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 multice

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• 作者：Hui Liu (1)
  Xiao Zhai (1)
  Zhaoyang Song (2)
  Jing Sun (1)
  Yang Xiao (3)
  Danian Nie (4)
  Yu Zhang (1)
  Fen Huang (1)
  Hongsheng Zhou (1)
  Zhiping Fan (1)
  Sanfang Tu (2)
  Yonghua Li (3)
  Xutao Guo (1)
  Guopan Yu (1)
  Qifa Liu (1)
  
• 关键词：Busulfan ; Fludarabine ; Allogeneic hematopoietic stem cell transplantation
• 刊名：Journal of Hematology & Oncology
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：6
• 期：1
• 全文大小：269KB
• 参考文献：1. De Lima M, Anagnostopoulos A, Munsell M, Shahjahan M, Ueno N, Ippoliti C, Andersson BS, Gajewski J, Couriel D, Cortes J, Donato M, Neumann J, Champlin R, Giralt S: Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation. / Blood 2004,104(3):865-72. CrossRef
  2. Copelan EA: Hematopoietic stem-cell transplantation. / N Engl J Med 2006,354(17):1813-826. CrossRef
  3. Ali N, Adil SN, Shaikh MU, Moosajee M, Masood N: Outcome of match related allogeneic stem cell transplantation procedures performed from 2004 till 2011. / Exp Hematol Oncol 2012,1(1):13. CrossRef
  4. Ciurea SO, Andersson BS: Busulfan in hematopoietic stem cell transplantation. / Biol Blood Marrow Tr 2009,15(5):523-36. CrossRef
  5. Russell JA, Tran HT, Quinlan D, Chaudhry A, Duggan P, Brown C, Stewart D, Ruether JD, Morris D, Glick S, Gyonyor E, Andersson BS: Once-daily intravenous busulfan given with fludarabine as conditioning for allogeneic stem cell transplantation: study of pharmacokinetics and early clinical outcomes. / Biol Blood Marrow Tr 2002,8(9):468-76. CrossRef
  6. De Lima M, Couriel D, Thall PF, Wang X, Madden T, Jones R, Shpall EJ, Shahjahan M, Pierre B, Giralt S, Korbling M, Russell JA, Champlin RE, Andersson BS: 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. CrossRef
  7. Iravani M, Evazi MR, Mousavi SA, Shamshiri AR, Tavakoli M, Ashouri A, Samiee S, Chahardovali B, Alimoghaddam K, Ghaffari SH, Ghavamzadeh A: Fludarabine and busulfan as a myeloablative conditioning regimen for allogeneic stem cell transplantation in high- and standard-risk leukemic patients. / Biol Blood Marrow Tr 2007,40(2):105-10.
  8. Andersson BS, De Lima M, Thall PF, Wang X, Couriel D, Korbling M, Roberson S, Giralt S, Pierre B, Russell JA, Shpall EJ, Jones RB, Champlin RE: 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 Tr 2008,14(6):672-84. CrossRef
  9. Chae YS, Sohn SK, Kim JG, Cho YY, Moon JH, Shin HJ, Chung JS, Cho GJ, Yang DH, Lee JJ, Kim YK, Kim HJ: New myeloablative conditioning regimen with fludarabine and busulfan for allogeneic stem cell transplantation: comparison with BuCy2. / Bone Marrow Transplant 2007,40(6):541-47. CrossRef
  10. Lee JH, Choi J, Kwon KA, Lee S, Oh SY, Kwon HC, Kim HJ, Han JY, Kim SH: Fludarabine-based myeloablative regimen as pretransplant conditioning therapy in adult acute leukemia/myelodysplastic syndrome: comparison with oral or intravenous busulfan with cyclophosphamide. / Korean J Hematol 2010,45(2):102-08. CrossRef
  11. Chunduri S, Dobogai LC, Peace D, Saunthararajah Y, Quigley J, Chen YH, Mahmud N, Hurter E, Beri R, Rondelli D: Fludarabine/i.v. BU conditioning regimen: myeloablative, reduced intensity or both? / BMT 2008,41(11):935-40.
  12. Pidala J, Kim J, Anasetti C, Kharfan-Dabaja MA, Nishihori T, Field T, Perkins J, Perez L, Fernandez HF: Pharmacokinetic targeting of intravenous busulfan reduces conditioning regimen related toxicity following allogeneic hematopoietic cell transplantation for acute myelogenous leukemia. / J Hematol Oncol 2010,3(1):36. CrossRef
  13. Shimoni A, Hardan I, Shem-Tov N, Yeshurun M, Yerushalmi R, Avigdor A, Ben-Bassat I, Nagler A: Allogeneic hematopoietic stem-cell transplantation in AML and MDS using myeloablative versus reduced-intensity conditioning: the role of dose intensity. / Leukemia 2006,20(2):322-28. CrossRef
