromes. Nevertheless, a different likelihood of response to exogenous Epo has been identified between patients with Normal (<=20 IU/L), Mildly Elevated (20-100 IU/L), Moderately Elevated (100-500 IU/L) and Markedly Elevated (>500 IU/L) endogenous Epo levels.
Aims
To further characterize the early erythropoietic response in MDS and its relation to serum Epo levels, and thereby analyze the medullary response to anemia, focusing on the percentage of erythroblasts in maturation stages I to IV, the expression of surface transferrin receptor (TfR, CD71) and the levels of hemoglobin (Hb) and ferritin.
Methods
We prospectively analyzed 57 newly-diagnosed MDS patients, focusing on MDS subtype; bone marrow morphology; and endogenous Epo levels, serum ferritin levels and Hb concentration at diagnosis. Flow cytometry was performed on all patients (CD45, CD34, CD117, HLA-DR, CD71, CD36, CD35, CD44 and CD105) and on 16 normal controls (samples collected during orthopedic surgery).
Results
Patients (63.2% female) had a mean age of 71.2±11.3 years (range: 22-89) and controls (68.8% female) had a mean age of 63±15; 70.2% of patients had RCMD, 8.8% had RCUD, 8.8% had RCRS, 7.0% had RAEB-1, 3.5% had RAEB-2 and 1.8% had 5q- syndrome; 35% of patients had Normal Epo, 53% had Mild elevations, 8% had Moderate and 4% had Marked elevations. There was no association between the percentage of erythroblasts (by flow or morphology) and the MDS subtype (p=NS), degree of dysplasia (p=NS), Epo levels (p=NS), ferritin levels (p=NS) or Hb levels (p=NS), nor between Epo levels and the MDS subtype (p=NS), although, as expected, there was an inverse correlation between Hb and Epo levels (r= -0.35, p=0.0014).There were no differences in the percentages of erythroblasts in stages I to IV between the normal marrow and MDS patients with Normal-to-Mildly elevated Epo levels (p=NS); however, there was a significant threefold increase in Stage I (2.2±1.0% vs 0.7±0.1%, p<0.001) and Stage II (4.8±2.9% vs 1.8±0.2%, p=0.02) erythroblasts in patients with Epo levels over 100 IU/L compared to patients with Epo<100 IU/L. There was a decrease in the expression of TfR in patients with MDS with Epo<100 IU/L compared to Epo>100 IU/L, for Stages I (p<0.001), II (p=0.019) and III (p<0.001), but not IV (p=NS), with patients with Epo>100 IU/L reaching a similar expression of transferrin receptor as normal marrows, across all stages (p=NS for I to IV).
Conclusion
There was an expected inverse correlation between Hb and Epo levels that, however, was not reflected in the percentage of erythroblasts in the bone marrow. The distribution of erythroblasts by maturation stage was identical in normal marrows and patients with MDS with normal to mildly elevated (<100 IU/L) Epo, as observed in the clinical model of response to exogenous Epo. The percentage of early stage erythroblasts increased in patients with Epo levels >100 IU/L, likely reflecting an increase in the commitment of CD34+ cells to the erythroid lineage. The expression of surface transferrin receptor decreased in all stages with Epo<100 IU/L compared to the normal marrow, with levels over 100 IU/L being necessary to obtain similar levels of expression of TfR to the normal marrow, possibly explaining the clinical model of increased likelihood of response to exogenous Epo in patients with levels <100 IU/L, and the fact that the expression of surface transferrin receptor is Epo-dependent both through transcriptional and post-transcriptional mechanisms.
Session topic: E-poster
Keyword(s): Erythropoieisis, Erythropoietin, Myelodysplasia, Transferrin receptor
Type: Publication Only
Background
Myelodysplastic syndromes (MDS) are characterized by peripheral citopenias within the context of a dysplastic, and frequently hypercellular bone marrow.Anemia is one of the most frequent findings, with 20 to 40% of patients responding to exogenous erythropoietin (Epo), with or without the addition of G-CSF, despite normal to elevated levels of serum endogenous Epo, reflecting the complexity of erythropoietic control in these syndromes. Nevertheless, a different likelihood of response to exogenous Epo has been identified between patients with Normal (<=20 IU/L), Mildly Elevated (20-100 IU/L), Moderately Elevated (100-500 IU/L) and Markedly Elevated (>500 IU/L) endogenous Epo levels.
