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Erschienen in:

28.05.2020 | Original Article

Busulfan clearance does not predict the development of hepatic veno-occlusive disease in patients undergoing hematopoietic stem cell transplantation

verfasst von: Bushra Salman, Murtadha Al-Khabori, Mohammed Al-Huneini, Abdulhakeem Al-Rawas, David Dennison, Mohammed Al-Za’abi

Erschienen in: International Journal of Hematology | Ausgabe 2/2020

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Abstract

Hepatic veno-occlusive disease (VOD) is a life-threatening complication following hematopoietic stem cell transplant (HSCT). Busulfan has a narrow therapeutic index and its concentration was found to correlate with VOD. Our primary objective was to assess the association between busulfan clearance and VOD in HSCT patients. In this retrospective analysis, we included patients who received their HSCT between 2003 and 2014 and followed at Sultan Qaboos University Hospital. All patients who received dose-targeted busulfan-containing conditioning were included. Target steady-state concentration (Css) was 800–900 ng/ml. VOD was assessed using modified Seattle criteria. The impact of busulfan clearance on VOD was analyzed using univariable logistic regression model. Seventy-three patients were included with a mean age of 15 years. Of those, 47% were transplanted for hematological malignancies and 53% for inherited hemoglobinopathies. Target Css was achieved in 85% of patients. The rate of VOD was 17%. There was no significant impact of busulfan clearance (p = 0.919) or area-under-the-concentration–time-curve (p = 0.275) on VOD. Targeting busulfan Css into narrow therapeutic range may have accounted for the findings. The risk of VOD might be related to other factors such as the genetic background, and more studies are required to investigate these factors.
Literatur
1.
Zurück zum Zitat Tran H, Petropoulos D, Worth L, Mullen CA, Madden T, Andersson B, Choroszy M, Nguyen J, Webb SK, Chan KW. Pharmacokinetics and individualized dose adjustment of intravenous busulfan in children with advanced hematologic malignancies undergoing allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2004;10:805–12.CrossRef Tran H, Petropoulos D, Worth L, Mullen CA, Madden T, Andersson B, Choroszy M, Nguyen J, Webb SK, Chan KW. Pharmacokinetics and individualized dose adjustment of intravenous busulfan in children with advanced hematologic malignancies undergoing allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2004;10:805–12.CrossRef
4.
Zurück zum Zitat Ciurea SO, Andersson BS. Busulfan in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2009;15:523–36.CrossRef Ciurea SO, Andersson BS. Busulfan in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2009;15:523–36.CrossRef
5.
Zurück zum Zitat Copelan EA. Transplantation hematopoietic stem-cell. N Engl J Med. 2006;354:1813–26.CrossRef Copelan EA. Transplantation hematopoietic stem-cell. N Engl J Med. 2006;354:1813–26.CrossRef
6.
Zurück zum Zitat Ten Brink MH, Zwaveling J, Swen JJ, et al. Personalized busulfan and treosulfan conditioning for pediatric stem cell transplantation: the role of pharmacogenetics and pharmacokinetics. Drug Discov Today. 2004;19(10):1572–86.CrossRef Ten Brink MH, Zwaveling J, Swen JJ, et al. Personalized busulfan and treosulfan conditioning for pediatric stem cell transplantation: the role of pharmacogenetics and pharmacokinetics. Drug Discov Today. 2004;19(10):1572–86.CrossRef
7.
Zurück zum Zitat Bacigalupo A, Ballen K, Rizzo D, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009;15(12):1628–33.CrossRef Bacigalupo A, Ballen K, Rizzo D, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009;15(12):1628–33.CrossRef
8.
