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102 IRON CHELATION THERAPY IMPROVES HAEMATOLOGICAL RESPONSE IN HIGH-RISK MYELODYSPLASTIC PATIENTS TREATED WITH AZACITIDINE
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Poster Presentations – 13th International Symposium on Myelodyspastic Syndromes / Leukemia Research 39 S1 (2015) S1–S166
microenvironment and stimulate hematopoiesis; and c) T regulatory cells, which possess anti-inflammatory properties. Herein we present a trial in progress. We have filed an IND for our study in which we will seek to determine the safety and potential efficacy of intravenously administered autologous SVF cells in 10 patients with severe aplastic anemia that is refractory to immune suppressive therapy. Clinical endpoints will include complete response (CR), defined as a neutrophil count greater than 1.5 × 109/L, a platelet count greater than 150 × 109/L, and a hemoglobin level of greater than 110 g/L (11.0 g/dL). Partial response (PR) is defined by transfusion independence and no longer meeting criteria for severe disease. Relapse is indicated by the requirement for blood transfusion. Toxicity of treatment will be evaluated for the duration of the study and will be graded according to the criteria of the World Health Organization Patients will receive an intravenous injection of 100 million autologous SVF collected from 500 cc of adipose tissue on the same day as the liposuction. Patients yielding less than 100 million SVF cells will be excluded. Patients will also receive cyclosporin A 5mg/ kg PO for 6 months during the study. Evaluation of bone marrow will be performed pretreatment and at 6 months after treatment, whereas assessment of safety and efficacy will be performed at 1, 3, and 6 months, consisting of blood counts, need for transfusions. Scientific background/rationale for the trial and trial design will be discussed in further depth.
102 IRON CHELATION THERAPY IMPROVES HAEMATOLOGICAL RESPONSE IN HIGH-RISK MYELODYSPLASTIC PATIENTS TREATED WITH AZACITIDINE S. Improta1, P. Della Cioppa1, M. Esposito1, A. Gagliardi1, A. Lucania1, G. Nitrato Izzo1, M.R. Villa1, L. Mastrullo1 1 Haematology Unit, San Gennaro Hospital, Napoli, Italy Fig. 1. The CC-486 Quazar Lower-Risk MDS Trial: study design.
patients; as of January, 2015, 66 patients (17%) have enrolled. The expected trial duration is ~60 months.
101 HEMAXELLERATE I™, AUTOLOGOUS ADIPOSE STROMAL VASCULAR FRACTION CELLS, FOR SEVERE APLASTIC ANEMIA T. Ichim1, A. Patel2, D. Koos1, C. Ichim1 1 Cellular and Molecular Therapeutics, Regen BioPharma Inc., San Diego, USA; 2Director of Cardiovascular Regenerative Medicine, University of Utah, Salt Lake City, USA Aplastic anemia, defined by pancytopenia with a hypocellular bone marrow, is believed to be the result of immunological attack on the bone marrow microenvironment. The relevance of the immune system in this condition is suggested by the following lines of evidence: a) the efficacy of treatment with immune suppressive drugs, which is 60-80% with 5 year survival rates of approximately 75%; b) the presence of immune cell infiltrates in the bone marrow of patients; c) the upregulation of Th1/Th17 cytokines in patients; and d) the presence of abnormally low levels of immune regulatory T cells in patients with aplastic anemia as compared with controls. Stromal Vascular Fraction (SVF) preparations contain significant numbers of cellular populations with therapeutic activity that would be relevant to aplastic anemia; namely, a) mesenchymal stem cells (MSC), which suppress pathological immune responses and accelerate hematopoiesis; b) endothelial cells, which assist in repairing damaged bone marrow hematopoietic
Background: The goals of treating older patients with myelodysplastic syndrome (MDS) are different than for younger patients. Few elderly patients are able to pursue an allogeneic stem cell transplant. Azacitidine (AZA) improves long-term outcomes of higher-risk MDS patients and is now the reference frontline therapy of higher-risk MDS not eligible for allogeneic stem cell transplant. Anaemia is the most common symptom of MDS and most patients become transfusion-dependent with the risk of iron overload. Deferasirox is an orally available iron chelator administered once-daily in transfusion-dependent patients with various chronic anaemias. Its efficacy has been established in controlled clinical trials. Aim: We report our experience on using the azacitidine in patients with high-risk MDS, evaluating the efficacy and safety. Concomitant treatment with deferasirox was performed in a routine clinical setting following Consensus Guidelines on Iron Chelation Therapy. Methods: In our Institution from October 2009 to December 2014 we have treated 29 elderly patients (19 male and 10 female, median age 76 years, r. 72-88) affected by HIGH-RISK MDS (IPSS INT-2/HIGH). Patients received subcutaneous azacitidine at 75mg/ m2 daily for 7 days every 4 weeks. All patients completed at least 6 cycles of therapy. 