  14. Lee JH, Joo YD, Kim H, Ryoo HM, Kim MK, Lee GW, Lee JH, Lee WS, Park JH, Bae SH, Hyun MS, Kim DY, Kim SD, Min YJ, Lee KH: Randomized Trial of Myeloablative Conditioning Regimens: Busulfan Plus Cyclophosphamide Versus Busulfan Plus Fludarabine. / J Clin Oncol 2012. in press
  15. Shimoni A, Hardan I, Shem-Tov N, Yerushalmi R, Nagler A: Allogeneic hematopoietic stem-cell transplantation in AML and MDS using myeloablative versus reduced-intensity conditioning: long-term follow-up. / Leukemia 2010,24(5):1050-052. CrossRef
  16. Liu QF, Fan ZP, Zhang Y, Jiang ZJ, Wang CY, Xu D, Sun J, Xiao Y, Tan H: Sequential intensified conditioning and tapering of prophylactic immunosuppressants for graft-versus-host disease in allogeneic hematopoietic stem cell transplantation for refractory leukemia. / BBMT 2009,15(11):1376-385.
  17. Xuan L, Huang F, Fan Z, Zhou H, Zhang X, Yu G, Zhang Y, Liu C, Sun J, Liu Q: Effects of intensified conditioning on Epstein-Barr virus and cytomegalovirus infections in allogeneic hematopoietic stem cell transplantation for hematological malignancies. / J Hematol Oncol 2012, 5:46. CrossRef
  18. Bearman SI, Appelbaum FR, Buckner CD, Petersen FB, Fisher LD, Clift RA, Thomas ED: Regimen-related toxicity in patients undergoing bone marrow transplantation. / J Clin Oncol 1988,6(10):1562-568.
  19. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED: Consensus Conference on Acute GVHD Grading. / Bone Marrow Transplant 1994,15(6):825-28.
  20. Horwitz ME, Sullivan KM: Chronic graft-versus-host disease. / Blood Rev 2006,20(1):15-7. CrossRef
  21. O’Donnell MR, Abboud CN, Altman J, Appelbaum FR, Arber DA, Attar E, Borate U, Coutre SE, Damon LE, Goorha S, Lancet J, Maness LJ, Marcucci G, Millenson MM, Moore JO, Ravandi F, Shami PJ, Smith BD, Stone RM, Strickland SA, Tallman MS, Wang ES, Naganuma M, Gregory KM: Acute myeloid leukemia. / J Natl Compr Canc Netw 2012,10(8):984-021.
  22. McDonald GB, Slattery JT, Bouvier ME, Ren S, Batchelder AL, Kalhorn TF, Schoch HG, Anasetti C, Gooley T: Cyclophosphamide metabolism, liver toxicity, and mortality following hematopoietic stem cell transplantation. / Blood 2003,101(5):2043-048. CrossRef
  23. Ozcan M, Ustün C, Ak?a?layan E, Akan H, Arslan O, Ilhan O, Beksa? M, Gürman G, Demirer T, Arat M, Celebi H, Konuk N, Uysal A, Ko? H: Recombinant human granulocyte colony-stimulating factor (rh-G-CSF) may accelerate hematopoietic recovery after HLA-identical sibling allogeneic peripheral blood stem cell transplantation. / BMT 2001,27(5):499-05.
  24. Anderson D, DeFor T, Burns L, McGlave P, Miller J, Wagner J, Weisdorf D: A comparison of related donor peripheral blood and bone marrow transplants: importance of late-onset chronic graft-versus-host disease and infections. / BBMT 2003,9(1):52-9.
  25. Lazzarino M, Orlandi E, Baldanti F, Furione M, Pagnucco G, Astori C, Arcaini L, Viglio A, Paulli M, Gerna G, Bernasconi C: The immunosuppression and potential for EBV reactivation of fludarabine combined with cyclophosphamide and dexamethasone in patients with lymphoproliferative disorders. / Br J Haematol 1999,107(4):877-82. CrossRef
  26. Bainton RD, Byrne JL, Davy BJ, Russell NH: CMV infection following nonmyeloablative allogeneic stem cell transplantation using Campath. / Blood 2002,100(10):3843-844. CrossRef
  27. Pidala J: Graft-vs-host disease following allogeneic hematopoietic cell transplantation. / Cancer Control 2011,18(4):268-76.
  28. Reddy P, Socie G, Cutler C, Weisdorf D: GVHD prevention: an ounce is better than a pound. / BBMT 2012,18(1 Suppl):S17-6.
  29. Jing Y, Li H, Zhao Y, Bo J, Wang S, Wang Q, Huang W, Gao C, Yu L: Efficacy of allogeneic and autologous hematopoietic SCT in patients with AML after first complete remission. / BMT 2012. in press
  30. Wang Y, Liu DH, Liu KY, Xu LP, Zhang XH, Han W, Chen H, Chen YH, Huang XJ: Impact of Pretransplantation Risk Factors on Post Transplantation Outcome of Patients With Acute Myeloid Leukemia in Remission After Haploidentical Hematopoietic Stem Cell Transplantation. / BBMT 2012. in press
  
