Pharmacology of dimethanesulfonate alkylating agents: Busulfan and treosulfan

Expert Opinion on Drug Metabolism and Toxicology

Volumn 9, Issue 3, 2013, Pages 333-347

  Galaup, Ariane ^a   Paci, Angelo ^b  

^a PSL RESEARCH UNIVERSITY   (France)

^b INSTITUT GUSTAVE ROUSSY   (France)

Author keywords

Busulfan; Dimethanesulfonate alkylating agents; Hematopoietic stem cell transplantation; Pharmacodynamics; Pharmacokinetics; Therapeutic drug monitoring; Treosulfan

Indexed keywords

ACID; BUSULFAN; CYCLOPHOSPHAMIDE; DEFIBROTIDE; DNA; GLUTATHIONE TRANSFERASE; HEPARIN; TREOSULFAN;

ACUTE GRANULOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC LEUKEMIA; ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; ANEMIA; ANTINEOPLASTIC ACTIVITY; BLOOD TOXICITY; BONE MARROW DEPRESSION; BONE MARROW SUPPRESSION; CANCER COMBINATION CHEMOTHERAPY; CANCER SURVIVAL; CHRONIC MYELOID LEUKEMIA; CONCENTRATION RESPONSE; CYTOTOXICITY; DETOXIFICATION; DIARRHEA; DNA STRAND BREAKAGE; DOSE RESPONSE; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG HALF LIFE; DRUG MECHANISM; DRUG METABOLISM; DRUG STRUCTURE; ENGRAFTMENT; G2 PHASE CELL CYCLE CHECKPOINT; GLUTATHIONE METABOLISM; HEMATOPOIETIC STEM CELL; HUMAN; LEUKEMIA CELL; LEUKOPENIA; LIVER CELL; LIVER TOXICITY; MAXIMUM TOLERATED DOSE; MITOSIS INHIBITION; MUCOSA INFLAMMATION; MYELODYSPLASTIC SYNDROME; NONHUMAN; PH; PHASE 1 CLINICAL TRIAL (TOPIC); PRURITUS; RASH; RECURRENCE FREE SURVIVAL; REVIEW; SINGLE DRUG DOSE; STOMATITIS; THROMBOCYTOPENIA; TREATMENT DURATION;

ADMINISTRATION, ORAL; ANIMALS; ANTINEOPLASTIC AGENTS, ALKYLATING; BUSULFAN; CYCLOPHOSPHAMIDE; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HEMATOLOGIC NEOPLASMS; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMANS; LIVER; MYELOABLATIVE AGONISTS; OVARIAN NEOPLASMS; VIDARABINE; WHOLE-BODY IRRADIATION;

EID: 84874056467     PISSN: 17425255     EISSN: 17447607     Source Type: Journal    
DOI: 10.1517/17425255.2013.737319     Document Type: Review

References (126)

1. Crawford SW, Longton G, Storb R. Acute graft-versus-host disease and the risks for idiopathic pneumonia after marrow transplantation for severe aplastic anemia. BMT 1993;12(3):225-31 (Pubitemid 23268157)
2. Buggia I, Locatelli F, Regazzi MB, Zecca M. Busulfan. Ann Pharmacother 1994;Sep28(9):1055-62 (Pubitemid 24292697)
3. Slattery JT, Risler LJ. Therapeutic drug monitoring of busulfan in haematologic stem cell transplantation. Ther Drug Monit 1998;20(5):543-9 (Pubitemid 28463447)
4. Beelen DW, Trenschel R, Casper J, et al. Dose-escalated treosulphan in combination with cyclophosphamide as a new preparative regimen for allogeneic haematopoietic stem cell transplantation in patients with an increased risk for regimen-related complications. Bone Marrow Transplant 2005;Feb35(3):233-41 (Pubitemid 40268293)
5. Gibbs JP, Czerwinski M, Slattery JT. Busulfan-glutathione conjugation catalyzed by human liver cytosolic glutathione S-transferases. Cancer Res 1996;Aug1556(16):3678-81 (Pubitemid 26272012)
6. Czerwinski M, Gibbs JP, Slattery JT. Busulfan conjugation by glutathione S-transferases alpha, mu, and pi. Drug Metab Dispos 1996;Sep24(9):1015-19 (Pubitemid 26314555)
7. Hassan M, Ehrsson H. Urinary metabolites of busulfan in the rat. Drug Metab Dispos 1987;May-Jun15(3):399-402 (Pubitemid 17096524)
8. Dunn CD. The chemical and biological properties of busulphan ("Myleran"). Exp Hematol 1974;2(3):101-17; Review
9. Tong WP, Ludlum DB. Crosslinking of DNA by busulfan. Formation of diguanyl derivatives. Biochim Biophys Acta 1980;Jun27608(1):174-81 (Pubitemid 10019597)
10. Bedford P, Fox BW. Repair of DNA interstrand crosslinks after busulphan. A possible mode of resistance. Cancer Chemother Pharmacol 1982;8(1):3-7