Aims
To further characterize the early erythropoietic response in MDS and its relation to serum Epo levels, and thereby analyze the medullary response to anemia, focusing on the percentage of erythroblasts in maturation stages I to IV, the expression of surface transferrin receptor (TfR, CD71) and the levels of hemoglobin (Hb) and ferritin.
Methods
We prospectively analyzed 57 newly-diagnosed MDS patients, focusing on MDS subtype; bone marrow morphology; and endogenous Epo levels, serum ferritin levels and Hb concentration at diagnosis. Flow cytometry was performed on all patients (CD45, CD34, CD117, HLA-DR, CD71, CD36, CD35, CD44 and CD105) and on 16 normal controls (samples collected during orthopedic surgery).
Results
Patients (63.2% female) had a mean age of 71.2±11.3 years (range: 22-89) and controls (68.8% female) had a mean age of 63±15; 70.2% of patients had RCMD, 8.8% had RCUD, 8.8% had RCRS, 7.0% had RAEB-1, 3.5% had RAEB-2 and 1.8% had 5q- syndrome; 35% of patients had Normal Epo, 53% had Mild elevations, 8% had Moderate and 4% had Marked elevations. There was no association between the percentage of erythroblasts (by flow or morphology) and the MDS subtype (p=NS), degree of dysplasia (p=NS), Epo levels (p=NS), ferritin levels (p=NS) or Hb levels (p=NS), nor between Epo levels and the MDS subtype (p=NS), although, as expected, there was an inverse correlation between Hb and Epo levels (r= -0.35, p=0.0014).There were no differences in the percentages of erythroblasts in stages I to IV between the normal marrow and MDS patients with Normal-to-Mildly elevated Epo levels (p=NS); however, there was a significant threefold increase in Stage I (2.2±1.0% vs 0.7±0.1%, p<0.001) and Stage II (4.8±2.9% vs 1.8±0.2%, p=0.02) erythroblasts in patients with Epo levels over 100 IU/L compared to patients with Epo<100 IU/L. There was a decrease in the expression of TfR in patients with MDS with Epo<100 IU/L compared to Epo>100 IU/L, for Stages I (p<0.001), II (p=0.019) and III (p<0.001), but not IV (p=NS), with patients with Epo>100 IU/L reaching a similar expression of transferrin receptor as normal marrows, across all stages (p=NS for I to IV).
Conclusion
There was an expected inverse correlation between Hb and Epo levels that, however, was not reflected in the percentage of erythroblasts in the bone marrow. The distribution of erythroblasts by maturation stage was identical in normal marrows and patients with MDS with normal to mildly elevated (<100 IU/L) Epo, as observed in the clinical model of response to exogenous Epo. The percentage of early stage erythroblasts increased in patients with Epo levels >100 IU/L, likely reflecting an increase in the commitment of CD34+ cells to the erythroid lineage. The expression of surface transferrin receptor decreased in all stages with Epo<100 IU/L compared to the normal marrow, with levels over 100 IU/L being necessary to obtain similar levels of expression of TfR to the normal marrow, possibly explaining the clinical model of increased likelihood of response to exogenous Epo in patients with levels <100 IU/L, and the fact that the expression of surface transferrin receptor is Epo-dependent both through transcriptional and post-transcriptional mechanisms.
