Evaluate the Efficacy of Myeloablative Conditioning Regimens for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myelogenous Leukemia at BTH, Vietnam
-
Thu Hanh Nguyen
,
Huu Than Huynh
,
Hung Quang Tran
,
Quang The Nguyen
,
Phu Duc Vinh Huynh
,
Nam Duy Hoang
,
Tuan Xuan Ma
,
Duong Thi Thuy Do
,
Dung Chi Phu
,
Man Van Huynh
Abstract
Background: Busulfan plus cyclophosphamide (Bu/Cy) is considered one of the classical myeloablative conditioning regimens. However, its toxicity can significantly increase mortality rates. To reduce both acute and long-term complications after hematopoietic stem cell transplantation (HSCT), newer conditioning regimens are being investigated. The purposes of this study were to assess the efficacy and safety of busulfan plus cyclophosphamide (Bu/Cy) and busulfan plus fludarabine (Bu/Flu) conditioning regimen for allogeneic HSCT (allo-HSCT) in acute myelogenous leukemia (AML).
Materials and Methods: We conducted a single-center, retrospective analysis of AML, both adults and children, who underwent either Bu/Cy or Bu/Flu conditioning regimen for allo-HSCT and received peripheral blood stem cell transplants from HLA-matched donors.
Results: From 2005 – 2019, 49 AML patients receiving Bu/Cy and 21 receiving Bu/Flu were identified, meeting inclusion criteria. The two groups showed no significant differences in age, gender, disease status pre-transplant, the median time to neutrophil and platelet engraftment. Bu/Flu patients had a shorter duration of neutropenia (median 7 days vs 10 days, p = 0.001) and shorter duration of thrombocytopenia (median 10 days vs 15 days, p = 0.016) than Bu/Cy. No difference was observed in disease-free survival (DFS) and overall survival (OS) between the two groups. Both univariate and multivariate analyses showed that age, disease status pre-transplant, and chronic graft-versus-host disease (GvHD) are related to worse DFS and OS.
Conclusion: With similar efficacy to Bu/Cy but faster neutrophil and platelet recovery time, Bu/Flu is suitable as a pre-HSCT conditioning regimen for patients with AML.
1. Visani G, Malagola M, Guiducci B, et al. Conditioning regimens in acute myeloid leukemia. Expert Rev Hematol.2014; 7 (4):465-79.
2. Burnett AK, Knapper S, Treleaven J, Barrett AJ (eds). Hematopoietic stem cell transplantation in clinical practice. Elsevier: London, UK, 2009.
3. Ganapule A, Nemani S, Korula A, et al. Allogeneic Stem Cell Transplant for Acute Myeloid Leukemia: Evolution of an Effective Strategy in India. J Glob Oncol. 2017; 3 (6):773-781.
4. Gupta V, Tallman MS, Weisdorf DJ. Allogeneic hematopoietic cell transplantation for adults with acute myeloid leukemia: myths, controversies, and unknowns. Blood. 117 (8):2307- 18.
5. Hamilton BK, Copelan EA. Concise review: the role of hematopoietic stem cell transplantation in the treatment of acute myeloid leukemia. Stem Cells. 2012; 30 (8):1581-6.
6. Cornelissen JJ, Gratwohl A, Schlenk RF, et al. The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach. Nat Rev Clin Oncol. 2012; 9 (10):579-90.
7. Kanate AS, Pasquini MC, Hari PN, et al. Allogeneic hematopoietic cell transplant for acute myeloid leukemia: Current state in 2013 and future directions. World J Stem Cells. 2014; 6 (2):69-81.
8. Vyas P, Appelbaum FR, Craddock C. Allogeneic hematopoietic cell transplantation for acute myeloid leukemia. Biol Blood Marrow Transplant. 2015; 21 (1):8-15.
9. Giralt S, Estey E, Albitar M, et al. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft- versus-leukemia without myeloablative therapy. Blood. 1997; 89 (12):4531-6.