11. Ponti M, Souhami RL, Fox BW, Hartley JA. DNA interstrand crosslinking and sequence selectivity of dimethanesulphonates. Br J Cancer 1991;May63(5):743-7
12. Hartley JA, Fox BW. Cross-linking between histones and DNA following treatment with a series of dimethane sulphonate esters. Cancer Chemother Pharmacol 1986;17(1):56-62 (Pubitemid 16113827)
13. Marsh JC. The effects of cancer chemotherapeutic agents on normal hematopoietic precursor cells: a review. Cancer Res 1976;Jun36(6):1853-82
14. Hassan Z, Hassan M, Hellstrom-Lindberg E. The pharmacodynamic effect of busulfan in the P39 myeloid cell line in vitro. Leukemia 2001;Aug15(8):1240-7 (Pubitemid 32776448)
15. Santos GW, Tutschka PJ, Brookmeyer R, et al. Marrow transplantation for acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide. N Engl J Med 1983;Dec1309(22):1347-53 (Pubitemid 14246556)
16. Meng A, Wang Y, Van Zant G, Zhou D. Ionizing radiation and busulfan induce premature senescence in murine bone marrow hematopoietic cells. Cancer Res 2003;Sep163(17):5414-19 (Pubitemid 37139859)
17. Feit PW. Studies on epoxide formation from (2S,3S)-threitol 1, 4-bismethanesulfonate. The preparation and biological activity of (2S,3S)-1, 2-epoxy-3,4-butanediol 4-methanesulfonate. J Med Chem 1970;13(6):1173-5
18. Feit PW. 1,4-Bismethanesulfonates of the stereoisomeric butanetetraols and related compounds. J Med Chem 1964;7:14-17
19. Hartley JA, O'Hare CC, Baumgart J. DNA alkylation and interstrand cross-linking by treosulfan. Br J Cancer 1999;Jan79(2):264-6 (Pubitemid 29002295)
20. Werner S, Mendoza A, Hilger RA, et al. Preclinical studies of treosulfan demonstrate potent activity in Ewing's sarcoma. Cancer Chemother Pharmacol 2008;Jun62(1):19-31 (Pubitemid 351537841)
21. Munkelt D, Koehl U, Kloess S, et al. Cytotoxic effects of treosulfan and busulfan against leukemic cells of paediatric patients. Cancer Chemother Pharmacol 2008;Oct62(5):821-30
22. Down JD, Ploemacher RE. Transient and permanent engraftment potential of murine hematopoietic stem cell subsets: differential effects of host conditioning with gamma radiation and cytotoxic drugs. Exp Hematol 1993;Jul21(7):913-21 (Pubitemid 24215353)
23. Down JD, Boudewijn A, Dillingh JH, et al. Relationships between ablation of distinct haematopoietic cell subsets and the development of donor bone marrow engraftment following recipient pretreatment with different alkylating drugs. Br J Cancer 1994;Oct70(4):611-16 (Pubitemid 24305585)
24. Reynolds M, McCann SR. Sequential studies of bone marrow haemopoietic progenitors (CFU-GEM, BFU-E, CFU-E, CFU-GM) following busulfan treatment in Balb/c mice. J Immunopharmacol 1986;8(1):99-116 (Pubitemid 16101526)
25. Slattery JT, Sanders JE, Buckner CD, et al. Graft-rejection and toxicity following bone marrow transplantation in relation to busulfan pharmacokinetics. Bone Marrow Transplant 1995;Jul16(1):31-42
26. Leong LY, Qin S, Cobbold SP, Waldmann H. Classical transplantation tolerance in the adult: the interaction between myeloablation and immunosuppression. Eur J Immunol 1992;Nov22(11):2825-30
27. Santos GW, Tutschka PJ. Effect of busulfan on antibody production and skin allograft survival in the rat. J Natl Cancer Inst 1974;Dec53(6):1775-80
28. Jones R. New developments in cancer chemotherapeutic agents. Cancer Chemoth Rep. 1960;10:99
29. Kopf-Maier P, Sass G. Antitumor activity of treosulfan against human breast carcinomas. Cancer Chemother Pharmacol 1992;31(2):103-10
30. Kopf-Maier P. The alkylator treosulfan shows activity towards human renal-cell carcinoma in vivo and in vitro. In Vivo 1998;May-Jun12(3):275-88 (Pubitemid 28379988)
31. Neale MH, Myatt N, Cree IA, et al. Combination chemotherapy for choroidal melanoma: ex vivo sensitivity to treosulfan with gemcitabine or cytosine arabinoside. Br J Cancer 1999;Mar79(9-10):1487-93 (Pubitemid 29116809)
