Top

Supportive Care in Cancer

Published in:

Open Access 01-12-2015 | Original Article

Economic and clinical aspects of intravenous versus oral busulfan in adult patients for conditioning prior to HSCT

Authors: Karin Berger, Dorothee Schopohl, Christina Rieger, Helmut Ostermann

Published in: Supportive Care in Cancer | Issue 12/2015

Abstract

Purpose

Busulfan (BU) used as cytoreductive conditioning prior to hematopoietic stem cell transplantation (HSCT) is available as intravenous (IV) and oral (O) preparation. IV-BU has clinical advantages associated with relevant incremental costs. The aim was to determine the economic impact of IV-BU versus O-BU in adult HSCT recipients from a German health care providers’ perspective.

Methods

A budget-impact model (BIM) including costs and risks for oral mucositis (OM), infection with OM, and hepatic sinusoidal obstruction syndrome (SOS) was developed. Model inputs are literature data comparing clinical effects of IV-BU versus O-BU and German cost data (conditioning therapy, treatment of OM, infections, SOS without/with multiorgan failure) from literature and tariff lists.

Results

Base case calculations resulted the following: total costs of adverse events were €86,434 with O-BU and €44,376 with IV-BU for ten patients each. Considering costs of adverse events and drugs, about €5840 for ten patients receiving IV-BU are saved. Sensitivity analyses were conducted in several ways. Cost savings range between €4910 and €12,640 per ten patients for all adverse events and €2070 or €1140 per ten patients considering SOS only. Drug treatment of SOS and treatment of multiorgan failure during severe SOS are major cost drivers. Worst case scenario calculations (assuming −25 % risk of all adverse events for O-BU and +25 % for IV-BU) yield up to €27,570 per ten patients with IV-BU.

Conclusions

Considering costs of adverse events and drugs, IV-BU is the dominant alternative from a German providers’ perspective. For more comprehensive economic evaluations, additional epidemiological data, evidence on clinical outcomes, patient-reported outcomes, and treatment patterns are needed.

Passweg JR, Baldomero H, Bregni M, Cesaro S, Dreger P, Duarte RF, Falkenburg JH, Kroger N, Farge-Bancel D, Gaspar HB, Marsh J, Mohty M, Peters C, Sureda A, Velardi A, Ruiz de Elvira C, Madrigal A (2013) Hematopoietic SCT in Europe: data and trends in 2011. Bone Marrow Transplant 48(9):1161–1167. doi:10.1038/bmt.2013.51 PubMedCentralCrossRefPubMed

Jahresbericht (2012) DRST Deutsches Register für Stammzelltransplantationen. http://www.drstde/download/jb2012pdf. Accessed 01 Mar 2014

Parmar S, Rondon G, de Lima M, Thall P, Bassett R, Anderlini P, Kebriaei P, Khouri I, Ganesan P, Champlin R, Giralt S (2013) Dose intensification of busulfan in the preparative regimen is associated with improved survival: a phase I/II controlled, randomized study. Biol Blood Marrow Transplant 19(3):474–480. doi:10.1016/j.bbmt.2012.12.001 PubMedCentralCrossRefPubMed

Bredeson C, LeRademacher J, Kato K, Dipersio JF, Agura E, Devine SM, Appelbaum FR, Tomblyn MR, Laport GG, Zhu X, McCarthy PL, Ho VT, Cooke KR, Armstrong E, Smith A, Rizzo JD, Burkart JM, Pasquini MC (2013) Prospective cohort study comparing intravenous busulfan to total body irradiation in hematopoietic cell transplantation. Blood 122(24):3871–3878. doi:10.1182/blood-2013-08-519009 PubMedCentralCrossRefPubMed

Ciurea SO, Andersson BS (2009) Busulfan in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 15(5):523–536. doi:10.1016/j.bbmt.2008.12.489 PubMedCentralCrossRefPubMed

