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Theoretical considerations and pharmacological data indicate that application of busulfan prior to subsequent cyclophosphamide (BuCy) may trigger liver toxicity. Reversing the order of application to cyclophosphamide-busulfan (CyBu) might be preferable, a hypothesis supported by animal data and retrospective studies. We performed a prospective randomized trial to determine impact of order of application of Bu and Cy before allo-HCT in 70 patients with hematological malignancy, 33 patients received BuCy and 37 CyBu for conditioning. In the short term, there were minimal differences in liver toxicity favoring CyBu over BuCy, significant only for alanine amino transferase at day 30 (<jats:italic>p<\/jats:italic> = 0.03). With longer follow-up at 4 years, non-relapse mortality (6% versus 27%, <jats:italic>p<\/jats:italic> = 0.05) was lower and survival (63% versus 43%, <jats:italic>p<\/jats:italic> = 0.06) was higher with CyBu compared to BuCy. Other outcomes, such as engraftment (<jats:italic>p<\/jats:italic> = 0.21), acute and chronic graft-versus-host disease (<jats:italic>p<\/jats:italic> = 0.40; 0.36), and relapse (<jats:italic>p<\/jats:italic> = 0.79), were similar in both groups. We prospectively show evidence that the order of application of Cy and Bu in myeloablative conditioning in allo-HCT patients has impact on outcome.<\/jats:p>","DOI":"10.1007\/s00277-020-04312-y","type":"journal-article","created":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T15:02:21Z","timestamp":1603465341000},"page":"209-216","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Busulfan-cyclophosphamide versus cyclophosphamide-busulfan as conditioning regimen before allogeneic hematopoietic cell transplantation: a prospective randomized trial"],"prefix":"10.1007","volume":"100","author":[{"given":"Claire","family":"Seydoux","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0427-7747","authenticated-orcid":false,"given":"Michael","family":"Medinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Gerull","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg","family":"Halter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Heim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Chalandon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stavroula Masouridi","family":"Levrat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urs","family":"Schanz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayathri","family":"Nair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Ansari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Simon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob R.","family":"Passweg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Cantoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,10,23]]},"reference":[{"issue":"13","key":"4312_CR1","doi-asserted-by":"publisher","first-page":"3569","DOI":"10.1182\/blood.V98.13.3569","volume":"98","author":"G Soci\u00e9","year":"2001","unstructured":"Soci\u00e9 G, Clift RA, Blaise D, Devergie A, Ringden O, Martin PJ et al (2001) Busulfan plus cyclophosphamide compared with total-body irradiation plus cyclophosphamide before marrow transplantation for myeloid leukemia: long-term follow-up of 4 randomized studies. 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