• Radha Ramanan, Andrew B M Lim, Joanne L C Tan, Rahul D Barmanray, Kate Mason, Jenny Collins, Matthew Hillman, Jeff Szer, Ashish Bajel, and David Ritchie.
• Department of Clinical Haematology, Peter MacCallum Cancer Centre and The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
• Intern Med J. 2023 Jun 1; 53 (6): 951960951-960.

BackgroundConcern regarding dose-related toxicities of methotrexate (MTX) and cyclosporin (CYA) graft-versus-host disease (GVHD) prophylaxis occasionally leads to dose alterations post allogeneic haemopoietic cell transplant (alloHCT).AimsTo clarify causes of MTX and CYA dose alteration and assess impact on patient outcomes, including GVHD, relapse, non-relapse mortality (NRM) and overall survival (OS).MethodsAnalysis 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-rank 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-transplant variables and MTX alteration. Multivariate models for OS and NRM were constructed using Cox proportional hazards modelling and competing risk regression respectively.ResultsFifty-four (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; P = <0.001) and higher NRM (odds ratio (OR) 4.6; P < 0.001) at 6 years post-landmark. CYA alteration was associated with greater NRM (OR 2.7; P = 0.0137) at 6 years. GVHD rates were unaffected by dose alteration.ConclusionsOur 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.© 2022 Royal Australasian College of Physicians.

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