Salvage Therapy Using Azacitidine for Relapsed Primary Myelofibrosis after Cord Blood Transplantation
We present the case of a 53-year-old woman with prefibrotic stage primary myelofibrosis (PMF) who underwent cord blood transplantation. Nine years after transplantation, she relapsed, which was confirmed by a bone marrow examination. We decided to treat her using azacitidine. After three courses of...
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| Published in | Internal Medicine Vol. 59; no. 21; pp. 2763 - 2767 |
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| Main Authors | , , , , , , , , , |
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The Japanese Society of Internal Medicine
01.11.2020
Japan Science and Technology Agency |
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| Abstract | We present the case of a 53-year-old woman with prefibrotic stage primary myelofibrosis (PMF) who underwent cord blood transplantation. Nine years after transplantation, she relapsed, which was confirmed by a bone marrow examination. We decided to treat her using azacitidine. After three courses of azacitidine, a partial cytogenetic response was confirmed. Azacitidine maintenance therapy successfully maintained a low level of recipient-origin peripheral blood cells with a stable hematological condition. Azacitidine may therefore be a promising therapeutic option for PMF patients who relapse after allogeneic stem cell transplantation. |
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| AbstractList | We present the case of a 53-year-old woman with prefibrotic stage primary myelofibrosis (PMF) who underwent cord blood transplantation. Nine years after transplantation, she relapsed, which was confirmed by a bone marrow examination. We decided to treat her using azacitidine. After three courses of azacitidine, a partial cytogenetic response was confirmed. Azacitidine maintenance therapy successfully maintained a low level of recipient-origin peripheral blood cells with a stable hematological condition. Azacitidine may therefore be a promising therapeutic option for PMF patients who relapse after allogeneic stem cell transplantation. We present the case of a 53-year-old woman with prefibrotic stage primary myelofibrosis (PMF) who underwent cord blood transplantation. Nine years after transplantation, she relapsed, which was confirmed by a bone marrow examination. We decided to treat her using azacitidine. After three courses of azacitidine, a partial cytogenetic response was confirmed. Azacitidine maintenance therapy successfully maintained a low level of recipient-origin peripheral blood cells with a stable hematological condition. Azacitidine may therefore be a promising therapeutic option for PMF patients who relapse after allogeneic stem cell transplantation.We present the case of a 53-year-old woman with prefibrotic stage primary myelofibrosis (PMF) who underwent cord blood transplantation. Nine years after transplantation, she relapsed, which was confirmed by a bone marrow examination. We decided to treat her using azacitidine. After three courses of azacitidine, a partial cytogenetic response was confirmed. Azacitidine maintenance therapy successfully maintained a low level of recipient-origin peripheral blood cells with a stable hematological condition. Azacitidine may therefore be a promising therapeutic option for PMF patients who relapse after allogeneic stem cell transplantation. |
| Author | Uematsu, Nozomu Ueki, Toshimitsu Kitahara, Mari Hiroshima, Yuki Shishido, Tsutomu Kobayashi, Hikaru Kazumoto, Hiroko Sato, Keijiro Sumi, Masahiko Kirihara, Takehiko |
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| Cites_doi | 10.1182/blood-2009-07-234880 10.1038/leu.2008.91 10.1016/j.leukres.2015.06.001 10.3324/haematol.2015.140996 10.1182/blood.V128.22.1948.1948 10.1007/s00277-019-03670-6 10.1016/j.bbmt.2017.03.034 10.1002/hon.2635 10.1182/blood-2011-09-377044 10.1016/j.bbmt.2009.10.025 10.1007/s00277-019-03766-z 10.1016/j.jcyt.2016.12.007 10.1007/s00277-020-03932-8 10.3324/haematol.2018.205211 |
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| Keywords | allogeneic stem cell transplantation primary myelofibrosis relapse azacitidine |
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| Notes | ObjectType-Case Study-2 SourceType-Scholarly Journals-1 content type line 14 ObjectType-Report-1 ObjectType-Feature-4 content type line 23 ObjectType-Article-3 Correspondence to Dr. Masahiko Sumi, sumin@nagano-med.jrc.or.jp |