• 作者单位：Hui Liu (1)
  Xiao Zhai (1)
  Zhaoyang Song (2)
  Jing Sun (1)
  Yang Xiao (3)
  Danian Nie (4)
  Yu Zhang (1)
  Fen Huang (1)
  Hongsheng Zhou (1)
  Zhiping Fan (1)
  Sanfang Tu (2)
  Yonghua Li (3)
  Xutao Guo (1)
  Guopan Yu (1)
  Qifa Liu (1)
  
  1. Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
  2. Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China
  3. Department of Hematology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China
  4. Department of Hematology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
  
• ISSN：1756-8722

文摘

Objective We conducted a prospective, randomized, open-label, multicenter study to compare busulfan plus fludarabine (BuFlu) with busulfan plus cyclophosphamide (BuCy) as the conditioning regimen in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia (AML) in first complete remission (CR1). Methods Totally 108 AML-CR1 patients undergoing allo-HSCT were randomized into BuCy (busulfan 1.6 mg/kg, q12 hours, -7?~-4d; cyclophosphamide 60 mg/kg.d, -3?~-2d) or BuFlu (busulfan 1.6 mg/kg, q12 hours, -5?~-2d; fludarabine 30 mg/m2.d, -6?~-2d) group. Hematopoietic engraftment, regimen-related toxicity (RRT), graft-versus-host disease (GVHD), transplant related mortality (TRM), and overall survival were compared between the two groups. Results All patients achieved hematopoietic reconstitution except for two patients who died of RRT during conditioning. All patients obtained complete donor chimerism by day +30 post-transplantation. The incidence of total and III-IV RRT were 94.4% and 81.5% (P--.038), and 16.7% and 0.0% (P--.002), respectively, in BuCy and BuFlu group. With a median follow up of 609 (range, 3-130) days after transplantation, the 5-year cumulative incidence of TRM were 18.8?±-.9% and 9.9?±-.3% (P--.104); the 5-year cumulative incidence of leukemia relapse were 16.5?±-.8% and 16.2?±-.3% (P--.943); the 5-year disease-free survival and overall survival were 67.4?±-.6% and 75.3?±-.2% (P = 0.315), and 72.3?±-.5% and 81.9?±-.0% (P--.177), respectively in BuCy and BuFlu group. Conclusion Compared with BuCy, BuFlu as a myeloablative condition regimen was associated with lower toxicities and comparable anti-leukemic activity in AML-CR1 patients undergoing allo-HSCT.