10. de Lima M, Couriel D, Thall PF, et al. Once-daily intravenous busulfan and fludarabine: clinical and pharmacokinetic results of a myeloablative, reduced- toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDS. Blood. 2004; 104 (3):857-64.
11. Andersson BS, de Lima M, Thall PF, et al. Once daily i.v. busulfan and fludarabine (i.v. Bu-Flu) compares favorably with i.v. busulfan and cyclophosphamide (i.v. BuCy2) as pretransplant conditioning therapy in AML/MDS. Biol Blood Marrow Transplant. 2008; 14 (6):672-84.
12. Almog S, Kurnik D, Shimoni A, et al. Linearity and stability of intravenous busulfan pharmacokinetics and the role of glutathione in busulfan elimination. Biol Blood Marrow Transplant. 2011; 17 (1):117-23.
13. Raida L, Tucek P, Faber E, et al. Comparison of new flu-bu12-tg conditioning with the standard bu-cy myeloablative regimen in patients undergoing allogeneic stem cell transplantation for acute myeloid leukemia. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2011; 155 (4):327-32.
14. Fedele R, Messina G, Martinello T, et al. Tolerability and efficacy of busulfan and fludarabine as allogeneic pretransplant conditioning therapy in acute myeloid leukemia: comparison with busulfan and cyclophosphamide regimen. Clin Lymphoma Myeloma Leuk. 2014; 14 (6):493-500.
15. Liu H, Zhai X, Song Z, et al. Busulfan plus fludarabine as a myeloablative conditioning regimen compared with busulfan plus cyclophosphamide for acute myeloid leukemia in first complete remission undergoing allogeneic hematopoietic stem cell transplantation: a prospective and multicenter study. J Hematol Oncol. 2013; 6:15.
16. Patel SS, Rybicki L, Emrick A, et al. Comparative Effectiveness of Busulfan/Cyclophosphamide Versus Busulfan/Fludarabine Myeloablative Conditioning for Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia. Blood. 2018; 132 (Supplement 1):3365.
17. Rambaldi A, Grassi A, Masciulli A, et al. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015; 16 (15):1525-1536.
18. Eapen M, Brazauskas R, Hemmer M, et al. Hematopoietic cell transplant for acute myeloid leukemia and myelodysplastic syndrome: conditioning regimen intensity. Blood Adv. 2018; 2 (16):2095-2103.
19. Lee JH, Joo YD, Kim H, et al. Randomized trial of myeloablative conditioning regimens: busulfan plus cyclophosphamide versus busulfan plus fludarabine. J Clin Oncol. 2013; 31 (6):701-709.
20. Harris AC, Boelens JJ, Woo Ahn K, et al. Comparison of Outcomes for Myeloablative Conditioning Regimens Combining Busulfan with Either Cyclophosphamide or Fludarabine in Children. Blood. 2018; 128 (22):664.
21. Kantarjian H, O'Brien S, Cortes J, et al. Results of intensive chemotherapy in 998 patients age 65 years or older with acute myeloid leukemia or high-risk myelodysplastic syndrome: predictive prognostic models for outcome. Cancer 106 (5):1090-1098.
22. Baron F, Labopin M, Peniket A, et al. Reduced-intensity conditioning with fludarabine and busulfan versus fludarabin and melphalan for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Cancer. 2015; 121 (7):1048-55.
23. Blaise D, Tabrizi R, Boher JM, et al. Randomized study of 2 reduced-intensity conditioning strategies for human leukocyte antigen-matched, related allogeneic peripheral blood stem cell transplantation: prospective clinical and socioeconomic evaluation. Cancer. 2013; 119 (3):602- 11.
24. Magenau JM, Braun T, Reddy P, et al. Allogeneic transplantation with myeloablative FluBu4 conditioning improves survival compared to reduced intensity FluBu2 conditioning for acute myeloid leukemia in remission. Ann Hematol. 2015; 94 (6):1033-1041
25. Bornhauser M, Storer B, Slattery JT, et al. Conditioning with fludarabine and targeted busulfan for transplantation of allogeneic hematopoietic stem cells. Blood. 2003; 102 (3):820-6.