11/29 (38%) patients underwent more than 8 cycles of therapy. 17/29 patients underwent as well iron chelation therapy with deferasirox receiving a starting dosage of 10 mg/ kg/day, subsequently titrated according to serum ferritin (SF) measured monthly. Results: Complete response (CR), partial response (PR), and hematologic improvement (HI) were observed in 2 (7%), 5 (21%), and 11 (38%) patients, respectively. The median number of cycles to clinical response was 4 (range 4-8). The 2-year rate of acute
Poster Presentations – 13th International Symposium on Myelodyspastic Syndromes / Leukemia Research 39 S1 (2015) S1–S166
myeloid leukemia-free survival was 48%. Five serious adverse events occurred in five patients with one fatal outcome. 15 out of 18 patients who showed any hematologic response (CR+PR+HI) meeting International Working Group 2006 criteria had also performed deferasirox therapy. No increased toxicity was noted when deferasirox was used concomitantly with azacitidine. Conclusions: Our results confirm the effectiveness of the therapy with azacitidine in HIGH-RISK MDS elderly patients with acceptable toxicity profile. Peripheral cytopenias were the most commonly occurring adverse event, with gastrointestinal adverse events and injection-site reactions among the most commonly occurring non-haematological adverse events. In conclusion, azacitidine is an important agent for use in the treatment of elderly patients with MDS. Furthermore concurrent use of deferasirox in patients with iron overload seems to significantly improve the hematologic response by reducing transfusion requirement.
103 AZACITIDINE TREATMENT OF HIGH RISK MDS AND AML, ANALYSIS OF LONG RESPONDING PATIENTS AND PROGNOSTIC FACTORS OF OVERALL SURVIVAL, CZECH MDS GROUP EXPERIENCE A. Jonasova1, J. Cermak2, L. Cervinek3, P. Belohlavkova4, O. Cerna5, K. Kacmarova6, E. Janousova7 1 1 medical departmen hematology, General University Hospital and 1st School of Medicine Charles University, Prague, Czech Republic; 21 medical departmen hematology, Institute of hematology and blood transfusion, Prague, Czech Republic; 3Hematology, University Hospital Brno, Brno, Czech Republic; 4Hematology, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic; 5 Hematology, University Hospital Kralovske Vynohrady III. school of medcine, Prague, Czech Republic; 6Hematology, Czech MDS group, Prague, Czech Republic; 7Biostatistic, Institute of biostatistics, Brno, Czech Republic Introduction: Demethylating agents, especially 5-azacitidine, are currently considered first line treatment for high risk MDS patients. We present a comparison to the historical Czech MDS group treated by standard therapy, and analyze long responding patients and prognostic clinical markers in relation to overall survival (OS). Patients and results: Between 12/2008 and 1/2014 azacitidine was used to treat 162 patients, 99 males and 63 females, median age 69 years (range 49-88) with diagnosis: 6 RCMD, 23 RAEB – I, 85 RAEB II, 29 AML <30% MB, 16 CMML II, 1 MDS/MPS and 2 U-MDS unclassifiable. 19 patients had secondary MDS. Azacitidine was first line treatment in 77%. Median follow-up was 14 months (range 1-56), median number of cycles was 7 (range 1-34). 42% patients belonged to good risk cytogenetic group (32% with normal karyotype), 22% to intermediate and 25% to poor risk group. Common adverse events included hematologic toxicity with neutropenia grade (Gr) 3/4 in 54.9% and thrombocytopenia Gr 3/4 in 70,3%, Nonhematologic side effects, mostly Gr1/2, were gastrointestinal in 21.6%, local reactions and fatigue in 31.5%. Overall response rate (ORR) was 43.2% (CR 18.5%, CRi 7.1%, PR 17.3%) stable disease (SD) was reached in 16% and hematology improvement (HI) was 53.1%. After 12 months, on the basis of Kaplan-Meier estimates, 67.8% of patients were alive and median overall survival (OS) was 16.4 months. We also analyzed historical data from a group treated with convention therapy. The one year survival was 29% and median OS was 7.5 months. We analyze several clinical parameters collected at the start of azacitidine as prognostic factors for OS. Statistically significant are ECOG PS, cytogenetic and absolute neutrophil count (p≤0.001), platelet count with (p=0.006) and reaching CR and CRi (p=0.001).