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| References | 11. Janson D, Ayuk FA, Wolschke C, et al. Ruxolitinib for myelofibrosis patients relapsing after allogeneic hematopoietic transplantation [Abstract]. Blood 128: 1948, 2016. 9. Craddock C, Labopin M, Robin M, et al. Clinical activity of azacitidine in patients who relapse after allogeneic stem cell transplantation for acute myeloid leukemia. Haematologica 101: 879-883, 2016. 19. Martín I, Navarro B, Serrano A, et al. Impact of clinical features, cytogenetics, genetic mutations, and methylation dynamics of CDKN2B and DLC-1 promoters on treatment response to azacitidine. Ann Hematol 99: 527-537, 2020. 1. Thiele J, Barbui T, Kvasnicka HM, et al. Primary myelofibrosis. In: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Revised 4th ed. Swerdlow SH, Campo E, Harris NL, et al., Eds. IARC Press, Lyon, 2017: 44-50. 3. Kröger N, Holler E, Kobbe G, et al. Allogeneic stem cell transplantation after reduced-intensity conditioning in patients with myelofibrosis: a prospective, multicenter study of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Blood 114: 5264-5270, 2009. 2. Tefferi A. Primary myelofibrosis: 2017 update on diagnosis, risk-stratification, and management. Am J Hematol 91: 1262-1271, 2016. 13. Andriani A, Elli E, Trapè G, et al. Treatment of Philadelphia-negative myeloproliferative neoplasms in accelerated/blastic phase with azacitidine. Clinical results and identification of prognostic factors. Hematol Oncol 37: 291-295, 2019. 10. Woo J, Deeg HJ, Storer B, et al. Factors determining responses to azacitidine in patients with myelodysplastic syndromes and acute myeloid leukemia with early post-transplantation relapse: a prospective trial. Biol Blood Marrow Transplant 23: 176-179, 2017. 18. Alvarez-Larrán A, López-Guerra M, Rozman M, et al. Genomic characterization in triple-negative primary myelofibrosis and other myeloid neoplasms with bone marrow fibrosis. Ann Hematol 98: 2319-2328, 2019. 20. Kröger N, Panagiota V, Badbaran A, et al. Impact of molecular genetics on outcome in myelofibrosis patients after allogeneic stem cell transplantation. Biol Blood Marrow Transplant 23: 1095-1101, 2017. 6. McLornan DP, Szydlo R, Robin M, et al. Outcome of patients with Myelofibrosis relapsing after allogeneic stem cell transplant: a retrospective study by the Chronic Malignancies Working Party of EBMT. Br J Haematol 182: 418-422, 2018. 7. Schuler E, Boughoufala S, Rautenberg C, et al. Relapse patterns and treatment strategies in patients receiving allogeneic hematopoietic stem cell transplantation for myeloid malignancies. Ann Hematol 98: 1225-1235, 2019. 15. Goodyear OC, Dennis M, Jilani NY, et al. Azacitidine augments expansion of regulatory T cells after allogeneic stem cell transplantation in patients with acute myeloid leukemia (AML). Blood 119: 3361-3369, 2012. 4. Ballen KK, Shrestha S, Sobocinski KA, et al. Outcome of transplantation for myelofibrosis. Biol Blood Marrow Transplant 16: 358-367, 2010. 17. Tefferi A, Lasho TL, Finke CM, et al. CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia 28: 1472-1477, 2014. 8. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol 10: 223-232, 2009. 5. Robin M, de Wreede LC, Wolschke C, et al. Long-term outcome after allogeneic hematopoietic cell transplantation for myelofibrosis. Haematologica 104: 1782-1788, 2019. 14. Badar T, Kantarjian HM, Ravandi F, et al. Therapeutic benefit of decitabine, a hypomethylating agent, in patients with high-risk primary myelofibrosis and myeloproliferative neoplasm in accelerated or blastic/acute myeloid leukemia phase. Leuk Res 39: 950-956, 2015. 12. Quintás-Cardama A, Tong W, Kantarjian H, et al. A phase II study of 5-azacitidine for patients with primary and post-essential thrombocythemia/polycythemia vera myelofibrosis. Leukemia 22: 965-970, 2008. 16. Ishikawa T, Fujii N, Imada M, et al. Graft-versus-leukemia effect with a WT1-specific T-cell response induced by azacitidine and donor lymphocyte infusions after allogeneic hematopoietic stem cell transplantation. Cytotherapy 19: 514-520, 2017. 11 12 13 14 15 16 17 18 19 1 2 3 4 5 6 7 8 9 20 10 |
| References_xml | – reference: 9. Craddock C, Labopin M, Robin M, et al. Clinical activity of azacitidine in patients who relapse after allogeneic stem cell transplantation for acute myeloid leukemia. Haematologica 101: 879-883, 2016. – reference: 18. Alvarez-Larrán A, López-Guerra M, Rozman M, et al. Genomic characterization in triple-negative primary myelofibrosis and other myeloid neoplasms with bone marrow fibrosis. Ann Hematol 98: 2319-2328, 2019. – reference: 10. Woo J, Deeg HJ, Storer B, et al. Factors determining responses to azacitidine in patients with myelodysplastic syndromes and acute myeloid leukemia with early post-transplantation relapse: a prospective trial. Biol Blood Marrow Transplant 23: 176-179, 2017. – reference: 7. Schuler E, Boughoufala S, Rautenberg C, et al. Relapse patterns and treatment strategies in patients receiving allogeneic hematopoietic stem cell transplantation for myeloid malignancies. Ann Hematol 98: 1225-1235, 2019. – reference: 15. Goodyear OC, Dennis M, Jilani NY, et al. Azacitidine augments expansion of regulatory T cells after allogeneic stem cell transplantation in patients with acute myeloid leukemia (AML). Blood 119: 3361-3369, 2012. – reference: 12. Quintás-Cardama A, Tong W, Kantarjian H, et al. A phase II study of 5-azacitidine for patients with primary and post-essential thrombocythemia/polycythemia vera myelofibrosis. Leukemia 22: 965-970, 2008. – reference: 1. Thiele J, Barbui T, Kvasnicka HM, et al. Primary myelofibrosis. In: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Revised 4th ed. Swerdlow SH, Campo E, Harris NL, et al., Eds. IARC Press, Lyon, 2017: 44-50. – reference: 8. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol 10: 223-232, 2009. – reference: 14. Badar T, Kantarjian HM, Ravandi F, et al. Therapeutic benefit of decitabine, a hypomethylating agent, in patients with high-risk primary myelofibrosis and myeloproliferative neoplasm in accelerated or blastic/acute myeloid leukemia phase. Leuk Res 39: 950-956, 2015. – reference: 11. Janson D, Ayuk FA, Wolschke C, et al. Ruxolitinib for myelofibrosis patients relapsing after allogeneic hematopoietic transplantation [Abstract]. Blood 128: 1948, 2016. – reference: 17. Tefferi A, Lasho TL, Finke CM, et al. CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia 28: 1472-1477, 2014. – reference: 5. Robin M, de Wreede LC, Wolschke C, et al. Long-term outcome after allogeneic hematopoietic cell transplantation for myelofibrosis. Haematologica 104: 1782-1788, 2019. – reference: 16. Ishikawa T, Fujii N, Imada M, et al. Graft-versus-leukemia effect with a WT1-specific T-cell response induced by azacitidine and donor lymphocyte infusions after allogeneic hematopoietic stem cell transplantation. Cytotherapy 19: 514-520, 2017. – reference: 2. Tefferi A. Primary myelofibrosis: 2017 update on diagnosis, risk-stratification, and management. Am J Hematol 91: 1262-1271, 2016. – reference: 19. Martín I, Navarro B, Serrano A, et al. Impact of clinical features, cytogenetics, genetic mutations, and methylation dynamics of CDKN2B and DLC-1 promoters on treatment response to azacitidine. Ann Hematol 99: 527-537, 2020. – reference: 13. Andriani A, Elli E, Trapè G, et al. Treatment of Philadelphia-negative myeloproliferative neoplasms in accelerated/blastic phase with azacitidine. Clinical results and identification of prognostic factors. Hematol Oncol 37: 291-295, 2019. – reference: 3. Kröger N, Holler E, Kobbe G, et al. Allogeneic stem cell transplantation after reduced-intensity conditioning in patients with myelofibrosis: a prospective, multicenter study of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Blood 114: 5264-5270, 2009. – reference: 4. Ballen KK, Shrestha S, Sobocinski KA, et al. Outcome of transplantation for myelofibrosis. Biol Blood Marrow Transplant 16: 358-367, 2010. – reference: 6. McLornan DP, Szydlo R, Robin M, et al. Outcome of patients with Myelofibrosis relapsing after allogeneic stem cell transplant: a retrospective study by the Chronic Malignancies Working Party of EBMT. Br J Haematol 182: 418-422, 2018. – reference: 20. Kröger N, Panagiota V, Badbaran A, et al. Impact of molecular genetics on outcome in myelofibrosis patients after allogeneic stem cell transplantation. Biol Blood Marrow Transplant 23: 1095-1101, 2017. – ident: 2 – ident: 17 – ident: 3 doi: 10.1182/blood-2009-07-234880 – ident: 12 doi: 10.1038/leu.2008.91 – ident: 1 – ident: 14 doi: 10.1016/j.leukres.2015.06.001 – ident: 9 doi: 10.3324/haematol.2015.140996 – ident: 11 doi: 10.1182/blood.V128.22.1948.1948 – ident: 10 – ident: 7 doi: 10.1007/s00277-019-03670-6 – ident: 20 doi: 10.1016/j.bbmt.2017.03.034 – ident: 13 doi: 10.1002/hon.2635 – ident: 15 doi: 10.1182/blood-2011-09-377044 – ident: 4 doi: 10.1016/j.bbmt.2009.10.025 – ident: 18 doi: 10.1007/s00277-019-03766-z – ident: 6 – ident: 8 – ident: 16 doi: 10.1016/j.jcyt.2016.12.007 – ident: 19 doi: 10.1007/s00277-020-03932-8 – ident: 5 doi: 10.3324/haematol.2018.205211 |
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| Snippet | We present the case of a 53-year-old woman with prefibrotic stage primary myelofibrosis (PMF) who underwent cord blood transplantation. Nine years after... |
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| SubjectTerms | allogeneic stem cell transplantation Antimetabolites, Antineoplastic - therapeutic use azacitidine Azacitidine - therapeutic use Blood cells Bone marrow transplantation Case Report Cord blood Cord Blood Stem Cell Transplantation - adverse effects Cytogenetics Female Hematopoietic Stem Cell Transplantation - adverse effects Humans Internal medicine Middle Aged Myelofibrosis Peripheral blood primary myelofibrosis Primary Myelofibrosis - drug therapy Recurrence relapse Salvage Therapy - methods Stem cell transplantation Transplantation, Homologous Treatment Outcome |
| Title | Salvage Therapy Using Azacitidine for Relapsed Primary Myelofibrosis after Cord Blood Transplantation |
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