Zurück zum Zitat dos Reis EO, Vianna-Jorge R, Suarez-Kurtz G, et al. Development of a rapid and specific assay for detection of busulfan in human plasma by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry. Rapid Commun Mass Spectrom. 2005;19:1666–744.CrossRef dos Reis EO, Vianna-Jorge R, Suarez-Kurtz G, et al. Development of a rapid and specific assay for detection of busulfan in human plasma by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry. Rapid Commun Mass Spectrom. 2005;19:1666–744.CrossRef
9.
Zurück zum Zitat Jambhekar SS, Breen PJ. Basic Pharmacokinetics. 2nd ed. London: The Pharmaceutical Press; 2012. Jambhekar SS, Breen PJ. Basic Pharmacokinetics. 2nd ed. London: The Pharmaceutical Press; 2012.
10.
Zurück zum Zitat Dalle JH, Giralt SA. Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: risk factors and stratification, prophylaxis, and treatment. Biol Blood Marrow Transplant. 2016;22:400–9.CrossRef Dalle JH, Giralt SA. Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: risk factors and stratification, prophylaxis, and treatment. Biol Blood Marrow Transplant. 2016;22:400–9.CrossRef
12.
Zurück zum Zitat Mohty M, Malard F, Abecassis M, Aerts E, Alaskar AS, Aljurf M, Arat M, Bader P, Baron F, Bazarbachi A, Blaise D, Ciceri F, Corbacioglu S, Dalle JH, Dignan F, Fukuda T, Huynh A, Masszi T, Michallet M, Nagler A, NiChonghaile M, Okamoto S, Pagliuca A, Peters C, Petersen FB, Richardson PG, Ruutu T, Savani BN, Wallhult E, Yakoub-Agha I, Duarte RF, Carreras E. Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a new classification from the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant. 2016;51(7):906–12.CrossRef Mohty M, Malard F, Abecassis M, Aerts E, Alaskar AS, Aljurf M, Arat M, Bader P, Baron F, Bazarbachi A, Blaise D, Ciceri F, Corbacioglu S, Dalle JH, Dignan F, Fukuda T, Huynh A, Masszi T, Michallet M, Nagler A, NiChonghaile M, Okamoto S, Pagliuca A, Peters C, Petersen FB, Richardson PG, Ruutu T, Savani BN, Wallhult E, Yakoub-Agha I, Duarte RF, Carreras E. Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a new classification from the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant. 2016;51(7):906–12.CrossRef
13.
Zurück zum Zitat Carreras E, Diaz Beya M, Rosinol L, Martínez C, Fernández-Avilés F, Rovira M. The incidence of veno-occlusive disease following allogeneic hematopoietic stem cell transplantation has diminished and outcome improved over the last decade. Biol Blood Marrow Transplant. 2011;17:1713–20.CrossRef Carreras E, Diaz Beya M, Rosinol L, Martínez C, Fernández-Avilés F, Rovira M. The incidence of veno-occlusive disease following allogeneic hematopoietic stem cell transplantation has diminished and outcome improved over the last decade. Biol Blood Marrow Transplant. 2011;17:1713–20.CrossRef
14.
Zurück zum Zitat Ryu SG, Lee JH, Choi SJ, Lee JH, Lee YS, Seol M, Hur EH, Lee SH, Bae KS, Noh GJ, Lee MS, Yun SC, Han SB, Lee KH. Randomized comparison of four-times-daily versus once-daily intravenous busulfan in conditioning therapy for hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2007;13:1095–105.CrossRef Ryu SG, Lee JH, Choi SJ, Lee JH, Lee YS, Seol M, Hur EH, Lee SH, Bae KS, Noh GJ, Lee MS, Yun SC, Han SB, Lee KH. Randomized comparison of four-times-daily versus once-daily intravenous busulfan in conditioning therapy for hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2007;13:1095–105.CrossRef
16.
Zurück zum Zitat Cappelli B, Cheisa R, Evangelio C, Biffi A, Roccia T, Frugnoli I, Biral E, Noè A, Fossati M, Finizio V, Miniero R, Napolitano S, Ferrua F, Soliman C, Ciceri F, Roncarolo MG, Marktel S. Absence of VOD in paediatric thalassaemic HSCT recipients using defibrotide prophylaxis and intravenous Busulphan. Br J Haematol. 2009;147(4):554–60.CrossRef Cappelli B, Cheisa R, Evangelio C, Biffi A, Roccia T, Frugnoli I, Biral E, Noè A, Fossati M, Finizio V, Miniero R, Napolitano S, Ferrua F, Soliman C, Ciceri F, Roncarolo MG, Marktel S. Absence of VOD in paediatric thalassaemic HSCT recipients using defibrotide prophylaxis and intravenous Busulphan. Br J Haematol. 2009;147(4):554–60.CrossRef