32. Neuber K, tom Dieck A, Blodorn-Schlicht N, et al. Treosulfan is an effective alkylating cytostatic for malignant melanoma in vitro and in vivo. Melanoma Res 1999;Apr9(2):125-32 (Pubitemid 29331520)
33. Ploemacher RE, Johnson KW, Rombouts EJ, et al. Addition of treosulfan to a nonmyeloablative conditioning regimen results in enhanced chimerism and immunologic tolerance in an experimental allogeneic bone marrow transplant model. Biol Blood Marrow Transplant 2004;Apr10(4):236-45 (Pubitemid 38456202)
34. Sender V, Hofmeister-Mielke N, Sievert K, et al. Preclinical analysis of treosulfan in combination with total body irradiation as conditioning regimen prior to bone marrow transplantation in rats. Immunopharmacol Immunotoxicol 2009;31(4):595-600
35. Westerhof GR, Ploemacher RE, Boudewijn A, et al. Comparison of different busulfan analogues for depletion of hematopoietic stem cells and promotion of donor-type chimerism in murine bone marrow transplant recipients. Cancer Res 2000;Oct160(19):5470-8
36. Lanvers-Kaminsky C, Bremer A, Dirksen U, et al. Cytotoxicity of treosulfan and busulfan on paediatric tumor cell lines. Anticancer Drugs 2006;17(6):657-62 (Pubitemid 44265866)
37. Fichtner I, Becker M, Baumgart J. Antileukaemic activity of treosulfan in xenografted human acute lymphoblastic leukaemias (ALL). Eur J Cancer 2003;Apr39(6):801-7 (Pubitemid 36315997)
38. Ciurea SO, Andersson BS. Busulfan in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2009;May15(5):523-36
39. Galton DA. The use of myleran and similar agents in chronic leukemias. Adv Cancer Res 1956;4:73-112
40. Tutschka PJ, Copelan EA, Klein JP. Bone marrow transplantation for leukemia following a new busulfan and cyclophosphamide regimen. Blood 1987;Nov70(5):1382-8 (Pubitemid 18026142)
41. Kim SE, Lee JH, Choi SJ, et al. Morbidity and non-relapse mortality after allogeneic bone marrow transplantation in adult leukemia patients conditioned with busulfan plus cyclophosphamide: a retrospective comparison of oral versus intravenous busulfan. Haematologica 2005;Feb90(2):285-6
42. Kashyap A, Wingard J, Cagnoni P, et al. Intravenous versus oral busulfan as part of a busulfan/Cyclophosphamide preparative regimen for allogeneic hematopoietic stem cell transplantation: decreased incidence of hepatic venoocclusive disease (HVOD), HVOD-related mortality, and overall 100-day mortality. Biol Blood Marrow Transplant 2002;8(9):493-500 (Pubitemid 35174823)
43. Aggarwal C, Gupta S, Vaughan WP, et al. Improved outcomes in intermediate-and high-risk aggressive non-Hodgkin lymphoma after autologous hematopoietic stem cell transplantation substituting intravenous for oral busulfan in a busulfan, cyclophosphamide, and etoposide preparative regimen. Biol Blood Marrow Transplant 2006;Jul12(7):770-7 (Pubitemid 43899416)
44. Dean RM, Pohlman B, Sweetenham JW, et al. Superior survival after replacing oral with intravenous busulfan in autologous stem cell transplantation for non-Hodgkin lymphoma with busulfan, cyclophosphamide and etoposide. Br J Haematol 2010;Jan148(2):226-34
45. Chae YS, Sohn SK, Kim JG, et al. New myeloablative conditioning regimen with fludarabine and busulfan for allogeneic stem cell transplantation: comparison with BuCy2. Bone Marrow Transplant 2007;Sep40(6):541-7 (Pubitemid 47382124)
46. Shimoni A, Shem-Tov N, Volchek Y, et al. Allo-SCT for AML and MDS with treosulfan compared with BU-based regimens: reduced toxicity vs reduced intensity. Bone Marrow Transplant 2012;47(10):1274-82
47. Bornhauser M, Storer B, Slattery JT, et al. Conditioning with fludarabine and targeted busulfan for transplantation of allogeneic hematopoietic stem cells. Blood 2003;Aug1102(3):820-6 (Pubitemid 36917770)