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Interestingly, patients with complex cytogenetic abnormalities with 5q- (median survival 7 months) had the worst outcome, whereas 26 long-surviving patients did not differ in WHO dg, IPSS, primary versus secondary MDS, age, or sex. As expected 84.2% had good and intermediate cytogenetics and less advanced cytopenias at the beginning of treatment. Conclusion: Our results correlate well with other published data (AZA 001, CALGB 9221). OS data are comparable with other “real life” studies. Statistically significant for OS, indicating best responders, were: cytogenetic aberration, platelet and neutrophil count, ECOG PS and achieving CR. Supported by Charles University grant PRVOUK 24/27, and Czech Ministry of Health grant NT14174-3.
104 APG101 (SOLUBLE CD95-FC) IMPROVES BFU-E GROWTH IN LOWER RISK MYELODYSPLASTIC SYNDROME WITH COLLAPSED ERYTHROPOIESIS: A PRECLINICAL STUDY A. Raimbault1, S. Bondu2, C. Pierre-Eugene2, C. Deudon1, L. Willems1, E. Frisan1, N. Chapuis1, R. Sapena3, A. Rouquette4, C. Kunz5, H. Fricke5, O. Kosmider1, V. Bardet1, M. Fontenay1 1 Hematology, Cochin Institute Inserm U1016 - APHP, Paris, France; 2 Hematology, Cochin Institute Inserm U1016, Paris, France; 3 Hematology, Henri Mondor Hospital - APHP, Creteil, France; 4 Biostatistics department, Cochin Hospital - APHP, Paris, France; 5 Research department, APOGENIX - GmbH, Heidelberg, Germany Introduction: Production of red blood cells is negatively regulated by caspase-dependent apoptosis of immature precursors mediated by death receptor CD95 when activated by its ligand, CD95L,. In the bone marrow. CD95 is overexpressed on CD34+ progenitors in two thirds of patients with low/int-1 risk myelodysplastic syndromes (MDS), and this contributes to anemia. CD95 overexpression may depend on methylation level and on SNP located at -1377 and -670 from ATG in the 5’UTR of CD95 promoter. We have previously reported that resistance to erythropoiesis-stimulating agents (ESA) was significantly associated with CD95 overexpression and poor residual erythropoiesis. In a preclinical study, we investigated an alternative therapeutic strategy for anemia in lower risk MDS based on inhibition of CD95-dependent apoptosis of erythroid precursors. Patients and methods: From a cohort of 250 MDS patients and 30 controls, CD95 and CD95L expression was quantified by flow cytometry. SNP rs2234767 (-1377G>A) and rs1800682 (-670A>G) were determined by Sanger sequencing. The effect of APG101, a fusion protein consisting of the extracellular domain of human CD95 and Fc fragment of human IgG1, on erythropoiesis was investigated in 20 low/int-1 MDS and 6 control bone marrows other than MDS in liquid cultures and/or clonogenic assays. Results: CD95 and CD95L were overexpressed in 146/250 (58%) and in 48/82 (58%) MDS, respectively. In 147 samples, we showed that the -1377G allele, to which the transcription factor SP1 can bind, was more frequent in MDS compared to controls and that -1377G/670A haplotype was associated with a higher CD95 expression level than -1377A/-670G ancestral haplotype (P=0.042). CD95L epigenetic regulation is currently under study. In liquid cultures, APG101 increased the number of erythroid progenitors of BFU-E type and the proliferation of erythroblasts by inhibiting apoptosis of immature precursors in 4 MDS samples, but not in 3 controls. In a series of 20 MDS with high CD95 expression level, APG101 improved the growth of bone marrow mononuclear cell (BMMC)derived BFU-E in 15/20 MDS patients which erythropoiesis was initially collapsed (≤15 BFU-E/105 BMMC), independently of CD95L level. APG101 had no effect on BFU-E number of control samples. APG101 did not increase the expansion of non-erythroid leukemic clusters counted at day 7 of clonogenic assays.