Session topic: E-poster
Keyword(s): Erythropoieisis, Erythropoietin, Myelodysplasia, Transferrin receptor
Abstract: PB1910
Type: Publication Only
Background
Myelodysplastic syndromes (MDS) are characterized by peripheral citopenias within the context of a dysplastic, and frequently hypercellular bone marrow.Anemia is one of the most frequent findings, with 20 to 40% of patients responding to exogenous erythropoietin (Epo), with or without the addition of G-CSF, despite normal to elevated levels of serum endogenous Epo, reflecting the complexity of erythropoietic control in these syndromes. Nevertheless, a different likelihood of response to exogenous Epo has been identified between patients with Normal (<=20 IU/L), Mildly Elevated (20-100 IU/L), Moderately Elevated (100-500 IU/L) and Markedly Elevated (>500 IU/L) endogenous Epo levels.
Aims
To further characterize the early erythropoietic response in MDS and its relation to serum Epo levels, and thereby analyze the medullary response to anemia, focusing on the percentage of erythroblasts in maturation stages I to IV, the expression of surface transferrin receptor (TfR, CD71) and the levels of hemoglobin (Hb) and ferritin.
Methods
We prospectively analyzed 57 newly-diagnosed MDS patients, focusing on MDS subtype; bone marrow morphology; and endogenous Epo levels, serum ferritin levels and Hb concentration at diagnosis. Flow cytometry was performed on all patients (CD45, CD34, CD117, HLA-DR, CD71, CD36, CD35, CD44 and CD105) and on 16 normal controls (samples collected during orthopedic surgery).
Results
Patients (63.2% female) had a mean age of 71.2±11.3 years (range: 22-89) and controls (68.8% female) had a mean age of 63±15; 70.2% of patients had RCMD, 8.8% had RCUD, 8.8% had RCRS, 7.0% had RAEB-1, 3.5% had RAEB-2 and 1.8% had 5q- syndrome; 35% of patients had Normal Epo, 53% had Mild elevations, 8% had Moderate and 4% had Marked elevations. There was no association between the percentage of erythroblasts (by flow or morphology) and the MDS subtype (p=NS), degree of dysplasia (p=NS), Epo levels (p=NS), ferritin levels (p=NS) or Hb levels (p=NS), nor between Epo levels and the MDS subtype (p=NS), although, as expected, there was an inverse correlation between Hb and Epo levels (r= -0.35, p=0.0014).There were no differences in the percentages of erythroblasts in stages I to IV between the normal marrow and MDS patients with Normal-to-Mildly elevated Epo levels (p=NS); however, there was a significant threefold increase in Stage I (2.2±1.0% vs 0.7±0.1%, p<0.001) and Stage II (4.8±2.9% vs 1.8±0.2%, p=0.02) erythroblasts in patients with Epo levels over 100 IU/L compared to patients with Epo<100 IU/L. There was a decrease in the expression of TfR in patients with MDS with Epo<100 IU/L compared to Epo>100 IU/L, for Stages I (p<0.001), II (p=0.019) and III (p<0.001), but not IV (p=NS), with patients with Epo>100 IU/L reaching a similar expression of transferrin receptor as normal marrows, across all stages (p=NS for I to IV).
Conclusion
There was an expected inverse correlation between Hb and Epo levels that, however, was not reflected in the percentage of erythroblasts in the bone marrow. The distribution of erythroblasts by maturation stage was identical in normal marrows and patients with MDS with normal to mildly elevated (<100 IU/L) Epo, as observed in the clinical model of response to exogenous Epo. The percentage of early stage erythroblasts increased in patients with Epo levels >100 IU/L, likely reflecting an increase in the commitment of CD34+ cells to the erythroid lineage. The expression of surface transferrin receptor decreased in all stages with Epo<100 IU/L compared to the normal marrow, with levels over 100 IU/L being necessary to obtain similar levels of expression of TfR to the normal marrow, possibly explaining the clinical model of increased likelihood of response to exogenous Epo in patients with levels <100 IU/L, and the fact that the expression of surface transferrin receptor is Epo-dependent both through transcriptional and post-transcriptional mechanisms.
