Clinical activity of azacitidine in patients who relapse after allogeneic stem cell transplantation for acute myeloid leukemia

Charles Craddock; Myriam Labopin; Marie Robin; Juergen Finke; Patrice Chevallier; Ibrahim Yakoub-Agha; Jean Henri Bourhis; Henrik Sengelov; Didier Blaise; Thomas Luft; Michael Hallek; Nicolaus Kroeger; Arnon Nagler; Mohamad Mohty

doi:10.3324/haematol.2015.140996

Clinical activity of azacitidine in patients who relapse after allogeneic stem cell transplantation for acute myeloid leukemia

Charles Craddock, Myriam Labopin, Marie Robin, Juergen Finke, Patrice Chevallier, Ibrahim Yakoub-Agha, Jean Henri Bourhis, Henrik Sengelov, Didier Blaise, Thomas Luft, Michael Hallek, Nicolaus Kroeger, Arnon Nagler, Mohamad Mohty

Department of Clinical Medicine

72 Citations (Scopus)

Abstract

Disease relapse is the most common cause of treatment failure after allogeneic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndromes, yet treatment options for such patients remain extremely limited. Azacitidine is an important new therapy in high-risk myelodysplastic syndromes and acute myeloid leukemia but its role in patients who relapse post allograft has not been defined. We studied the tolerability and activity of azacitidine in 181 patients who relapsed after an allograft for acute myeloid leukemia (n=116) or myelodysplastic syndromes (n=65). Sixty-nine patients received additional donor lymphocyte infusions. Forty-six of 157 (25%) assessable patients responded to azacitidine therapy: 24 (15%) achieved a complete remission and 22 a partial remission. Response rates were higher in patients transplanted in complete remission (P=0.04) and those transplanted for myelodysplastic syndromes (P=0.023). In patients who achieved a complete remission, the 2-year overall survival was 48% versus 12% for the whole population. Overall survival was determined by time to relapse post transplant more than six months (P=0.001) and percentage of blasts in the bone marrow at time of relapse (P=0.01). The concurrent administration of donor lymphocyte infusion did not improve either response rates or overall survival in patients treated with azacitidine. An azacitidine relapse prognostic score was developed which predicted 2-year overall survival ranging from 3%-37% (P=0.00001). We conclude that azacitidine represents an important new therapy in selected patients with acute myeloid leukemia/myelodysplastic syndromes who relapse after allogeneic stem cell transplantation. Prospective studies to confirm optimal treatment options in this challenging patient population are required.

Original language	English
Journal	Haematologica
Volume	101
Issue number	7
Pages (from-to)	879-83
Number of pages	5
ISSN	0390-6078
DOIs	https://doi.org/10.3324/haematol.2015.140996
Publication status	Published - Jul 2016

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10.3324/haematol.2015.140996

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Craddock, C., Labopin, M., Robin, M., Finke, J., Chevallier, P., Yakoub-Agha, I., Bourhis, J. H., Sengelov, H., Blaise, D., Luft, T., Hallek, M., Kroeger, N., Nagler, A., & Mohty, M. (2016). Clinical activity of azacitidine in patients who relapse after allogeneic stem cell transplantation for acute myeloid leukemia. Haematologica, 101(7), 879-83. https://doi.org/10.3324/haematol.2015.140996

Craddock, C, Labopin, M, Robin, M, Finke, J, Chevallier, P, Yakoub-Agha, I, Bourhis, JH, Sengelov, H, Blaise, D, Luft, T, Hallek, M, Kroeger, N, Nagler, A & Mohty, M 2016, 'Clinical activity of azacitidine in patients who relapse after allogeneic stem cell transplantation for acute myeloid leukemia', Haematologica, vol. 101, no. 7, pp. 879-83. https://doi.org/10.3324/haematol.2015.140996

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abstract = "Disease relapse is the most common cause of treatment failure after allogeneic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndromes, yet treatment options for such patients remain extremely limited. Azacitidine is an important new therapy in high-risk myelodysplastic syndromes and acute myeloid leukemia but its role in patients who relapse post allograft has not been defined. We studied the tolerability and activity of azacitidine in 181 patients who relapsed after an allograft for acute myeloid leukemia (n=116) or myelodysplastic syndromes (n=65). Sixty-nine patients received additional donor lymphocyte infusions. Forty-six of 157 (25%) assessable patients responded to azacitidine therapy: 24 (15%) achieved a complete remission and 22 a partial remission. Response rates were higher in patients transplanted in complete remission (P=0.04) and those transplanted for myelodysplastic syndromes (P=0.023). In patients who achieved a complete remission, the 2-year overall survival was 48% versus 12% for the whole population. Overall survival was determined by time to relapse post transplant more than six months (P=0.001) and percentage of blasts in the bone marrow at time of relapse (P=0.01). The concurrent administration of donor lymphocyte infusion did not improve either response rates or overall survival in patients treated with azacitidine. An azacitidine relapse prognostic score was developed which predicted 2-year overall survival ranging from 3%-37% (P=0.00001). We conclude that azacitidine represents an important new therapy in selected patients with acute myeloid leukemia/myelodysplastic syndromes who relapse after allogeneic stem cell transplantation. Prospective studies to confirm optimal treatment options in this challenging patient population are required.",