48. Gaziev J, Nguyen L, Puozzo C, et al. Novel pharmacokinetic behavior of intravenous busulfan in children with thalassemia undergoing hematopoietic stem cell transplantation: a prospective evaluation of pharmacokinetic and pharmacodynamic profile with therapeutic drug monitoring. Blood 2010;Jun3115(22):4597-604
49. Di Bartolomeo P, Santarone S, Di Bartolomeo E, et al. Long-term results of survival in patients with thalassemia major treated with bone marrow transplantation. Am J Hematol 2008;Jul83(7):528-30 (Pubitemid 351874867)
50. Resnick IB, Aker M, Tsirigotis P, et al. Allogeneic stem cell transplantation from matched related and unrelated donors in thalassemia major patients using a reduced toxicity fludarabine-based regimen. Bone Marrow Transplant 2007;Nov40(10):957-64 (Pubitemid 350048194)
51. Bredeson CN, Zhang MJ, Agovi MA, et al. Outcomes following HSCT using fludarabine, busulfan, and thymoglobulin: a matched comparison to allogeneic transplants conditioned with busulfan and cyclophosphamide. Biol Blood Marrow Transplant 2008;Sep14(9):993-1003
52. Russell JA, Tran HT, Quinlan D, et al. Once-daily intravenous busulfan given with fludarabine as conditioning for allogeneic stem cell transplantation: study of pharmacokinetics and early clinical outcomes. Biol Blood Marrow Transplant 2002;8(9):468-76 (Pubitemid 35174820)
53. 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 2007;Jan13(1):56-64 (Pubitemid 46044090)
54. 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;Jun14(6):672-84 (Pubitemid 351664062)
55. 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;Aug1104(3):857-64 (Pubitemid 38970585)
56. Santarone S, Pidala J, Di Nicola M, et al. Fludarabine and pharmacokinetic-targeted busulfan before allografting for adults with acute lymphoid leukemia. Biol Blood Marrow Transplant 2011;Oct17(10):1505-11
57. Pidala J, Roman-Diaz J, Kim J, et al. Targeted IV busulfan and fludarabine followed by post-allogeneic hematopoieticcell transplantation rituximab demonstrate encouraging activity in CD20+ lymphoid malignancies without increased risk of infectious complications. Int J Hematol 2011;Feb93(2):206-12
58. Shimoni A, Hardan I, Shem-Tov N, et al. Comparison between two fludarabine-based reduced-intensity conditioning regimens before allogeneic hematopoietic stem-cell transplantation: fludarabine/melphalan is associated with higher incidence of acute graft-versus-host disease and non-relapse mortality and lower incidence of relapse than fludarabine/busulfan. Leukemia 2007;21(10):2109-16 (Pubitemid 47423801)
59. Molina B, Alonso L, Gonzalez-Vicent M, et al. High-dose busulfan and melphalan as conditioning regimen for autologous peripheral blood progenitor cell transplantation in high-risk neuroblastoma patients. Pediatr Hematol Oncol 2011;Mar28(2):115-23
60. Carreras E, Bertz H, Arcese W, et al. Incidence and outcome of hepatic veno-occlusive disease after blood or marrow transplantation: a prospective cohort study of the European Group for Blood and Marrow Transplantation. European Group for Blood and Marrow Transplantation Chronic Leukemia Working Party. Blood 1998;92(10):3599-604 (Pubitemid 28525185)
61. Méresse V, Hartmann O, Vassal G, et al. Risk factors for hepatic veno-occlusive disease after high-dose busulfancontaining regimens followed by autologous bone marrow transplantation: a study in 136 children. Bone Marrow Transplant 1992;Aug10(2):135-41
62. Sadeghi B, Jansson M, Hassan Z, et al. The effect of administration order of BU and CY on engraftment and toxicity in HSCT mouse model. Bone Marrow Transplant 2008;May41(10):895-904 (Pubitemid 351761692)
63. Cantoni N, Gerull S, Heim D, et al. Order of application and liver toxicity in patients given BU and CY containing conditioning regimens for allogeneic hematopoietic SCT. Bone Marrow Transplant 2011;46(3):344-9