Copelan EA, Hamilton BK, Avalos B, Ahn KW, Bolwell BJ, Zhu X, Aljurf M, van Besien K, Bredeson C, Cahn JY, Costa LJ, de Lima M, Gale RP, Hale GA, Halter J, Hamadani M, Inamoto Y, Kamble RT, Litzow MR, Loren AW, Marks DI, Olavarria E, Roy V, Sabloff M, Savani BN, Seftel M, Schouten HC, Ustun C, Waller EK, Weisdorf DJ, Wirk B, Horowitz MM, Arora M, Szer J, Cortes J, Kalaycio ME, Maziarz RT, Saber W (2013) Better leukemia-free and overall survival in AML in first remission following cyclophosphamide in combination with busulfan compared with TBI. Blood 122(24):3863–3870. doi:10.1182/blood-2013-07-514448 PubMedCentralCrossRefPubMed

Nath CE, Shaw PJ (2007) Busulphan in blood and marrow transplantation: dose, route, frequency and role of therapeutic drug monitoring. Curr Clin Pharmacol 2(1):75–91CrossRefPubMed

Aggarwal C, Gupta S, Vaughan WP, Saylors GB, Salzman DE, Katz RO, Nance AG, Tilden AB, Carabasi MH (2006) 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 12(7):770–777. doi:10.1016/j.bbmt.2006.03.016 CrossRefPubMed

Dean RM, Pohlman B, Sweetenham JW, Sobecks RM, Kalaycio ME, Smith SD, Copelan EA, Andresen S, Rybicki LA, Curtis J, Bolwell BJ (2010) 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 148(2):226–234. doi:10.1111/j.1365-2141.2009.07940.x CrossRefPubMed

10.

Ferrara F, Mele G, Palmieri S, Pedata M, Copia C, Riccardi C, Izzo T, Criscuolo C, Musto P (2009) Continuous infusion idarubicin and intravenous busulphan as conditioning regimen to autologous stem cell transplantation for patients with acute myeloid leukaemia. Hematol Oncol 27(4):198–202. doi:10.1002/hon.903 CrossRefPubMed

11.

Kashyap A, Wingard J, Cagnoni P, Roy J, Tarantolo S, Hu W, Blume K, Niland J, Palmer JM, Vaughan W, Fernandez H, Champlin R, Forman S, Andersson BS (2002) 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 8(9):493–500CrossRefPubMed

12.

Kim SE, Lee JH, Choi SJ, Ryu SG, Lee KH (2005) 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 90(2):285–286PubMed

13.

Lee JH, Choi SJ, Kim SE, Park CJ, Chi HS, Lee MS, Lee JS, Kim WK, Lee KH (2005) Decreased incidence of hepatic veno-occlusive disease and fewer hemostatic derangements associated with intravenous busulfan vs oral busulfan in adults conditioned with busulfan + cyclophosphamide for allogeneic bone marrow transplantation. Ann Hematol 84(5):321–330. doi:10.1007/s00277-004-0982-4 CrossRefPubMed

14.

Sobecks RM, Rybicki L, Yurch M, Kalaycio M, Dean R, Andresen S, Pohlman B, Duong H, Bolwell B, Copelan E (2012) Intravenous compared with oral busulfan as preparation for allogeneic hematopoietic progenitor cell transplantation for AML and MDS. Bone Marrow Transplant 47(5):633–638. doi:10.1038/bmt.2011.167 CrossRefPubMed

15.

InEK Institut für das Entgeltsystem im Krankenhaus GmbH, G-DRG-Fallpauschalen-Katalog 2014. http://www.g-drgde/cms/G-DRG-System_2014/Fallpauschalen-Katalog/Fallpauschalen-Katalog_2014. Accessed 29 Jan 2014

16.

Timothy W, Smith BA, Jonothan C, Tierce C Designing and developing budget impact models suited for global adaption (summary of a workshop given at the ISPOR 10th Annual International Meeting, May 16, 2005, Washington DC, USA). http://www.ispororg/news/articles/aug06/designingasp. Accessed 27 Jan 2014

17.

Mauskopf JA, Sullivan SD, Annemans L, Caro J, Mullins CD, Nuijten M, Orlewska E, Watkins J, Trueman P (2007) Principles of good practice for budget impact analysis: report of the ISPOR Task Force on good research practices—budget impact analysis. Value Health 10(5):336–347. doi:10.1111/j.1524-4733.2007.00187.x CrossRefPubMed

18.