Poster Presentations – 13th International Symposium on Myelodyspastic Syndromes / Leukemia Research 39 S1 (2015) S1–S166
microenvironment and stimulate hematopoiesis; and c) T regulatory cells, which possess anti-inflammatory properties. Herein we present a trial in progress. We have filed an IND for our study in which we will seek to determine the safety and potential efficacy of intravenously administered autologous SVF cells in 10 patients with severe aplastic anemia that is refractory to immune suppressive therapy. Clinical endpoints will include complete response (CR), defined as a neutrophil count greater than 1.5 × 109/L, a platelet count greater than 150 × 109/L, and a hemoglobin level of greater than 110 g/L (11.0 g/dL). Partial response (PR) is defined by transfusion independence and no longer meeting criteria for severe disease. Relapse is indicated by the requirement for blood transfusion. Toxicity of treatment will be evaluated for the duration of the study and will be graded according to the criteria of the World Health Organization Patients will receive an intravenous injection of 100 million autologous SVF collected from 500 cc of adipose tissue on the same day as the liposuction. Patients yielding less than 100 million SVF cells will be excluded. Patients will also receive cyclosporin A 5mg/ kg PO for 6 months during the study. Evaluation of bone marrow will be performed pretreatment and at 6 months after treatment, whereas assessment of safety and efficacy will be performed at 1, 3, and 6 months, consisting of blood counts, need for transfusions. Scientific background/rationale for the trial and trial design will be discussed in further depth.
102 IRON CHELATION THERAPY IMPROVES HAEMATOLOGICAL RESPONSE IN HIGH-RISK MYELODYSPLASTIC PATIENTS TREATED WITH AZACITIDINE S. Improta1, P. Della Cioppa1, M. Esposito1, A. Gagliardi1, A. Lucania1, G. Nitrato Izzo1, M.R. Villa1, L. Mastrullo1 1 Haematology Unit, San Gennaro Hospital, Napoli, Italy Fig. 1. The CC-486 Quazar Lower-Risk MDS Trial: study design.
patients; as of January, 2015, 66 patients (17%) have enrolled. The expected trial duration is ~60 months.
101 HEMAXELLERATE I™, AUTOLOGOUS ADIPOSE STROMAL VASCULAR FRACTION CELLS, FOR SEVERE APLASTIC ANEMIA T. Ichim1, A. Patel2, D. Koos1, C. Ichim1 1 Cellular and Molecular Therapeutics, Regen BioPharma Inc., San Diego, USA; 2Director of Cardiovascular Regenerative Medicine, University of Utah, Salt Lake City, USA Aplastic anemia, defined by pancytopenia with a hypocellular bone marrow, is believed to be the result of immunological attack on the bone marrow microenvironment. The relevance of the immune system in this condition is suggested by the following lines of evidence: a) the efficacy of treatment with immune suppressive drugs, which is 60-80% with 5 year survival rates of approximately 75%; b) the presence of immune cell infiltrates in the bone marrow of patients; c) the upregulation of Th1/Th17 cytokines in patients; and d) the presence of abnormally low levels of immune regulatory T cells in patients with aplastic anemia as compared with controls. Stromal Vascular Fraction (SVF) preparations contain significant numbers of cellular populations with therapeutic activity that would be relevant to aplastic anemia; namely, a) mesenchymal stem cells (MSC), which suppress pathological immune responses and accelerate hematopoiesis; b) endothelial cells, which assist in repairing damaged bone marrow hematopoietic
Background: The goals of treating older patients with myelodysplastic syndrome (MDS) are different than for younger patients. Few elderly patients are able to pursue an allogeneic stem cell transplant. Azacitidine (AZA) improves long-term outcomes of higher-risk MDS patients and is now the reference frontline therapy of higher-risk MDS not eligible for allogeneic stem cell transplant. Anaemia is the most common symptom of MDS and most patients become transfusion-dependent with the risk of iron overload. Deferasirox is an orally available iron chelator administered once-daily in transfusion-dependent patients with various chronic anaemias. Its efficacy has been established in controlled clinical trials. Aim: We report our experience on using the azacitidine in patients with high-risk MDS, evaluating the efficacy and safety. Concomitant treatment with deferasirox was performed in a routine clinical setting following Consensus Guidelines on Iron Chelation Therapy. Methods: In our Institution from October 2009 to December 2014 we have treated 29 elderly patients (19 male and 10 female, median age 76 years, r. 72-88) affected by HIGH-RISK MDS (IPSS INT-2/HIGH). Patients received subcutaneous azacitidine at 75mg/ m2 daily for 7 days every 4 weeks. All patients completed at least 6 cycles of therapy. 