64. Hassan M, Ljungman P, Ringdén O, et al. The effect of busulphan on the pharmacokinetics of cyclophosphamide and its 4-hydroxy métabolite : time interval influence on therapeutic efficacy and therapy-related toxicity. Bone Marrow Transplant 2000;May25(9):915-24 (Pubitemid 30255722)
65. Bouligand J, Le Maitre A, Valteau-Co uanet D, et al. Elevated plasma ferritin and busulfan pharmacodynamics during high-dose chemotherapy regimens in children with malignant solid tumors. Clin Pharmacol Ther 2007;82(4):402-9 (Pubitemid 47414347)
66. Srivastava A, Poonkuzhali B, Shaji RV, et al. Glutathione S-transferase M1 polymorphism: a risk factor for hepatic venoocclusive disease in bone marrow transplantation. Blood 2004;Sep1104(5):1574-7 (Pubitemid 39166540)
67. Krivoy N, Hoffer E, Lurie Y, et al. Busulfan use in hematopoietic stem cell transplantation: pharmacology, dose adjustment, safety and efficacy in adults and children. Curr Drug Saf 2008;Jan3(1):60-6 (Pubitemid 351227235)
68. Kumar L, Raju GM, Ganessan K, et al. High dose chemotherapy followed by autologous haemopoietic stem cell transplant in multiple myeloma. Natl Med J India 2003;Jan-Feb16(1):16-21 (Pubitemid 36503232)
69. Grochow LB. Busulfan disposition: the role of therapeutic monitoring in bone marrow transplantation induction regimens. Semin Oncol 1993;Aug20(4 Suppl 4):18-25; quiz 26 (Pubitemid 23239401)
70. Grochow LB, Jones RJ, Brundrett RB, et al. Pharmacokinetics of busulfan: correlation with veno-occlusive disease in patients undergoing bone marrow transplantation. Cancer Chemother Pharmacol 1989;25(1):55-61 (Pubitemid 20000799)
71. Bartelink IH, Bredius RG, Belitser SV, et al. Association between busulfan exposure and outcome in children receiving intravenous busulfan before haematologic stem cell transplantation. Biol Blood Marrow Transplant 2009;Feb15(2):231-41
72. Bartelink IH, Bredius RG, Ververs TT, et al. Once-daily intravenous busulfan with therapeutic drug monitoring compared to conventional oral busulfan improves survival and engraftment in children undergoing allogeneic stem cell transplantation. Biol Blood Marrow Transplant 2008;Jan14(1):88-98 (Pubitemid 350286741)
73. Shaughnessy PJ, Ornstein D, Ririe D, et al. Phase II study of a moderate-intensity preparative regimen with allogeneic peripheral blood stem cell transplantation for haematologic diseases: the Texas Transplant Consortium experience. Biol Blood Marrow Transplant 2002;8(8):420-8
74. Kletzel M, Jacobsohn D, Duerst R. Pharmacokinetics of a test dose of intravenous busulfan guide dose modifications to achieve an optimal area under the curve of a single daily dose of intravenous busulfan in children undergoing a reduced-intensity conditioning regimen with hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2006;12(4):472-9 (Pubitemid 43380964)
75. McCune JS, Holmberg LA. Busulfan in hematopoietic stem cell transplant setting. Expert Opin Drug Metab Toxicol 2009;Aug5(8):957-69; Review
76. Eissner G, Multhoff G, Gerbitz A, et al. Fludarabine induces apoptosis, activation, and allogenicity in human endothelial and epithelial cells : protective effect of defibrotide. Blood 2002;Jul1100(1):334-40 (Pubitemid 35177465)
77. Vassal G, Deroussent A, Hartmann O, et al. Dose-dependent neurotoxicity of high-dose busulfan in children: a clinical and pharmacological study. Cancer Res 1990;Oct150(19):6203-7 (Pubitemid 20323675)
78. Hassan M, Ehrsson H, Smedmyr B, et al. Cerebrospinal fluid and plasma concentrations of busulfan during high-dose therapy. Bone Marrow Transplant 1989;Jan4(1):113-14 (Pubitemid 19064916)