26. Madden T, de Lima M, Thapar N, et al. Pharmacokinetics of once-daily IV busulfan as part of pretransplantation preparative regimens: a comparison with an every 6-hour dosing schedule. Biol Blood Marrow Transplant. 2017; 13 (1):56-64.
27. Kako S, Fujiwara S, Sato M, et al. Safety and Efficacy of Once-Daily Intravenous Busulfan in Allogeneic Transplantation: A Matched-Pair Analysis. 2018; Biol Blood Marrow Transplant. 24 (10):2139-2144.
28. Andersson BS, Thall PF, Valdez BC, et al. Fludarabine with pharmacokinetically guided IV busulfan is superior to fixed-dose delivery in pretransplant conditioning of AML/MDS patients. Bone Marrow Transplant. 2017; 52 (4):580-587.
2. Burnett AK, Knapper S, Treleaven J, Barrett AJ (eds). Hematopoietic stem cell transplantation in clinical practice. Elsevier: London, UK, 2009.
3. Ganapule A, Nemani S, Korula A, et al. Allogeneic Stem Cell Transplant for Acute Myeloid Leukemia: Evolution of an Effective Strategy in India. J Glob Oncol. 2017; 3 (6):773-781.
4. Gupta V, Tallman MS, Weisdorf DJ. Allogeneic hematopoietic cell transplantation for adults with acute myeloid leukemia: myths, controversies, and unknowns. Blood. 117 (8):2307- 18.
5. Hamilton BK, Copelan EA. Concise review: the role of hematopoietic stem cell transplantation in the treatment of acute myeloid leukemia. Stem Cells. 2012; 30 (8):1581-6.
6. Cornelissen JJ, Gratwohl A, Schlenk RF, et al. The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach. Nat Rev Clin Oncol. 2012; 9 (10):579-90.
7. Kanate AS, Pasquini MC, Hari PN, et al. Allogeneic hematopoietic cell transplant for acute myeloid leukemia: Current state in 2013 and future directions. World J Stem Cells. 2014; 6 (2):69-81.
8. Vyas P, Appelbaum FR, Craddock C. Allogeneic hematopoietic cell transplantation for acute myeloid leukemia. Biol Blood Marrow Transplant. 2015; 21 (1):8-15.
9. Giralt S, Estey E, Albitar M, et al. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft- versus-leukemia without myeloablative therapy. Blood. 1997; 89 (12):4531-6.
10. de Lima M, Couriel D, Thall PF, et al. Once-daily intravenous busulfan and fludarabine: clinical and pharmacokinetic results of a myeloablative, reduced- toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDS. Blood. 2004; 104 (3):857-64.
11. Andersson BS, de Lima M, Thall PF, et al. Once daily i.v. busulfan and fludarabine (i.v. Bu-Flu) compares favorably with i.v. busulfan and cyclophosphamide (i.v. BuCy2) as pretransplant conditioning therapy in AML/MDS. Biol Blood Marrow Transplant. 2008; 14 (6):672-84.
12. Almog S, Kurnik D, Shimoni A, et al. Linearity and stability of intravenous busulfan pharmacokinetics and the role of glutathione in busulfan elimination. Biol Blood Marrow Transplant. 2011; 17 (1):117-23.
13. Raida L, Tucek P, Faber E, et al. Comparison of new flu-bu12-tg conditioning with the standard bu-cy myeloablative regimen in patients undergoing allogeneic stem cell transplantation for acute myeloid leukemia. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2011; 155 (4):327-32.
14. Fedele R, Messina G, Martinello T, et al. Tolerability and efficacy of busulfan and fludarabine as allogeneic pretransplant conditioning therapy in acute myeloid leukemia: comparison with busulfan and cyclophosphamide regimen. Clin Lymphoma Myeloma Leuk. 2014; 14 (6):493-500.
