Treosulfan Metabolite (S, S-EBDM) Pharmacokinetics Influences Regimen Related Toxicity in Patients with Beta Thalassaemia Major Undergoing HSCT

PAI, Aswin Anand ; Panetta, John C ; Mohanan, Ezhil Pavai ; Illangeswaran, Raveen Stephen Stallon ; Balakrishnan, Balaji ; Edison, Eunice Sindhuvi ; Lakshmi, Kavitha M ; Kulkarni, Uday Prakash ; Devasia, Anup Joseph ; N., Fouzia ; Korula, Anu ; Abraham, Aby ; George, Biju ; Mathews, Vikram ; Srivastava, Alok ; Balasubramanian, Poonkuzhali (2019) Treosulfan Metabolite (S, S-EBDM) Pharmacokinetics Influences Regimen Related Toxicity in Patients with Beta Thalassaemia Major Undergoing HSCT Blood, 134 (Supple). p. 1977. ISSN 0006-4971

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Official URL: http://doi.org/10.1182/blood-2019-125604

Related URL: http://dx.doi.org/10.1182/blood-2019-125604

Abstract

A toxicity reduced conditioning regimen containing Treosulfan (Treo), Fludarabine (Flu), Thiotepa in patients with class III high risk thalassemia major (TM) has significantly improved transplant outcomes compared to the historical Busulfan/cyclophosphamide based myeloablative regimen (Mathews et al, 2013). However, complications related to mixed chimerism, rejection and regimen related toxicity remain. Analysis of Treo pharmacokinetics (PK) in TM showed significant inter individual variation but no association with HSCT outcome (Mohanan et al, 2018). This may be attributed to the fact that only the pro-drug Treo was measured and not its active metabolites. Treo, administered as a prodrug, is converted non-enzymatically to its active metabolite monoepoxide 2S, 3S-1,2-epoxybutane-3,4-diol-4-methanesulfonate (S, S-EBDM) and (2S,3S)- 1,2:3,4-diepoxybutane (S, S-DEB) that causes cytotoxicity. We have now assessed the PK of both Treo and S, S-EBDM and the factors which may influence the inter-individual variation in PK, and their impact on HSCT outcome in patients with TM.

Item Type:Article
Source:Copyright of this article belongs to The American Society of Hematology.
ID Code:124115
Deposited On:04 Nov 2021 05:55
Last Modified:04 Nov 2021 05:55

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