79. Loeb V. Jr. Dihydroxybusulfan (NSC-39069) in chronic myelocytic leukemia and miscellaneous malignant neoplasms. Cancer Chemother Rep 1964;Nov42:39-43
80. Scheulen ME, Hilger RA, Oberhoff C, et al. Clinical phase I dose escalation and pharmacokinetic study of high-dose chemotherapy with treosulfan and autologous peripheral blood stem cell transplantation in patients with advanced malignancies. Clin Cancer Res 2000;Nov6(11):4209-16
81. Holowiecki J, Giebel S, Wojnar J, et al. Treosulfan and fludarabine low-toxicity conditioning for allogeneic haematopoietic stem cell transplantation in chronic myeloid leukaemia. Br J Haematol 2008;Jun142(2):284- 92 (Pubitemid 351987321)
82. Nemecek ER, Guthrie KA, Sorror ML, et al. Conditioning with treosulfan and fludarabine followed by allogeneic hematopoietic cell transplantation for high-risk haematologic malignancies. Biol Blood Marrow Transplant 2011;Mar17(3):341-50
83. Casper J, Wolff D, Knauf W, et al. Allogeneic hematopoietic stem-cell transplantation in patients with haematologic malignancies after dose-escalated treosulfan/fludarabine conditioning. J Clin Oncol 2010;Jul1028(20):3344-51
84. Wachowiak J, Sykora KW, Cornish J, EBMT Paediatric Diseases Working Party. Treosulfan-based preparative regimens for allo-HSCT in childhood haematological malignancies: a retrospective study on behalf of the EBMT paediatric diseases working party. Bone Marrow Transplant 2011;Dec46(12):1510-18
85. Slatter MA, Rao K, Amrolia P, et al. Treosulfan-based conditioning regimens for hematopoietic stem cell transplantation in children with primary immunodeficiency: united Kingdom experience. Blood 2011;Apr21117(16):4367-75
86. Główka FK, Romański M, Wachowiak J. High-dose treosulfan in conditioning prior to hematopoietic stem cell transplantation. Expert Opin Investig Drugs 2010;Oct19(10):1275-95; Review
87. Główka FK, Romański M, Tezyk A, et al. HPLC method for determination of biologically active epoxy-transformers of treosulfan in human plasma: pharmacokinetic application. J Pharm Biomed Anal 2012;Mar2562:105-13
88. Park S, Tretyakova N. Structural characterization of the major DNA-DNA cross-link of 1,2,3,4-diepoxybutane. Chem Res Toxicol 2004;Feb17(2):129-36 (Pubitemid 38252491)
89. Beelen DW, Trenschel R, Casper J, et al. Dose-escalated treosulphan in combination with cyclophosphamide as a new preparative regimen for allogeneic haematopoietic stem cell transplantation in patients with an increased risk for regimen-related complications. Bone Marrow Transplant 2005;Feb35(3):233-41 (Pubitemid 40268293)
90. Baronciani D, Rambaldi A, Iori AP, et al. Treosulfan/fludarabine as an allogeneic hematopoietic stem cell transplant conditioning regimen for high-risk patients. Am J Hematol 2008;Sep83(9):717-20
91. Shimoni A, Hardan I, Shem-Tov N, et al. Fludarabine and treosulfan: a novel modified myeloablative regimen for allogeneic hematopoietic stem-cell transplantation with effective antileukemia activity in patients with acute myeloid leukemia and myelodysplastic syndromes. Leuk Lymphoma 2007;Dec48(12):2352-9 (Pubitemid 350258301)
92. Greystoke B, Bonanomi S, Carr TF, et al. Treosulfan-containing regimens achieve high rates of engraftment associated with low transplant morbidity and mortality in children with non-malignant disease and significant co-morbidities. Br J Haematol 2008;Jun142(2):257-62 (Pubitemid 351987307)
93. Meissner B, Borkhardt A, Dilloo D, et al. Relapse, not regimen-related toxicity, was the major cause of treatment failure in 11 children with Down syndrome undergoing haematopoietic stem cell transplantation for acute leukaemia. Bone Marrow Transplant 2007;Nov40(10):945-9 (Pubitemid 350048192)