Coppell JA, Richardson PG, Soiffer R, Martin PL, Kernan NA, Chen A, Guinan E, Vogelsang G, Krishnan A, Giralt S, Revta C, Carreau NA, Iacobelli M, Carreras E, Ruutu T, Barbui T, Antin JH, Niederwieser D (2010) Hepatic veno-occlusive disease following stem cell transplantation: incidence, clinical course, and outcome. Biol Blood Marrow Transplant 16(2):157–168. doi:10.1016/j.bbmt.2009.08.024 PubMedCentralCrossRefPubMed

19.

Elting LS, Cooksley C, Chambers M, Cantor SB, Manzullo E, Rubenstein EB (2003) The burdens of cancer therapy. Clinical and economic outcomes of chemotherapy-induced mucositis. Cancer 98(7):1531–1539. doi:10.1002/cncr.11671 CrossRefPubMed

20.

Banz K, Bischoff H, Brunner M, Chouaid C, de Castro Carpeno J, de Marinis F, Grossi F, Vergnenegre A, Walzer S (2011) Comparison of treatment costs of grade 3/4 adverse events associated with erlotinib or pemetrexed maintenance therapy for patients with advanced non-small-cell lung cancer (NSCLC) in Germany, France, Italy, and Spain. Lung Cancer 74(3):529–534. doi:10.1016/j.lungcan.2011.04.010 CrossRefPubMed

21.

Moerer O, Schmid A, Hofmann M, Herklotz A, Reinhart K, Werdan K, Schneider H, Burchardi H (2002) Direct costs of severe sepsis in three German intensive care units based on retrospective electronic patient record analysis of resource use. Intensive Care Med 28(10):1440–1446. doi:10.1007/s00134-002-1429-9 CrossRefPubMed

22.

Paessens BJ, von Schilling C, Berger K, Shlaen M, Muller-Thomas C, Bernard R, Peschel C, Ihbe-Heffinger A (2011) Health resource consumption and costs attributable to chemotherapy-induced toxicity in German routine hospital care in lymphoproliferative disorder and NSCLC patients. Ann Oncol 22(10):2310–2319. doi:10.1093/annonc/mdq759 CrossRefPubMed

23.

Richardson PG, Soiffer RJ, Antin JH, Uno H, Jin Z, Kurtzberg J, Martin PL, Steinbach G, Murray KF, Vogelsang GB, Chen AR, Krishnan A, Kernan NA, Avigan DE, Spitzer TR, Shulman HM, Di Salvo DN, Revta C, Warren D, Momtaz P, Bradwin G, Wei LJ, Iacobelli M, McDonald GB, Guinan EC (2010) Defibrotide for the treatment of severe hepatic veno-occlusive disease and multiorgan failure after stem cell transplantation: a multicenter, randomized, dose-finding trial. Biol Blood Marrow Transplant 16(7):1005–1017. doi:10.1016/j.bbmt.2010.02.009 PubMedCentralCrossRefPubMed

24.

NUB Antrag 2012/2013 Defibrotide i.v. http://www.kinderkrebsinfode/sites/kinderkrebsinfo/content/e2260/e5888/e84884/e84885/e113489/2013_GPOH_Defibrotide04102012_gerpdf. Accessed 29 Jan 2014

25.

Lauer-Fischer Lauer-Taxe® (2013) http://www.2lauer-fischer.de/produkte/arzneimitteldaten-online/webapo-infosystem/. Accessed 01 Mar 2014

26.

Dignan FL, Wynn RF, Hadzic N, Karani J, Quaglia A, Pagliuca A, Veys P, Potter MN (2013) BCSH/BSBMT guideline: diagnosis and management of veno-occlusive disease (sinusoidal obstruction syndrome) following haematopoietic stem cell transplantation. Br J Haematol 163(4):444–457. doi:10.1111/bjh.12558 CrossRefPubMed

27.