Session topic: E-poster
Keyword(s): Erythropoieisis, Erythropoietin, Myelodysplasia, Transferrin receptor
Type: Publication Only
Background
Myelodysplastic syndromes (MDS) are characterized by peripheral citopenias within the context of a dysplastic, and frequently hypercellular bone marrow.Anemia is one of the most frequent findings, with 20 to 40% of patients responding to exogenous erythropoietin (Epo), with or without the addition of G-CSF, despite normal to elevated levels of serum endogenous Epo, reflecting the complexity of erythropoietic control in these syndromes. Nevertheless, a different likelihood of response to exogenous Epo has been identified between patients with Normal (<=20 IU/L), Mildly Elevated (20-100 IU/L), Moderately Elevated (100-500 IU/L) and Markedly Elevated (>500 IU/L) endogenous Epo levels.
Aims
To further characterize the early erythropoietic response in MDS and its relation to serum Epo levels, and thereby analyze the medullary response to anemia, focusing on the percentage of erythroblasts in maturation stages I to IV, the expression of surface transferrin receptor (TfR, CD71) and the levels of hemoglobin (Hb) and ferritin.
Methods
We prospectively analyzed 57 newly-diagnosed MDS patients, focusing on MDS subtype; bone marrow morphology; and endogenous Epo levels, serum ferritin levels and Hb concentration at diagnosis. Flow cytometry was performed on all patients (CD45, CD34, CD117, HLA-DR, CD71, CD36, CD35, CD44 and CD105) and on 16 normal controls (samples collected during orthopedic surgery).
Results
Patients (63.2% female) had a mean age of 71.2±11.3 years (range: 22-89) and controls (68.8% female) had a mean age of 63±15; 70.2% of patients had RCMD, 8.8% had RCUD, 8.8% had RCRS, 7.0% had RAEB-1, 3.5% had RAEB-2 and 1.8% had 5q- syndrome; 35% of patients had Normal Epo, 53% had Mild elevations, 8% had Moderate and 4% had Marked elevations. There was no association between the percentage of erythroblasts (by flow or morphology) and the MDS subtype (p=NS), degree of dysplasia (p=NS), Epo levels (p=NS), ferritin levels (p=NS) or Hb levels (p=NS), nor between Epo levels and the MDS subtype (p=NS), although, as expected, there was an inverse correlation between Hb and Epo levels (r= -0.35, p=0.0014).There were no differences in the percentages of erythroblasts in stages I to IV between the normal marrow and MDS patients with Normal-to-Mildly elevated Epo levels (p=NS); however, there was a significant threefold increase in Stage I (2.2±1.0% vs 0.7±0.1%, p<0.001) and Stage II (4.8±2.9% vs 1.8±0.2%, p=0.02) erythroblasts in patients with Epo levels over 100 IU/L compared to patients with Epo<100 IU/L. There was a decrease in the expression of TfR in patients with MDS with Epo<100 IU/L compared to Epo>100 IU/L, for Stages I (p<0.001), II (p=0.019) and III (p<0.001), but not IV (p=NS), with patients with Epo>100 IU/L reaching a similar expression of transferrin receptor as normal marrows, across all stages (p=NS for I to IV).
Conclusion
There was an expected inverse correlation between Hb and Epo levels that, however, was not reflected in the percentage of erythroblasts in the bone marrow. The distribution of erythroblasts by maturation stage was identical in normal marrows and patients with MDS with normal to mildly elevated (<100 IU/L) Epo, as observed in the clinical model of response to exogenous Epo. The percentage of early stage erythroblasts increased in patients with Epo levels >100 IU/L, likely reflecting an increase in the commitment of CD34+ cells to the erythroid lineage. The expression of surface transferrin receptor decreased in all stages with Epo<100 IU/L compared to the normal marrow, with levels over 100 IU/L being necessary to obtain similar levels of expression of TfR to the normal marrow, possibly explaining the clinical model of increased likelihood of response to exogenous Epo in patients with levels <100 IU/L, and the fact that the expression of surface transferrin receptor is Epo-dependent both through transcriptional and post-transcriptional mechanisms.
Session topic: E-poster
Keyword(s): Erythropoieisis, Erythropoietin, Myelodysplasia, Transferrin receptor
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