94. Ruutu T, Volin L, Beelen DW, et al. Reduced-toxicity conditioning with treosulfan and fludarabine in allogeneic hematopoietic stem cell transplantation for myelodysplastic syndromes: final results of an international prospective phase II trial. Haematologica 2011;Sep96(9):1344-50
95. Kashyap A, Wingard J, Cagnoni P, et al. Intravenous versus oral busulfan as part of a busulfan/cyclophosphamide preparative regimen for allogeneic hematopoietic stem cell transplantation: decreased incidence of hepatic veno-occlusive disease (HVOD), HVOD-related mortality, and overall 100-day mortality. Biol Blood Marrow Transplant 2002;8:493-500 (Pubitemid 35174823)
96. Andersson BS, Madden T, Tran HT, et al. Acute safety and pharmacokinetics of intravenous busulfan when used with oral busulfan and cyclophosphamide as pretransplantation conditioning therapy: a phase I study. Biol Blood Marrow Transplant 2000;6:548-54
97. Thall PF, Champlin RE, Andersson BS. Comparison of 100-day mortality rates associated with i.v. busulfan and cyclophosphamide vs other preparative regimens in allogeneic bone marrow transplantation for chronic myelogenous leukemia: Bayesian sensitivity analyses of confounded treatment and center effects. Bone Marrow Transplant 2004;33:1191-9 (Pubitemid 38961476)
98. Oechtering D, Schiltmeyer B, Hempel G, et al. Toxicity and pharmacokinetics of i.v. busulfan in children before stem cell transplantation. Anticancer Drugs 2005;16:337-44 (Pubitemid 40283950)
99. Zwaveling J, Bredius RGM, Cremers SCLM, et al. Intravenous busulfan in children prior to stem cell transplantation: study of pharmacokinetics in association with early clinical outcome and toxicity. Bone Marrow Transplant 2005;35:17-23 (Pubitemid 40090051)
100. McCune JS, Gooley T, Gibbs JP, et al. Busulfan concentration and graft rejection in paediatric patients undergoing hematopoietic stem cell transplantation. Bone Marrow Transplant 2002;30:167-73 (Pubitemid 34993856)
101. Bolinger AM, Zangwill AB, Slattery JT, et al. An evaluation of engraftment, toxicity and busulfan concentration in children receiving bone marrow transplantation for leukemia or genetic disease. Bone Marrow Transplant 2000;25:925-30 (Pubitemid 30255723)
102. Andersson BS, Thall PF, Madden T, et al. Busulfan systemic exposure relative to regimen-related toxicity and acute graft-versus-host disease: defining a therapeutic window for i.v. BuCy2 in chronic myelogenous leukemia. Biol Blood Marrow Transplant 2002;8:477-85 (Pubitemid 35174821)
103. Dix SP, Wingard JR, Mullins RE, et al. Association of Busulfan area under the curve with veno-occlusive disease following BMT. Bone Marrow Transplant 1996;17:225-30 (Pubitemid 26057312)
104. Grochow LB, Jones RJ, Brundrett RB, et al. Pharmacokinetics of Busulfan: correlation with veno-occlusive disease in patients undergoing bone marrow transplantation. Cancer Chemother Pharmacol 1989;25:61
105. Ljungman P, Hassan M, Bekassy AN, et al. High Busulfan concentrations are associated with increased transplant related mortality in allogeneic bone marrow transplant patients. Bone Marrow Transplant 1997;20:909-13 (Pubitemid 27510952)
106. Grochow LB. Busulfan disposition: the role of therapeutic monitoring in bone marrow transplantation induction regimens. Semin Oncol 1993;20:18-25 (Pubitemid 23239401)
107. Tran H, Petropoulos D, Worth L, et al. Pharmacokinetics and individualized dose adjustment of intravenous busulfan in children with advanced haematologic malignancies undergoing allogeneic stem cell transplantation. Biol Blood Marrow Transplant 2004;10:805-12 (Pubitemid 39406769)
108. Nguyen L. The impact of switching from oral to IV busulfan on haematopoietic stem cell transplantation. EJHPP Pract 2006;12:58-9
109. Leger F, Nguyen L, Puozzo C. Exposure equivalence between IV (0.8 mg/kg) and oral (1 mg/kg) Busulfan in adult patients. Eur J Clin Pharmacol 2009;65:903-11
