{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:18:16Z","timestamp":1747185496485,"version":"3.40.5"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T00:00:00Z","timestamp":1662422400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Internal Medicine Journal"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Concern regarding dose\u2010related toxicities of methotrexate (MTX) and cyclosporin (CYA) graft\u2010versus\u2010host disease (GVHD) prophylaxis occasionally leads to dose alterations post allogeneic haemopoietic cell transplant (alloHCT).<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To clarify causes of MTX and CYA dose alteration and assess impact on patient outcomes, including GVHD, relapse, non\u2010relapse mortality (NRM) and overall survival (OS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Analysis of retrospective data was performed in a single tertiary centre of patients who underwent alloHCT for any indication and who received GVHD prophylaxis with CYA and MTX between the years 2011 and 2015. Univariate analysis was conducted using the log\u2010rank test for OS and using competing risk regression for NRM, relapse and GVHD. Fisher exact tests were used to determine if an association existed between each of the pre\u2010transplant variables and MTX alteration. Multivariate models for OS and NRM were constructed using Cox proportional hazards modelling and competing risk regression respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fifty\u2010four (28%) of 196 had MTX alterations and 61\/187 (33%) had CYA alterations. Reasons for MTX alteration included mucositis, renal or liver impairment, fluid overload and sepsis. Causes of CYA alteration were numerous, but most commonly due to acute kidney impairment. MTX alteration was associated with inferior OS (hazard ratio 2.4; <jats:italic>P<\/jats:italic> = &lt;0.001) and higher NRM (odds ratio (OR) 4.6; <jats:italic>P<\/jats:italic> &lt;\u20090.001) at 6\u2009years post\u2010landmark. CYA alteration was associated with greater NRM (OR 2.7; <jats:italic>P<\/jats:italic> =\u20090.0137) at 6\u2009years. GVHD rates were unaffected by dose alteration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings suggest dose alteration in MTX and CYA GVHD prophylaxis is associated with adverse survival outcomes in alloHCT, without a significant impact on GVHD rates.<\/jats:p><\/jats:sec>","DOI":"10.1111\/imj.15829","type":"journal-article","created":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T14:30:51Z","timestamp":1654525851000},"page":"951-960","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Predictors and outcomes of dose reduction of methotrexate and cyclosporin <scp>graft\u2010versus\u2010host disease<\/scp> prophylaxis following allogeneic haemopoietic cell transplantation"],"prefix":"10.1111","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5539-0673","authenticated-orcid":false,"given":"Radha","family":"Ramanan","sequence":"first","affiliation":[{"name":"Department of Clinical Haematology Peter MacCallum Cancer Centre and The Royal Melbourne Hospital  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5751-6900","authenticated-orcid":false,"given":"Andrew B. M.","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Clinical Haematology and Olivia Newton John Cancer Research Institute Austin Health  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanne L. C.","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Haematology Alfred Health  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1433-2239","authenticated-orcid":false,"given":"Rahul D.","family":"Barmanray","sequence":"additional","affiliation":[{"name":"Department of Medicine, Dentistry and Health Sciences The University of Melbourne  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kate","family":"Mason","sequence":"additional","affiliation":[{"name":"Department of Clinical Haematology and Olivia Newton John Cancer Research Institute Austin Health  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny","family":"Collins","sequence":"additional","affiliation":[{"name":"Department of Clinical Haematology Peter MacCallum Cancer Centre and The Royal Melbourne Hospital  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Hillman","sequence":"additional","affiliation":[{"name":"Department of Clinical Haematology Peter MacCallum Cancer Centre and The Royal Melbourne Hospital  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6783-2301","authenticated-orcid":false,"given":"Jeff","family":"Szer","sequence":"additional","affiliation":[{"name":"Department of Clinical Haematology Peter MacCallum Cancer Centre and The Royal Melbourne Hospital  Melbourne Victoria Australia"},{"name":"Department of Medicine, Dentistry and Health Sciences The University of Melbourne  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashish","family":"Bajel","sequence":"additional","affiliation":[{"name":"Department of Clinical Haematology Peter MacCallum Cancer Centre and The Royal Melbourne Hospital  Melbourne Victoria Australia"},{"name":"Sir Peter MacCallum Department of Oncology University of Melbourne  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Ritchie","sequence":"additional","affiliation":[{"name":"Department of Clinical Haematology Peter MacCallum Cancer Centre and The Royal Melbourne Hospital  Melbourne Victoria Australia"},{"name":"Department of Medicine, Dentistry and Health Sciences The University of Melbourne  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,9,6]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V67.4.1172.1172"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hon.716"},{"key":"e_1_2_6_4_1","first-page":"1720","article-title":"Influence of acute and chronic graft\u2010versus\u2010host disease on relapse and survival after bone marrow transplantation from 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allo\u2010BMT","volume":"48","author":"Honda A","year":"2013","journal-title":"Bone"},{"key":"e_1_2_6_13_1","first-page":"161","article-title":"Omission of day +11 methotrexate after allogeneic bone marrow transplantation is associated with increased risk of severe acute graft\u2010versus\u2010host disease","volume":"30","author":"Kumar S","year":"2002","journal-title":"Bone"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19990515)85:10<2103::AID-CNCR2>3.0.CO;2-0"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21979"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1214\/aos\/1176350951"},{"key":"e_1_2_6_17_1","unstructured":"CheeL TaceyM LimB RitchieD.Serum ferritin is independent of disease risk index for overall survival following allogeneic stem cell transplantation. 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