11/29 (38%) patients underwent more than 8 cycles of therapy. 17/29 patients underwent as well iron chelation therapy with deferasirox receiving a starting dosage of 10 mg/ kg/day, subsequently titrated according to serum ferritin (SF) measured monthly. Results: Complete response (CR), partial response (PR), and hematologic improvement (HI) were observed in 2 (7%), 5 (21%), and 11 (38%) patients, respectively. The median number of cycles to clinical response was 4 (range 4-8). The 2-year rate of acute
Poster Presentations – 13th International Symposium on Myelodyspastic Syndromes / Leukemia Research 39 S1 (2015) S1–S166
myeloid leukemia-free survival was 48%. Five serious adverse events occurred in five patients with one fatal outcome. 15 out of 18 patients who showed any hematologic response (CR+PR+HI) meeting International Working Group 2006 criteria had also performed deferasirox therapy. No increased toxicity was noted when deferasirox was used concomitantly with azacitidine. Conclusions: Our results confirm the effectiveness of the therapy with azacitidine in HIGH-RISK MDS elderly patients with acceptable toxicity profile. Peripheral cytopenias were the most commonly occurring adverse event, with gastrointestinal adverse events and injection-site reactions among the most commonly occurring non-haematological adverse events. In conclusion, azacitidine is an important agent for use in the treatment of elderly patients with MDS. Furthermore concurrent use of deferasirox in patients with iron overload seems to significantly improve the hematologic response by reducing transfusion requirement.
103 AZACITIDINE TREATMENT OF HIGH RISK MDS AND AML, ANALYSIS OF LONG RESPONDING PATIENTS AND PROGNOSTIC FACTORS OF OVERALL SURVIVAL, CZECH MDS GROUP EXPERIENCE A. Jonasova1, J. Cermak2, L. Cervinek3, P. Belohlavkova4, O. Cerna5, K. Kacmarova6, E. Janousova7 1 1 medical departmen hematology, General University Hospital and 1st School of Medicine Charles University, Prague, Czech Republic; 21 medical departmen hematology, Institute of hematology and blood transfusion, Prague, Czech Republic; 3Hematology, University Hospital Brno, Brno, Czech Republic; 4Hematology, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic; 5 Hematology, University Hospital Kralovske Vynohrady III. school of medcine, Prague, Czech Republic; 6Hematology, Czech MDS group, Prague, Czech Republic; 7Biostatistic, Institute of biostatistics, Brno, Czech Republic Introduction: Demethylating agents, especially 5-azacitidine, are currently considered first line treatment for high risk MDS patients. We present a comparison to the historical Czech MDS group treated by standard therapy, and analyze long responding patients and prognostic clinical markers in relation to overall survival (OS). Patients and results: Between 12/2008 and 1/2014 azacitidine was used to treat 162 patients, 99 males and 63 females, median age 69 years (range 49-88) with diagnosis: 6 RCMD, 23 RAEB – I, 85 RAEB II, 29 AML <30% MB, 16 CMML II, 1 MDS/MPS and 2 U-MDS unclassifiable. 19 patients had secondary MDS. Azacitidine was first line treatment in 77%. Median follow-up was 14 months (range 1-56), median number of cycles was 7 (range 1-34). 42% patients belonged to good risk cytogenetic group (32% with normal karyotype), 22% to intermediate and 25% to poor risk group. Common adverse events included hematologic toxicity with neutropenia grade (Gr) 3/4 in 54.9% and thrombocytopenia Gr 3/4 in 70,3%, Nonhematologic side effects, mostly Gr1/2, were gastrointestinal in 21.6%, local reactions and fatigue in 31.5%. Overall response rate (ORR) was 43.2% (CR 18.5%, CRi 7.1%, PR 17.3%) stable disease (SD) was reached in 16% and hematology improvement (HI) was 53.1%. After 12 months, on the basis of Kaplan-Meier estimates, 67.8% of patients were alive and median overall survival (OS) was 16.4 months. We also analyzed historical data from a group treated with convention therapy. The one year survival was 29% and median OS was 7.5 months. We analyze several clinical parameters collected at the start of azacitidine as prognostic factors for OS. Statistically significant are ECOG PS, cytogenetic and absolute neutrophil count (p≤0.001), platelet count with (p=0.006) and reaching CR and CRi (p=0.001).