Graf von der Schulenburg JM, Greiner W, Jost F, Klusen N, Kubin M, Leidl R, Mittendorf T, Rebscher H, Schoeffski O, Vauth C, Volmer T, Wahler S, Wasem J, Weber C (2008) German recommendations on health economic evaluation: third and updated version of the Hanover Consensus. Value Health 11(4):539–544. doi:10.1111/j.1524-4733.2007.00301.x CrossRefPubMed

28.

Centre for Evidence-Based Medicine: Number Needed to Treat (NNT). http://www.cebmnet/number-needed-to-treat-nnt/. Accessed Sep 18 2014

29.

Lee SJ, Klar N, Weeks JC, Antin JH (2000) Predicting costs of stem-cell transplantation. J Clin Oncol 18(1):64–71PubMed

30.

Esperou H, Myon E, Robin M, Chadelat C, Ferry C, Devergie A, Ribaud P, Rocha V, Socié G, Gluckman E Cost-assessment of conditioning regiment in allogeneic haematopoetic stem cell transplantation using IV busulfan (Busilvex) versus oral busulfan: a French model; 31st Annual Meeting of the European Group for Blood and Marrow Transplantation 2005. http://registration.akm.ch/einsichtphp?XNABSTRACT_ID=5305&XNSPRACHE_ID=2&XNKONGRESS_ID=12&XNMASKEN_ID=900. Accessed 24 Feb 2014

31.

Tellez Giron G, Salgado JL, Soto H (2012) Cost effectiveness analysis of busulfan–cyclophosphamide (BuCy2) as conditioning regimen before allogeneic human stem cell transplantation (HSCT): comparison of oral versus IV busulfan. Value Health 15(4):A220CrossRef

32.

Barr RD (2012) Economic evaluation of hematopoietic stem cell transplantation. Hematology 17(Suppl 1):S198–S201. doi:10.1179/102453312X13336169157176 PubMed

33.

Zhang H, Graiser M, Hutcherson DA, Dada MO, McMillan S, Ali Z, Flowers CR, Waller EK (2012) Pharmacokinetic-directed high-dose busulfan combined with cyclophosphamide and etoposide results in predictable drug levels and durable long-term survival in lymphoma patients undergoing autologous stem cell transplantation. Biol Blood Marrow Transplant 18(8):1287–1294. doi:10.1016/j.bbmt.2012.02.006 CrossRefPubMed

34.

Lim ZY, Thanigaikumar M, Gandhi S, Pearce L, Kenyon M, Ho AYL, Devereux S, Pagliuca A, Mufti GJ (2007) Use of intravenous busulphan for reduced intensity conditioning (RIC) haematopoietic stem cell transplantation (HSCT) is associated with delayed T-cell full donor chimerism and lower incidence of acute graft versus host disease. Blood (ASH Annual Meeting Abstracts) 110 (Abstract 1994)

35.

Pavletic SZ, Fowler DH (2012) Are we making progress in GVHD prophylaxis and treatment? Hematol Am Soc Hematol Educ Program 2012:251–264. doi:10.1182/asheducation-2012.1.251

Title: Economic and clinical aspects of intravenous versus oral busulfan in adult patients for conditioning prior to HSCT
Authors: Karin Berger
Dorothee Schopohl
Christina Rieger
Helmut Ostermann
Publication date: 01-12-2015
Publisher: Springer Berlin Heidelberg
Published in: Supportive Care in Cancer / Issue 12/2015
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI: https://doi.org/10.1007/s00520-015-2695-8

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 12/2015

What bothers lung cancer patients the most? A prospective, longitudinal electronic patient-reported outcomes study in advanced non-small cell lung cancer

Knowledge and attitudes of Brazilian dental students and dentists regarding bisphosphonate-related osteonecrosis of the jaw

Fertility preservation in young cancer patients—too little, too late?

Burden of spousal caregivers of stage II and III esophageal cancer survivors 3 years after treatment with curative intent

Clinical efficacy of denosumab versus bisphosphonates for the prevention of bone complications: implications for nursing

Difficult choices for young patients with cancer: the supportive role of decisional counseling

Keynote webinar | Spotlight on antibody–drug conjugates in cancer