15. Liu H, Zhai X, Song Z, et al. Busulfan plus fludarabine as a myeloablative conditioning regimen compared with busulfan plus cyclophosphamide for acute myeloid leukemia in first complete remission undergoing allogeneic hematopoietic stem cell transplantation: a prospective and multicenter study. J Hematol Oncol. 2013; 6:15.
16. Patel SS, Rybicki L, Emrick A, et al. Comparative Effectiveness of Busulfan/Cyclophosphamide Versus Busulfan/Fludarabine Myeloablative Conditioning for Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia. Blood. 2018; 132 (Supplement 1):3365.
17. Rambaldi A, Grassi A, Masciulli A, et al. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015; 16 (15):1525-1536.
18. Eapen M, Brazauskas R, Hemmer M, et al. Hematopoietic cell transplant for acute myeloid leukemia and myelodysplastic syndrome: conditioning regimen intensity. Blood Adv. 2018; 2 (16):2095-2103.
19. Lee JH, Joo YD, Kim H, et al. Randomized trial of myeloablative conditioning regimens: busulfan plus cyclophosphamide versus busulfan plus fludarabine. J Clin Oncol. 2013; 31 (6):701-709.
20. Harris AC, Boelens JJ, Woo Ahn K, et al. Comparison of Outcomes for Myeloablative Conditioning Regimens Combining Busulfan with Either Cyclophosphamide or Fludarabine in Children. Blood. 2018; 128 (22):664.
21. Kantarjian H, O'Brien S, Cortes J, et al. Results of intensive chemotherapy in 998 patients age 65 years or older with acute myeloid leukemia or high-risk myelodysplastic syndrome: predictive prognostic models for outcome. Cancer 106 (5):1090-1098.
22. Baron F, Labopin M, Peniket A, et al. Reduced-intensity conditioning with fludarabine and busulfan versus fludarabin and melphalan for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Cancer. 2015; 121 (7):1048-55.
23. Blaise D, Tabrizi R, Boher JM, et al. Randomized study of 2 reduced-intensity conditioning strategies for human leukocyte antigen-matched, related allogeneic peripheral blood stem cell transplantation: prospective clinical and socioeconomic evaluation. Cancer. 2013; 119 (3):602- 11.
24. Magenau JM, Braun T, Reddy P, et al. Allogeneic transplantation with myeloablative FluBu4 conditioning improves survival compared to reduced intensity FluBu2 conditioning for acute myeloid leukemia in remission. Ann Hematol. 2015; 94 (6):1033-1041
25. Bornhauser M, Storer B, Slattery JT, et al. Conditioning with fludarabine and targeted busulfan for transplantation of allogeneic hematopoietic stem cells. Blood. 2003; 102 (3):820-6.
26. Madden T, de Lima M, Thapar N, et al. Pharmacokinetics of once-daily IV busulfan as part of pretransplantation preparative regimens: a comparison with an every 6-hour dosing schedule. Biol Blood Marrow Transplant. 2017; 13 (1):56-64.
27. Kako S, Fujiwara S, Sato M, et al. Safety and Efficacy of Once-Daily Intravenous Busulfan in Allogeneic Transplantation: A Matched-Pair Analysis. 2018; Biol Blood Marrow Transplant. 24 (10):2139-2144.
28. Andersson BS, Thall PF, Valdez BC, et al. Fludarabine with pharmacokinetically guided IV busulfan is superior to fixed-dose delivery in pretransplant conditioning of AML/MDS patients. Bone Marrow Transplant. 2017; 52 (4):580-587.
| Files | ||
| Issue | Vol 18 No 3 (2024) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijhoscr.v18i3.16106 | |
| Keywords | ||
| Allo-HSCT Conditioning regimen AML Vietnam | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Nguyen T, Huynh HT, Tran H, Nguyen Q, Huynh P, Hoang N, Ma T, Do D, Phu D, Huynh M. Evaluate the Efficacy of Myeloablative Conditioning Regimens for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myelogenous Leukemia at BTH, Vietnam. Int J Hematol Oncol Stem Cell Res. 2024;18(3):254-261.