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Interestingly, patients with complex cytogenetic abnormalities with 5q- (median survival 7 months) had the worst outcome, whereas 26 long-surviving patients did not differ in WHO dg, IPSS, primary versus secondary MDS, age, or sex. As expected 84.2% had good and intermediate cytogenetics and less advanced cytopenias at the beginning of treatment. Conclusion: Our results correlate well with other published data (AZA 001, CALGB 9221). OS data are comparable with other “real life” studies. Statistically significant for OS, indicating best responders, were: cytogenetic aberration, platelet and neutrophil count, ECOG PS and achieving CR. Supported by Charles University grant PRVOUK 24/27, and Czech Ministry of Health grant NT14174-3.
104 APG101 (SOLUBLE CD95-FC) IMPROVES BFU-E GROWTH IN LOWER RISK MYELODYSPLASTIC SYNDROME WITH COLLAPSED ERYTHROPOIESIS: A PRECLINICAL STUDY A. Raimbault1, S. Bondu2, C. Pierre-Eugene2, C. Deudon1, L. Willems1, E. Frisan1, N. Chapuis1, R. Sapena3, A. Rouquette4, C. Kunz5, H. Fricke5, O. Kosmider1, V. Bardet1, M. Fontenay1 1 Hematology, Cochin Institute Inserm U1016 - APHP, Paris, France; 2 Hematology, Cochin Institute Inserm U1016, Paris, France; 3 Hematology, Henri Mondor Hospital - APHP, Creteil, France; 4 Biostatistics department, Cochin Hospital - APHP, Paris, France; 5 Research department, APOGENIX - GmbH, Heidelberg, Germany Introduction: Production of red blood cells is negatively regulated by caspase-dependent apoptosis of immature precursors mediated by death receptor CD95 when activated by its ligand, CD95L,. In the bone marrow. CD95 is overexpressed on CD34+ progenitors in two thirds of patients with low/int-1 risk myelodysplastic syndromes (MDS), and this contributes to anemia. CD95 overexpression may depend on methylation level and on SNP located at -1377 and -670 from ATG in the 5’UTR of CD95 promoter. We have previously reported that resistance to erythropoiesis-stimulating agents (ESA) was significantly associated with CD95 overexpression and poor residual erythropoiesis. In a preclinical study, we investigated an alternative therapeutic strategy for anemia in lower risk MDS based on inhibition of CD95-dependent apoptosis of erythroid precursors. Patients and methods: From a cohort of 250 MDS patients and 30 controls, CD95 and CD95L expression was quantified by flow cytometry. SNP rs2234767 (-1377G>A) and rs1800682 (-670A>G) were determined by Sanger sequencing. The effect of APG101, a fusion protein consisting of the extracellular domain of human CD95 and Fc fragment of human IgG1, on erythropoiesis was investigated in 20 low/int-1 MDS and 6 control bone marrows other than MDS in liquid cultures and/or clonogenic assays. Results: CD95 and CD95L were overexpressed in 146/250 (58%) and in 48/82 (58%) MDS, respectively. In 147 samples, we showed that the -1377G allele, to which the transcription factor SP1 can bind, was more frequent in MDS compared to controls and that -1377G/670A haplotype was associated with a higher CD95 expression level than -1377A/-670G ancestral haplotype (P=0.042). CD95L epigenetic regulation is currently under study. In liquid cultures, APG101 increased the number of erythroid progenitors of BFU-E type and the proliferation of erythroblasts by inhibiting apoptosis of immature precursors in 4 MDS samples, but not in 3 controls. In a series of 20 MDS with high CD95 expression level, APG101 improved the growth of bone marrow mononuclear cell (BMMC)derived BFU-E in 15/20 MDS patients which erythropoiesis was initially collapsed (≤15 BFU-E/105 BMMC), independently of CD95L level. APG101 had no effect on BFU-E number of control samples. APG101 did not increase the expansion of non-erythroid leukemic clusters counted at day 7 of clonogenic assays.