17.
Zurück zum Zitat Armand P, Kim HT, Cutler CS, Ho VT, Koreth J, Alyea EP, Soiffer RJ, Antin JH. Prognostic impact of elevated pretransplantation serum ferritin in patients undergoing myeloablative stem cell transplantation. Blood. 2007;109:4586–8.CrossRef Armand P, Kim HT, Cutler CS, Ho VT, Koreth J, Alyea EP, Soiffer RJ, Antin JH. Prognostic impact of elevated pretransplantation serum ferritin in patients undergoing myeloablative stem cell transplantation. Blood. 2007;109:4586–8.CrossRef
18.
Zurück zum Zitat Dennison JD, Muralitharan S, Tauro M, Zadjali S, Kindi SA, Macalalad ML. Permanent alopecia in children following busulfan based conditioning is associated with glutathione M1 null genotype. Blood. 2005;106:2740.CrossRef Dennison JD, Muralitharan S, Tauro M, Zadjali S, Kindi SA, Macalalad ML. Permanent alopecia in children following busulfan based conditioning is associated with glutathione M1 null genotype. Blood. 2005;106:2740.CrossRef
19.
Zurück zum Zitat Srivastava A, Poonkuzhali B, Shaji RV, George B, Mathews V, Chandy M, Krishnamoorthy R. Glutathione S-transferase M1 polymorphism: a risk factor for hepatic venoocclusive disease in bone marrow transplantation. Blood. 2004;104(5):1574–7.CrossRef Srivastava A, Poonkuzhali B, Shaji RV, George B, Mathews V, Chandy M, Krishnamoorthy R. Glutathione S-transferase M1 polymorphism: a risk factor for hepatic venoocclusive disease in bone marrow transplantation. Blood. 2004;104(5):1574–7.CrossRef
20.
Zurück zum Zitat Salman B, Al-Za'abi M, Al-Huneini M, et al. Therapeutic drug monitoring-guided dosing of busulfan differs from weight-based dosing in hematopoietic stem cell transplant patients. Hematol Oncol Stem Cell Ther. 2017;10(2):70–8.CrossRef Salman B, Al-Za'abi M, Al-Huneini M, et al. Therapeutic drug monitoring-guided dosing of busulfan differs from weight-based dosing in hematopoietic stem cell transplant patients. Hematol Oncol Stem Cell Ther. 2017;10(2):70–8.CrossRef
21.
Zurück zum Zitat Gyurkocza B, Sandmaier BM. Conditioning regimens for hematopoietic cell transplantation: one size does not fit all. Blood. 2014;124(3):344–53.CrossRef Gyurkocza B, Sandmaier BM. Conditioning regimens for hematopoietic cell transplantation: one size does not fit all. Blood. 2014;124(3):344–53.CrossRef
22.
Zurück zum Zitat Michel G, Valteau-Couanet D, Gentet JC, Esperou H, Socié G, Méchinaud F, Doz F, Neven B, Bertrand Y, Galambrun C, Demeocq F, Yakouben K, Bordigoni P, Frappaz D, Nguyen L, Vassal G. Weight-based strategy of dose administration in children using intravenous busulfan: clinical and pharmacokinetic results. Pediatr Blood Cancer. 2012;58(1):90–7.CrossRef Michel G, Valteau-Couanet D, Gentet JC, Esperou H, Socié G, Méchinaud F, Doz F, Neven B, Bertrand Y, Galambrun C, Demeocq F, Yakouben K, Bordigoni P, Frappaz D, Nguyen L, Vassal G. Weight-based strategy of dose administration in children using intravenous busulfan: clinical and pharmacokinetic results. Pediatr Blood Cancer. 2012;58(1):90–7.CrossRef
Metadaten
Titel
Busulfan clearance does not predict the development of hepatic veno-occlusive disease in patients undergoing hematopoietic stem cell transplantation
verfasst von
Bushra Salman
Murtadha Al-Khabori
Mohammed Al-Huneini
Abdulhakeem Al-Rawas
David Dennison
Mohammed Al-Za’abi
Publikationsdatum
28.05.2020
Verlag
Springer Singapore
Erschienen in
International Journal of Hematology / Ausgabe 2/2020
Print ISSN: 0925-5710
Elektronische ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-020-02891-0

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