110. Andersson BS, Kashyap A, Gian V, et al. Conditioning therapy with intravenous busulfan and cyclophosphamide (IV BuCy2) for haematologic malignancies prior to allogeneic stem cell transplantation: a phase II study. Biol Blood Marrow Transplant 2002;8:145-54 (Pubitemid 34285073)
111. Nguyen L, Leger F, Lennon S, Puozzo C. Intravenous busulfan in adults prior to haematopoietic stem cell transplantation: a population pharmacokinetic study. Cancer Chemother Pharmacol 2006;57:191-8 (Pubitemid 41779838)
112. Gibbs JP, Murray G, Risler L. Age-dependent tetrahydrothiophenium ion formation in young children and adults receiving high-dose busulfan. Cancer Res 1997;57:5509-16 (Pubitemid 28006757)
113. Bostrom B, Enockson K, Johnson A, et al. Plasma pharmacokinetics of high-dose oral busulfan in children and adults undergoing bone marrow transplantation. Pediatr Transplant 2003;7(Suppl 3):12-18 (Pubitemid 36314216)
114. Hassan M, Ljungman P, Bolme P, et al. Busulfan bioavailability. Blood 1994;84:2144-50 (Pubitemid 24296370)
115. Hassan M, Oberg G, Bekassy AN, et al. Pharmacokinetics of high-dose busulphan in relation to age and chronopharmacology. Cancer Chemother Pharmacol 1991;28:130-4
116. Gibbs JP, Liacouras CA, Baldassano RN, Slattery JT. Up-regulation of glutathione S-transferase activity in enterocytes of young children. Drug Metab Dispos 1999;27:1466-9
117. Nguyen L, Fuller D, Lennon S, et al. I. V. busulfan in paediatrics: a novel dosing to improve safety/efficacy for hematopoietic progenitor cell transplantation recipients. Bone Marrow Transplant 2004;33:979-87 (Pubitemid 38744783)
118. Vassal G, Michel G, Espérou H, et al. Prospective validation of a novel IV busulfan fixed dosing for paediatric patients to improve therapeutic AUC targeting without drug monitoring. Cancer Chemother Pharmacol 2008;61:113-23 (Pubitemid 47512633)
119. Michel G, Valteau-Couanet D, Gentet JC, et al. Weight-based strategy of dose administration in children using intravenous Busulfan: clinical and pharmacokinetic results. Pediatr Blood Cancer. 2012;58(1):90-7.
120. Paci A, Vassal G, Moshous D, et al. Pharmacokinetic behavior and appraisal of intravenous busulfan dosing in infants and older children: the results of a population pharmacokinetic study from a large paediatric cohort undergoing hematopoietic stem-cell transplantation. Ther Drug Monit 2012;Apr34(2):198-208
121. Główka FK, Karaźniewicz-Łada M, Grund G, et al. Pharmacokinetics of high-dose i.v. treosulfan in children undergoing treosulfan-based preparative regimen for allogeneic haematopoietic SCT. Bone Marrow Transplant 2008;Oct42(Suppl 2):S67-70; Review
122. Hilger RA, Harstrick A, Eberhardt W, et al. Clinical pharmacokinetics of intravenous treosulfan in patients with advanced solid tumors. Cancer Chemother Pharmacol 1998;42(2):99-104 (Pubitemid 28267289)
123. Gandhi V, Plunkett W. Cellular and clinical pharmacology of fludarabine. Clin Pharmacokinet 2002;41(2):93-103; Review (Pubitemid 34264036)
124. Russell JA, Irish W, Balogh A, et al. The addition of 400 cGY total body irradiation to a regimen incorporating once-daily intravenous busulfan, fludarabine, and antithymocyte globulin reduces relapse without affecting nonrelapse mortality in acute myelogenous leukemia. Biol Blood Marrow Transplant 2010;Apr16(4):509-14
125. Koenigsmann M, Mohren M, Jentsch-Ullrich K, et al. High-dose treosulfan in patients with relapsed or refractory high-grade lymphoma receiving tandem autologous blood stem cell transplantation. Bone Marrow Transplant 2004;Sep34(6):477-83 (Pubitemid 39264036)
126. Cutting R, Mirelman A, Vora A. Treosulphan as an alternative to busulphan for myeloablative conditioning in paediatric allogeneic transplantation. Br J Haematol 2008;Dec143(5):748-51