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T1 - Clinical activity of azacitidine in patients who relapse after allogeneic stem cell transplantation for acute myeloid leukemia

AU - Craddock, Charles

AU - Labopin, Myriam

AU - Robin, Marie

AU - Finke, Juergen

AU - Chevallier, Patrice

AU - Yakoub-Agha, Ibrahim

AU - Bourhis, Jean Henri

AU - Sengelov, Henrik

AU - Blaise, Didier

AU - Luft, Thomas

AU - Hallek, Michael

AU - Kroeger, Nicolaus

AU - Nagler, Arnon

AU - Mohty, Mohamad

PY - 2016/7

Y1 - 2016/7

N2 - Disease relapse is the most common cause of treatment failure after allogeneic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndromes, yet treatment options for such patients remain extremely limited. Azacitidine is an important new therapy in high-risk myelodysplastic syndromes and acute myeloid leukemia but its role in patients who relapse post allograft has not been defined. We studied the tolerability and activity of azacitidine in 181 patients who relapsed after an allograft for acute myeloid leukemia (n=116) or myelodysplastic syndromes (n=65). Sixty-nine patients received additional donor lymphocyte infusions. Forty-six of 157 (25%) assessable patients responded to azacitidine therapy: 24 (15%) achieved a complete remission and 22 a partial remission. Response rates were higher in patients transplanted in complete remission (P=0.04) and those transplanted for myelodysplastic syndromes (P=0.023). In patients who achieved a complete remission, the 2-year overall survival was 48% versus 12% for the whole population. Overall survival was determined by time to relapse post transplant more than six months (P=0.001) and percentage of blasts in the bone marrow at time of relapse (P=0.01). The concurrent administration of donor lymphocyte infusion did not improve either response rates or overall survival in patients treated with azacitidine. An azacitidine relapse prognostic score was developed which predicted 2-year overall survival ranging from 3%-37% (P=0.00001). We conclude that azacitidine represents an important new therapy in selected patients with acute myeloid leukemia/myelodysplastic syndromes who relapse after allogeneic stem cell transplantation. Prospective studies to confirm optimal treatment options in this challenging patient population are required.

AB - Disease relapse is the most common cause of treatment failure after allogeneic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndromes, yet treatment options for such patients remain extremely limited. Azacitidine is an important new therapy in high-risk myelodysplastic syndromes and acute myeloid leukemia but its role in patients who relapse post allograft has not been defined. We studied the tolerability and activity of azacitidine in 181 patients who relapsed after an allograft for acute myeloid leukemia (n=116) or myelodysplastic syndromes (n=65). Sixty-nine patients received additional donor lymphocyte infusions. Forty-six of 157 (25%) assessable patients responded to azacitidine therapy: 24 (15%) achieved a complete remission and 22 a partial remission. Response rates were higher in patients transplanted in complete remission (P=0.04) and those transplanted for myelodysplastic syndromes (P=0.023). In patients who achieved a complete remission, the 2-year overall survival was 48% versus 12% for the whole population. Overall survival was determined by time to relapse post transplant more than six months (P=0.001) and percentage of blasts in the bone marrow at time of relapse (P=0.01). The concurrent administration of donor lymphocyte infusion did not improve either response rates or overall survival in patients treated with azacitidine. An azacitidine relapse prognostic score was developed which predicted 2-year overall survival ranging from 3%-37% (P=0.00001). We conclude that azacitidine represents an important new therapy in selected patients with acute myeloid leukemia/myelodysplastic syndromes who relapse after allogeneic stem cell transplantation. Prospective studies to confirm optimal treatment options in this challenging patient population are required.

KW - Journal Article

U2 - 10.3324/haematol.2015.140996

DO - 10.3324/haematol.2015.140996

M3 - Journal article

C2 - 27081178

SN - 0390-6078

VL - 101

SP - 879

EP - 883

JO - Haematologica

JF - Haematologica

IS - 7

ER -

Clinical activity of azacitidine in patients who relapse after allogeneic stem cell transplantation for acute myeloid leukemia

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