Recherche de facteurs de risque de toxicité du méthotrexate haute dose chez les patients adultes traités pour une hémopathie lymphoïde

Abstract : High-dose methotrexate (≥ 500 mg/m²) is widely used in the treatment of Acute Lymphoblastic Leukaemia and Non-Hodgkin Lymphoma. Despite measures encouraging methotrexate elimination (alkaline hydration) and preserving normal cells from its cytotoxic effects (leucovorin rescue), a large number of patients develop toxicity, which may be life-threatening. In this study, we investigated the incidence of renal, haematological and hepatic toxicities during 836 administrations of methotrexate to 321 adult patients treated for a lymphoid malignancy at Toulouse’s University Cancer Institute between 2014 and 2018. On review of the literature, there is currently no clearly identifiable risk factors which may increase the likelihood of methotrexate toxicity. Therefore, using collection and analysis of biologic and anthropometric data, our aim was to identify such markers. Our results demonstrate that grade ≥ 2 renal toxicity happened in 11,7% of methotrexate perfusions. Hypoalbuminemia, advanced age, overweight and good renal function were associated with nephrotoxicity risk. Haematological toxicity was seen in 14% of administrations and was independently correlated with hypoalbuminemia (OR = 2,53 ; CI95% [1,46 ; 4,63] ; p = 0,0015) and female gender (OR : 0,47 ; CI95% [0,28 ; 0,77] ; p = 0,0032). Grade ≥ 2 hepatotoxicity incidence was 37,2% (mostly hyperbilirubinemia) and was more likely to occur when there was evidence of renal toxicity in the same course (OR = 1,57 ; CI95% [1,04 ; 2,38] ; p = 0,033), treatment was for leukaemia rather than a lymphoma (OR = 1,69 ; CI95% [1,02 ; 2,82] ; p = 0,0433), and decreased with age (OR = 0,98 ; CI95% [0,97 ; 0,99] ; p = 0,0028). Amongst the patient risk factors which correlated with methotrexate toxicity, age, overweight and hypoalbuminemia seem relevant to consider for a dose adjustment on a case-by-case basis.
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Master Thesis
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Jean Gallot-Lavallée. Recherche de facteurs de risque de toxicité du méthotrexate haute dose chez les patients adultes traités pour une hémopathie lymphoïde. Sciences pharmaceutiques. 2019. ⟨dumas-02103420⟩

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